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Issue 32, August 9, 2022

CDC Science Clips: Volume 14, Issue 32, August 9, 2022

This week, Science Clips is pleased to feature articles related to the new CDC Vital Signs Too Few People Treated for Hepatitis C: Reducing Barriers Can Increase Treatment and Save Lives

Over 2 million adults in the United States have hepatitis C virus (HCV) infection, and new infections have continued to rise. Hepatitis C is usually spread through blood, often from injection drug use. Left untreated, hepatitis C can cause advanced liver disease, liver cancer, and death. In 2019, hepatitis C contributed to the deaths of more than 14,200 people in the United States; deaths associated with hepatitis C were higher for Black people (5 per 100,000) and Hispanic people (4 per 100,000) than for White people (3 per 100,000).

Hepatitis C is curable in more than 95% of cases. People who test positive for hepatitis C should be treated with direct-acting antiviral (DAA) medication. Timely treatment is important to prevent liver damage and further spread. Treatment saves lives, prevents ongoing spread, and can save costs by stopping the disease from progressing.

Expanding treatment for all people with hepatitis C is essential to reducing viral hepatitis-related disparities and eliminating hepatitis C as a national public health threat.

  1. CDC Vital Signs
    • Too Few People Treated for Hepatitis C
      1. Hepatitis B and C cause most cases of hepatitis in the United States and the world. The two diseases account for about a million deaths a year and 78 percent of world's hepatocellular carcinoma and more than half of all fatal cirrhosis. In 2013 viral hepatitis, of which hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common types, surpassed HIV and AIDS to become the seventh leading cause of death worldwide. The world now has the tools to prevent hepatitis B and cure hepatitis C. Perfect vaccination could eradicate HBV, but it would take two generations at least. In the meantime, there is no cure for the millions of people already infected. Conversely, there is no vaccine for HCV, but new direct-acting antivirals can cure 95 percent of chronic infections, though these drugs are unlikely to reach all chronically-infected people anytime soon. This report, the second of two, builds off the conclusions of the first report and outlines a strategy for hepatitis reduction over time and specific actions to achieve them.

      2. Viral hepatitis surveillance United States, 2019
        National Center for HIV V.
        . 2021 ;2022(July 24).
        Hepatitis is an inflammation of the liver most often caused by a virus. In the US, the most common types of viral hepatitis are hepatitis A, B, and C. While each can produce similar symptoms, each hepatitis virus affects the liver differently, has different routes of transmission and infection, and typically affects different populations. Fortunately, effective vaccines are available to help prevent hepatitis A and hepatitis B. Although no vaccine is available for hepatitis C, life-saving treatment can cure the virus. Learn more about the different viral hepatitis types.

      3. Treating Medicaid patients with hepatitis C: clinical and economic impact
        Younossi Z, Gordon SC, Ahmed A, Dieterich D, Saab S, Beckerman R.
        Am J Manag Care. 2017 Feb;23(2):107-112.
        OBJECTIVES: To estimate change in chronic hepatitis C virus (HCV) disease and the economic burden associated with comprehensive treatment of the chronic HCV-infected Medicaid population. STUDY DESIGN: Decision-analytic Markov model. METHODS: Treatment-naïve patients with genotype 1 chronic HCV were followed over a lifetime horizon from the third-party payer perspective. Patients entered the model insured under Medicaid and were treated under state-specific restrictions by Metavir fibrosis stage (base case) or all treated (all-patient strategy) with an approved all-oral regimen (ledipasvir/sofosbuvir [LDV/SOF] for 8 weeks or 12 weeks, depending on cirrhosis status, viral load, and state-specific LDV/SOF restrictions). Untreated patients were assumed to age into Medicare at 65 years, where they were treated with LDV/SOF without restriction by fibrotic stage. RESULTS: The sustained virologic response (SVR) rate of the current Medicaid LDV/SOF restriction strategy was 75.2% versus 95.9% if all LDV/SOF-eligible patients were treated under Medicaid. Treating all eligible Medicaid patients with LDV/SOF, regardless of fibrotic stage, was projected to result in 36,752 fewer cases of cirrhosis; 1739 fewer liver transplants; 8169 fewer cases of hepatocellular carcinoma; 16,173 fewer HCV-related deaths; 0.84 additional life-years per patient; and 1.03 additional quality-adjusted life-years per patient. Treating all Medicaid patients with chronic HCV using LDV/SOF resulted in a 39.4% ($3.8 billion) savings and decreased the proportion of total costs attributable to downstream costs of care to 18.3%. CONCLUSIONS: A "treat all" strategy in a Medicaid population resulted in superior SVRs, substantial reductions in downstream negative clinical outcomes, and considerable cost savings. Current restrictive state policies regarding HCV treatment in Medicaid populations must be reassessed in light of these data.

      4. Direct-Acting Antiviral Agents for Patients With Hepatitis C Virus Genotype 1 Infection Are Cost-Saving
        Chhatwal J, He T, Hur C, Lopez-Olivo M.
        Clin Gastroenterol Hepatol. 2017 2017/06/01/;15(6):827-837.e8.
        Background & Aims Direct-acting antivirals (DAAs) are effective in treatment of hepatitis C virus (HCV) genotype 1 infection, but their cost and value have been debated. We performed a systematic review of published cost-effectiveness analyses of DAAs, synthesized their results with updated drug prices, and calculated the maximum price at which DAA therapy for HCV genotype 1 infection is cost-effective (increased quality-adjusted life-years [QALYs] and increased cost that the society is willing to pay) and cost-saving (increased QALYs and decreased costs). Methods We conducted a systematic review of the PubMed, Medline, EMBASE, Cochrane library, EconLit, Database of Abstracts of Reviews of Effects, National Health Service Economic Evaluation Database, Health Technology Assessment, and Tufts University databases for cost-effectiveness analyses published from 2011 through 2015. Our analysis included cost effectiveness of DAAs versus previous standard-of-care regimens (peginterferon and ribavirin, boceprevir and telaprevir), or no treatment, performed for patients with HCV genotype 1 infection. We excluded studies that were not written in English or those that did not report QALYs. Reported incremental cost-effectiveness ratios (ICERs) and treatment costs for each comparison were extracted; the threshold price was estimated for each analysis in which regimens were found to be cost-effective (ICER ≤$100,000/QALY) or cost-saving (ICER <$0), those that decreased costs and increased QALYs. Results We identified 24 cost-effectiveness studies that reported 170 ICERs for combinations of 11 drugs, from 11 countries. Of those, 81 ICERs were determined for first-generation DAAs (boceprevir and telaprevir) and 89 ICERs were determined for second-generation DAAs (drugs approved after the first-generation DAAs) as a primary intervention. The median threshold prices at which first-generation and second-generation DAAs became cost-effective were estimated as $120,100 (interquartile range, $90,700–$176,800) and $227,200 (interquartile range, $142,800–$355,800), respectively. At the discounted price of $60,000, a total of 71% of the analyses found second-generation DAAs to be cost-saving and 22% to be cost-effective. Conclusions In a systematic review, we found treatment of HCV genotype 1 infection with second-generation DAAs to be cost-effective when they cost less than and $227,200; these drugs produced cost savings at current discounts.

      5. Using national pharmacy claims data for 2014–2020, 843 329 persons were treated for hepatitis C at least once. The proportion treated increased annually among persons aged &lt;40 years, insured by Medicaid, and treated by primary care providers. Monitoring hepatitis C treatment is essential to identify barriers to treatment access.

      6. Late presenters among minority patients with chronic hepatitis C infection in the USA
        Pan C, Rabinovich C, Gayam V, Normatov M, Fidman B, Wang D.
        Int J Public Health. 2020 2020/09/01;65(7):1181-1191.
        Minority patients are under-screened for chronic hepatitis C (CHC) in the USA, and limited data exist for minority patients with advanced fibrosis.

      7. Removal of medicaid restrictions were associated with increased hepatitis C virus treatment rates, but disparities persist
        Nephew L, Wang Y, Mohamed K, Nichols D, Rawl S, Orman E, Desai A, Patidar K, Ghabril M, Chalasani N, Kasting M.
        J Viral Hepat. 2022 ;29(5):366-374.
        Abstract Despite the release of a growing number of direct-acting antivirals and evolving policy landscape, many of those diagnosed with hepatitis C virus (HCV) have not received treatment. Those from vulnerable populations are at particular risk of being unable to access treatment, threatening World Health Organization (WHO) HCV elimination goals. The aim of this study was to understand the association between direct-acting antivirals approvals, HCV-related policy changes and access to HCV virus treatment in Indiana, and to explore access to treatment by race, birth cohort and insurance type. We performed a retrospective cohort study of adults with HCV from 05/2011-03/2021, using statewide electronic health data. Nine policy and treatment changes were defined a priori. A Lowess curve evaluated treatment trends over time. Monthly screening and treatment rates were examined. Multivariable logistic regression explored predictors of treatment. The population (N = 10,336) was 13.4% Black, 51.8% was born after 1965 and 44.7% was Medicaid recipients. Inflections in the Lowess curve defined four periods: (1) Interferon + DAA, (2) early direct-acting antivirals, (3) Medicaid expansion/optimization and (4) Medicaid restrictions (fibrosis/prescriber) removed. The largest increase in monthly treatment rates was during period 4, when Medicaid prescriber and fibrosis restrictions were removed (2.4 persons per month [PPM] in period 1 to 72.3 PPM in period 4, p < 0.001; 78.0% change in slope). Multivariable logistic regression analysis showed being born after 1965 (vs. before 1945; OR 0.69; 95% 0.49–0.98) and having Medicaid (vs. private insurance; OR 0.47; 95% CI 0.42–0.53), but not race was associated with lower odds of being treated. In conclusion, DAAs had limited impact on HCV treatment rates until Medicaid restrictions were removed. Additional policies may be needed to address HCV treatment-related age and insurance disparities.

      8. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study
        Carrat F, Fontaine H, Dorival C, Simony M, Diallo A, Hezode C, De Ledinghen V, Larrey D, Haour G, Bronowicki J, Zoulim F, Asselah T, Marcellin P, Thabut D, Leroy V, Tran A, Habersetzer F, Samuel D, Guyader D, Chazouilleres O, Mathurin P, Metivier S, Alric L, Riachi G, Gournay J, Abergel A, Cales P, Ganne N, Loustaud-Ratti V, D'Alteroche L, Causse X, Geist C, Minello A, Rosa I, Gelu-Simeon M, Portal I, Raffi F, Bourliere M, Pol S.
        The Lancet. 2019 2019/04/06/;393(10179):1453-1464.
        Summary Background Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort. Methods We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458. Findings Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0–40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07–3·71) and decompensated cirrhosis (3·83, 2·29–6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33–0·70) and hepatocellular carcinoma (0·66, 0·46–0·93), and was not associated with decompensated cirrhosis (1·14, 0·57–2·27). Interpretation Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection. Funding INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.

      9. Interventions to enhance testing, linkage to care, and treatment initiation for hepatitis C virus infection: a systematic review and meta-analysis
        Cunningham E, Wheeler A, Hajarizadeh B, French C, Roche R, Marshall A, Fontaine G, Conway A, Valencia B, Bajis S, Presseau J, Ward J, Degenhardt L, Dore G, Hickman M, Vickerman P, Grebely J.
        Lancet Gastroenterol Hepatol. 2022 2022/05/01/;7(5):426-445.
        Summary Background Despite the goal set by WHO to eliminate hepatitis C virus (HCV) as a public health threat, uptake of HCV testing and treatment remains low. To achieve this target, evidence-based interventions are needed to address the barriers to care for people with, or at risk of, HCV infection. We aimed to assess the efficacy of interventions to improve HCV antibody testing, HCV RNA testing, linkage to HCV care, and treatment initiation. Methods In this systematic review and meta-analysis, we searched MEDLINE (PubMed), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, and PsycINFO without language restrictions for reports published between database inception and July 21, 2020, assessing the following primary outcomes: HCV antibody testing; HCV RNA testing; linkage to HCV care; and direct-acting antiviral treatment initiation. We also searched key conference abstracts. We included randomised and non-randomised studies assessing non-pharmaceutical interventions that included a comparator or control group. Studies were excluded if they enrolled only paediatric populations (aged <18 years) or if they conducted the intervention in a different health-care setting to that of the control or comparator. Authors were contacted to clarify study details and to obtain additional population-level data. Data were extracted from the records identified into a pre-piloted and standardised data extraction form and a random-effects meta-analysis was used to pool the effects of the interventions on study outcomes. This study is registered in PROSPERO, CRD42020178035. Findings Of 15 342 unique records identified, 142 were included, which reported on 148 unique studies (47 randomised controlled trials and 101 non-randomised studies). Medical chart reminders, provider education, and point-of-care antibody testing significantly improved at least three study outcomes compared with a comparator or control. Interventions that simplified HCV testing, including dried blood spot testing, point-of-care antibody testing, reflex RNA testing, and opt-out screening, significantly improved testing outcomes compared with a comparator or control. Enhanced patient and provider support through patient education, provider care coordination, and provider education also significantly improved testing outcomes compared with a comparator or control. Integrated care and patient navigation or care coordination significantly improved linkage to care and the uptake of direct-acting antiviral treatment compared with a comparator or control. Interpretation Several interventions to improve HCV care that address several key barriers to HCV care were identified. New models of HCV care must be designed and implemented to address the barriers faced by the population of interest. Further high-quality research, including rigorously designed randomised studies, is still needed in key populations. Funding None.

      10. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial
        Solomon S, Wagner-Cardoso S, Smeaton L, Sowah L, Wimbish C, Robbins G, Brates I, Scello C, Son A, Avihingsanon A, Linas B, Anthony D, Nunes E, Kliemann D, Supparatpinyo K, Kityo C, Tebas P, Bennet J, Santana-Bagur J, Benson C, Van Schalkwyk M, Cheinquer N, Naggie S, Wyles D, Sulkowski M.
        Lancet Gastroenterol Hepatol. 2022 2022/04/01/;7(4):307-317.
        Summary Background Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. Methods ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (−2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. Findings Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4–96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. Interpretation In this diverse global population of people with HCV, the MINMON approach with sofosbuvir–velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. Funding

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Evaluating natural experiments that impact the diabetes epidemic: An introduction to the NEXT-D3 Network
        Siegel KR, Ali MK, Ackermann RT, Black B, Huguet N, Kho A, Mangione CM, Nauman E, Ross-Degnan D, Schillinger D, Shi L, Wharam JF, Duru OK.
        Curr Diab Rep. 2022 Aug;22(8):393-403.
        PURPOSE OF REVIEW: Diabetes is an ongoing public health issue in the USA, and, despite progress, recent reports suggest acute and chronic diabetes complications are increasing. RECENT FINDINGS: The Natural Experiments for Translation in Diabetes 3.0 (NEXT-D3) Network is a 5-year research collaboration involving six academic centers (Harvard University, Northwestern University, Oregon Health & Science University, Tulane University, University of California Los Angeles, and University of California San Francisco) and two funding agencies (Centers for Disease Control and Prevention and National Institutes of Health) to address the gaps leading to persisting diabetes burdens. The network builds on previously funded networks, expanding to include type 2 diabetes (T2D) prevention and an emphasis on health equity. NEXT-D3 researchers use rigorous natural experiment study designs to evaluate impacts of naturally occurring programs and policies, with a focus on diabetes-related outcomes. NEXT-D3 projects address whether and to what extent federal or state legislative policies and health plan innovations affect T2D risk and diabetes treatment and outcomes in the USA; real-world effects of increased access to health insurance under the Affordable Care Act; and the effectiveness of interventions that reduce barriers to medication access (e.g., decreased or eliminated cost sharing for cardiometabolic medications and new medications such as SGLT-2 inhibitors for Medicaid patients). Overarching goals include (1) expanding generalizable knowledge about policies and programs to manage or prevent T2D and educate decision-makers and organizations and (2) generating evidence to guide the development of health equity goals to reduce disparities in T2D-related risk factors, treatment, and complications.

      2. Urinary nitrate and sodium in a high-risk area for upper gastrointestinal cancers: Golestan Cohort Study
        Etemadi A, Buller ID, Hashemian M, Roshandel G, Poustchi H, Espinosa MM, Blount BC, Pfeiffer CM, Keshavarzi B, Flory AR, Nasseri-Moghaddam S, Dawsey SM, Freedman ND, Abnet CC, Malekzadeh R, Ward MH.
        Environ Res. 2022 Jul 18:113906.
        BACKGROUND: The epidemiological evidence regarding the carcinogenicity of nitrate and sodium in drinking water is limited, partly because measuring the exposure at the individual level is complex. Most studies have used nitrate in water supplies as a proxy for individual exposure, but dietary intakes and other factors may contribute to the exposure. The present study investigates the factors associated with urinary nitrate and sodium in a high-risk area for esophageal and gastric cancers. METHODS: For this cross-sectional study, we used data and samples collected in 2004-2008 during the enrollment phase of the Golestan Cohort Study from a random sample of 349 participants (300 individuals from 24 rural villages and 49 from the city of Gonbad), stratified by average water nitrate in their district, the source of drinking water, and the usual dietary intake of nitrate and sodium. Nitrate, sodium, and creatinine were measured in a spot urine sample collected at the time of interview. We used the provincial cancer registry data to calculate the cumulative incidence rates of esophageal and gastric cancers for each location through June 1, 2020, and used weighted partial Pearson correlation to compare the incidence rates with median urinary nitrate and sodium in each village or the city. RESULTS: Among 349 participants (mean age±SD: 50.7 ± 8.6 years), about half (n = 170) used groundwater for drinking, and the use of ground water was significantly more common in high-elevation locations (75.8%). The geometric mean of the creatinine-corrected urinary nitrate concentration was 68.3 mg/g cr (95%CI: 64.6,72.3), and the corresponding geometric mean for urinary sodium was 150.0 mmoL/g cr (95%CI: 139.6161.1). After adjusting for confounders, urinary nitrate was associated with being a woman, drinking groundwater, and living in high-elevation locations, but not with estimated dietary intake. Urinary sodium concentration was significantly associated with monthly precipitation at the time of sampling but not with elevation or drinking water source. There were significant positive correlations between both median urinary nitrate and sodium in each location and esophageal cancer incidence rates adjusted for sex and age (r = 0.65 and r = 0.58, respectively, p < 0.01), but not with gastric cancer incidence. CONCLUSION: In a rural population at high risk for esophageal and gastric cancers, nitrate excretion was associated with living at a higher elevation and using groundwater for drinking. The associations between nitrate and sodium excretion with esophageal cancer incidence warrant future investigation.

      3. Cardiovascular disease risk factors in US adults with vision impairment
        Mendez I, Kim M, Lundeen EA, Loustalot F, Fang J, Saaddine J.
        Prev Chronic Dis. 2022 Jul 21;19:E43.
        INTRODUCTION: Adults with vision impairment (VI) have a higher prevalence of cardiovascular disease (CVD) compared with those without VI. We estimated the prevalence of CVD and CVD risk factors by VI status in US adults. METHODS: We used nationally representative data from the 2018 National Health Interview Survey (N = 22,890 adults aged ≥18 years). We estimated the prevalence of self-reported diagnosis of CVD (coronary heart disease [including angina and myocardial infarction], stroke, or other heart disease) by VI status. We used separate logistic regression models to generate adjusted prevalence ratios (aPRs), controlling for sociodemographic covariates, for those with VI (reference group, no VI) for CVD and CVD risk factors: current smoking, physical inactivity, excessive alcohol intake, obesity, hypertension, high cholesterol, and diabetes. RESULTS: Overall, 12.9% (95% CI, 12.3-13.5) of the sample had VI. The prevalence of CVD was 26.6% (95% CI, 24.7-28.6) in people with VI versus 12.2% (95% CI, 11.7-12.8) in those without VI (aPR = 1.65 [95% CI, 1.51-1.80]). Compared with adults without VI, those with VI had a higher prevalence of all risk factors examined: current smoking (aPR = 1.40 [95% CI, 1.27-1.53]), physical inactivity (aPR = 1.14 [95% CI, 1.06-1.22]), excessive alcohol intake (aPR = 1.29 [95% CI, 1.08-1.53]), obesity (aPR = 1.28 [95% CI, 1.21-1.36]), hypertension (aPR = 1.29 [95% CI, 1.22-1.36]), high cholesterol (aPR = 1.21 [95% CI, 1.14-1.29]), and diabetes (aPR = 1.54 [95% CI, 1.38-1.72]). CONCLUSION: Adults with VI had a higher prevalence of CVD and CVD risk factors compared with those without VI. Effective clinical and lifestyle interventions, adapted to accommodate VI-related challenges, may help reduce CVD risk in adults with VI.

      4. Multi-component interventions and change in screening rates in primary care clinics in the Colorectal Cancer Control Program
        Sharma KP, DeGroff A, Hohl SD, Maxwell AE, Escoffery NC, Sabatino SA, Joseph DA.
        Prev Med Rep. 2022 Oct;29:101904.
        Colorectal cancer (CRC) screening has been shown to decrease CRC mortality. Implementation of evidence-based interventions (EBIs) increases CRC screening. The purpose of this analysis is to determine which combinations of EBIs or strategies led to increases in clinic-level screening rates among clinics participating in CDC's Colorectal Cancer Control Program (CRCCP). Data were collected from CRCCP clinics between 2015 and 2018 and the analysis was conducted in 2020. The outcome variable was the annual change in clinic level CRC screening rate in percentage points. We used first difference (FD) estimator of linear panel data regression model to estimate the associations of outcome with independent variables, which include different combinations of EBIs and intervention strategies. The study sample included 486 unique clinics with 1156 clinic years of total observations. The average baseline screening rate was 41 % with average annual increase of 4.6 percentage points. Only two out of six combinations of any two EBIs were associated with increases in screening rate (largest was 6.5 percentage points, P < 0.001). Any combinations involving three EBIs or all four EBIs were significantly associated with the outcome with largest increase of 7.2 percentage points (P < 0.001). All interventions involving 2-3 strategies led to increases in rate with largest increase associated with the combination of increasing community demand and access (6.1 percentage points, P < 0.001). Clinics implementing combinations of these EBIs, particularly those including three or more EBIs, often were more likely to have impact on screening rate change than those implementing none.

      5. PURPOSE: To evaluate the psychometric properties of the patient-reported outcome measurement information system® (PROMIS) short forms for assessing sleep disturbance, sleep-related impairment, pain interference, and pain behavior, among adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHODS: Data came from the Multi-Site ME/CFS study conducted between 2012 and 2020 at seven ME/CFS specialty clinics across the USA. Baseline and follow-up data from ME/CFS and healthy control (HC) groups were used to examine ceiling/floor effects, internal consistency reliability, differential item functioning (DIF), known-groups validity, and responsiveness. RESULTS: A total of 945 participants completed the baseline assessment (602 ME/CFS and 338 HC) and 441 ME/CFS also completed the follow-up. The baseline mean T-scores of PROMIS sleep and pain measures ranged from 57.68 to 62.40, about one standard deviation above the national norm (T-score = 50). All four measures showed high internal consistency (ω = 0.92 to 0.97) and no substantial floor/ceiling effects. No DIF was detected by age or sex. Known-groups comparisons among ME/CFS groups with low, medium, and high functional impairment showed significant small-sized differences in scores (η(2) = 0.01 to 0.05) for the two sleep measures and small-to-medium-sized differences (η(2) = 0.01 to 0.15) for the two pain measures. ME/CFS participants had significantly worse scores than HC (η(2) = 0.35 to 0.45) for all four measures. Given the non-interventional nature of the study, responsiveness was evaluated as sensitivity to change over time and the pain interference measure showed an acceptable sensitivity. CONCLUSION: The PROMIS sleep and pain measures demonstrated satisfactory psychometric properties supporting their use in ME/CFS research and clinical practice.

      6. Racial differences in venous thromboembolism: A surveillance program in Durham County, North Carolina
        Saber I, Adamski A, Kuchibhatla M, Abe K, Beckman M, Reyes N, Schulteis R, Pendurthi Singh B, Sitlinger A, Thames EH, Ortel TL.
        Res Pract Thromb Haemost. 2022 Jul;6(5):e12769.
        BACKGROUND: Venous thromboembolism (VTE) affects approximately 1-2 individuals per 1000 annually and is associated with an increased risk for pulmonary hypertension, postthrombotic syndrome, and recurrent VTE. OBJECTIVE: To determine risk factors, incidence, treatments, and outcomes of VTE through a 2-year surveillance program initiated in Durham County, North Carolina (population approximately 280,000 at time of study). PATIENTS/METHODS: We performed a retrospective analysis of data actively collected from three hospitals in Durham County during the surveillance period. RESULTS: A total of 987 patients were diagnosed with VTE, for an annual rate of 1.76 per 1000 individuals. Hospital-associated VTE occurred in 167 hospitalized patients (16.9%) and 271 outpatients who were hospitalized within 90 days of diagnosis (27.5%). Annual incidence was 1.98 per 1000 Black individuals compared to 1.25 per 1000 White individuals (p < 0.0001), and Black individuals with VTE were younger than White individuals (p < 0.0001). Common risk factors included active cancer, prolonged immobility, and obesity, and approximately half were still taking anticoagulant therapy 1 year later. A total of 224 patients died by 1 year (28.5% of patients for whom outcomes could be confirmed), and Black patients were more likely to have recurrent VTE than White patients during the first 6 months following initial presentation (9.4% vs. 4.1%, p = 0.01). CONCLUSIONS: Ongoing surveillance provides an effective strategy to identify patients with VTE and monitor treatment and outcomes. We demonstrated that hospital-associated VTE continues to be a major contributor to the burden of VTE and confirmed the higher incidence of VTE in Black compared to White individuals.

    • Communicable Diseases
      1. Longitudinal HIV care outcomes by gender identity in the United States
        Lesko CR, Edwards JK, Hanna DB, Mayor AM, Silverberg MJ, Horberg M, Rebeiro PF, Moore RD, Rich AJ, McGinnis KA, Buchacz K, Crane HM, Rabkin CS, Althoff KN, Poteat TC.
        AIDS. 2022 Jul 21.
        OBJECTIVE: Describe engagement in HIV care over time after initial engagement in HIV care, by gender identity. DESIGN: Observational, clinical cohort study of people with HIV engaged in routine HIV care across the United States. METHODS: We followed people with HIV who linked to and engaged in clinical care (attending ≥2 visits in 12 months) in cohorts in the North American Transgender Cohort Collaboration, 2000-2018. Within strata of gender identity, we estimated the 7-year (84-month) restricted mean time spent: lost-to-clinic (stratified by pre-/post-antiretroviral therapy (ART) initiation); in care prior to ART initiation; on ART but not virally suppressed; virally suppressed (≤200 copies/mL); or dead (pre-/post-ART initiation). RESULTS: Transgender women (N = 482/101,841) spent an average of 35.5 out of 84 months virally suppressed (this was 30.5 months for cisgender women and 34.4 months for cisgender men). After adjustment for age, race, ethnicity, history of injection drug use, cohort, and calendar year, transgender women were significantly less likely to die than cisgender people. Cisgender women spent more time in care not yet on ART, and less time on ART and virally suppressed, but were less likely to die compared with cisgender men. Other differences were not clinically meaningful. CONCLUSIONS: In this sample, transgender women and cisgender people spent similar amounts of time in care and virally suppressed. Additional efforts to improve retention in care and viral suppression are needed for all people with HIV, regardless of gender identity.

      2. Clinical outcomes in a randomized controlled trial comparing point-of-care versus standard HIV viral load monitoring in Nigeria
        Chang C, Agbaji O, Mitruka K, Olatunde B, Sule H, Dajel T, Zee A, Ahmed ML, Ahmed I, Okonkwo P, Chaplin B, Kanki P.
        Clin Infect Dis. 2022 Jul 22.
        BACKGROUND: Point-of-care (POC) viral load (VL) tests provide results within hours, enabling same-day treatment interventions. We assessed treatment outcomes with POC versus standard-of-care (SOC) VL monitoring. METHODS: We implemented a randomized controlled trial at an urban and rural hospital in Nigeria. Participants initiating antiretroviral therapy (ART) were randomized 1:1 for monitoring via the POC Cepheid Xpert® or SOC Roche COBAS® (v2.0) HIV-1 VL assays. Viral suppression (VS) and retention in care at 12 months were compared via intention-to-treat (ITT) and per-protocol (PP) analyses. Post-trial surveys for POC patients and health care workers (HCWs) evaluated acceptability. RESULTS: During April 2018 -October 2019, 268 SOC and 273 POC patients enrolled in the trial. VS at <1000 copies/mL at 12 months was 59.3% (162/273) for POC and 52.2% (140/268) for SOC (p = 0.096) in ITT analysis, and 77.1% (158/205) for POC and 65.9% (137/208) for SOC (p = 0.012) in PP analysis. Retention was not significantly different in ITT analysis but was 85.9% for POC and 76.9% for SOC (p = 0.02) in PP analysis. The increased VS in the POC arm was attributable to improved retention and documentation of VL results. POC monitoring was preferred over SOC by 90.2% (147/163) of patients and 100% (15/15) of HCW thought it facilitated patient care. CONCLUSIONS: POC VL monitoring did not improve 12-month VS among those with results but did improve retention and VS documentation and was preferred by most patients and HCWs. Further research can inform best POC implementation conditions and approaches to optimize patient care.

      3. The timeliness of point of care viral load results improves HIV monitoring in Nigeria
        Chaplin B, Agbaji O, Nieva HR, Olatunde B, Chang C, Mitruka K, Sule H, Dajel T, Zee A, Ahmed ML, Ahmed I, Okonkwo P, Rawizza H, Kanki P.
        Clin Infect Dis. 2022 Jul 24.
        BACKGROUND: HIV viral load (VL) monitoring is critical for antiretroviral therapy (ART) management. Point-of-care (POC) VL testing has been reported to be feasible and preferred over standard of care (SOC) testing in many low- and middle-income country (LMIC) settings, where rapid results could improve patient outcomes. METHODS: The timeliness of receipt of VL results was evaluated as part of an open label randomized controlled trial among patients newly initiating ART assessing clinical outcomes with POC VL monitoring using Cepheid Xpert® versus SOC VL at Jos University Teaching Hospital (JUTH) and Comprehensive Health Centre Zamko (CHCZ), in Nigeria. We determined the median number of days between specimen collection and recording of VL results in patient charts, patient receipt of results, and ART switch for those meeting virologic failure criteria. RESULTS: Between April 2018 and October 2019, we screened 696 ART-naïve individuals; 273 were randomized to POC and 268 to SOC HIV-1 VL testing. Participants in the POC arm received VL results significantly faster than those in the SOC arm (0.1 median days [IQR:0.1-0.2] versus 143.1 median days [IQR:56.0-177.1], respectively; p < 0.0001). Participants in the POC arm with confirmed virologic failure versus those in the SOC arm were switched more rapidly to a second-line regimen (0 median days [IQR:0-28] versus 66 days [IQR:63-123], respectively; p = 0.03). CONCLUSIONS: POC VL testing resulted in significant improvement in the timeliness of VL result receipt by patients and use for effective HIV clinical management. In patients experiencing VL failure, POC monitoring enabled prompt switching to second-line ART regimens.

      4. Simultaneous late, late-onset group B streptococcal meningitis in identical twins
        Sherman G, Lamb GS, Platt CD, Wessels MR, Chochua S, Nakamura MM.
        Clin Pediatr (Phila). 2022 Jul 26:99228221113630.
        To our knowledge, late, late-onset group B streptococcal (GBS) meningitis in identical twins has yet to be reported. We describe a case of 14-week-old twins who developed fever hours apart and presented simultaneously to the emergency department 2 days later with seizures. Blood and cerebrospinal fluid (CSF) cultures from both infants were positive for GBS. Their clinical courses were highly similar, with magnetic resonance imaging (MRI) demonstrating ventriculitis and subdural empyema, complicated by clinical and subclinical seizures requiring quadruple antiepileptic treatment. The CSF was sterile for both on follow-up lumbar puncture 48 hours after the initial positive CSF culture. Both showed marked improvement on antimicrobial and antiepileptic therapy, with fever resolving after 5 days of therapy, control of seizures, and slowly improving MRI findings. Twin A received a 6-week course of penicillin, whereas twin B received 6 weeks plus an additional 10 days due to persistent left cochlear enhancement consistent with labyrinthitis. Evaluation for an underlying primary immunodeficiency was negative. Genomic analysis revealed that the patients' CSF GBS isolates were essentially identical and of capsular polysaccharide serotype Ia.

      5. Participation in an HIV prevention intervention and access to and use of contraceptives among young women: a cross sectional analysis in six South African districts
        Jonas K, Lombard C, Chirinda W, Govindasamy D, Appollis TM, Kuo C, Gray G, Beauclair R, Cheyip M, Mathews C.
        Contraception. 2022 Jul 23.
        OBJECTIVE: This study investigated whether young women's participation in a combination HIV-prevention intervention was associated with accessing and using condoms and other contraceptives. STUDY DESIGN: A cross-sectional household survey was conducted from 2017 - 2018 among a representative sample of young women aged 15 - 24 years old living in six South African districts in which the intervention was implemented. Cross-tabulations and multivariate regression analyses of weighted data were performed to examine access to and use of condoms and other contraceptives. RESULTS: In total 4399 young women participated, representing a 60.6% response rate. Of participants, 61.0% (n=2685) reported accessing condoms and other contraceptives in the past year. Among those who ever had sex (n=3009), 51.0% used condoms and 37.4% other contraceptives at last sex. Among 15-19 year old, participation in the combination intervention was positively associated with reporting contraceptive use other than condoms at last sex (Prevalence Ratio (PR): 1.36; 95% CI: 1.21 - 1.53) and reporting use of both condoms and other contraceptives at last sex (PR: 1.45; 95% CI: 1.26 - 1.68). No associations were observed in the age group 20-24. CONCLUSION: Our findings suggest that combination HIV prevention interventions may lead to increased access and use of condoms and other methods of contraception among adolescent women, but this needs to be confirmed in experimental studies. We need to test different or more intensive interventions to increase contraceptive use in young women aged 20-24.

      6. “Testing Can Be Done Anywhere”: A qualitative assessment of targeted community-based point-of-care early infant diagnosis of HIV in Lusaka, Zambia
        Tembo T, Dale H, Muttau N, Itoh M, Williamson D, Mwamba C, Manasyan A, Beard RS, Cox MH, Herce ME.
        Glob Health Sci Pract. 2022 ;10(3).
        Introduction: Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.e., “community POC model”) to reach high-risk mother-infant pairs (MIPs) in Lusaka, Zambia. Methods: We conducted in-depth interviews with a purposive sample of health care workers, study staff, and caregivers in high-risk MIPs at 6 health facilities included in a larger implementation research study evaluating the community POC model. We defined “high-risk MIPs” as mothers who did not receive antenatal testing or an attended delivery or infants who missed EID testing milestones. Interviews were audio-recorded, translated, and transcribed verbatim in English. Content and thematic analysis were done using NVivo 10 software. Results: Health care workers (n=20) and study staff (n=12) who implemented the community POC model noted that the portability and on-screen prompts of the POC platform made it mobile and easy to use, but maintenance and supply chain management were key to field operations. Respondents also felt that the community POC model reached more infants who had never had EID testing, allowing them to find infants with HIV infection and immediately initiate them on ART. Caregivers (n=22) found the community POC model acceptable, provided that privacy could be ensured because the service was convenient and delivered close to home. Conclusion: We demonstrate the acceptability, appropriateness, and feasibility of implementing the community POC model in Zambia, while identifying potential challenges related to client privacy and platform field operations. The community POC model may represent a promising strategy to further facilitate active HIV case finding and linkage to ART for children with undiagnosed HIV infection in the community. © Tembo et al.

      7. The role of the VP4 attachment protein in rotavirus host range restriction in an in vivo suckling mouse model
        Sánchez-Tacuba L, Kawagishi T, Feng N, Jiang B, Ding S, Greenberg HB.
        J Virol. 2022 Jul 12:e0055022.
        The basis for rotavirus (RV) host range restriction (HRR) is not fully understood but is likely multigenic. RV genes encoding VP3, VP4, NSP1, NSP2, NSP3, and NSP4 have been associated with HRR in various studies. With the exception of NSP1, little is known about the relative contribution of the other RV genes to HRR. VP4 has been linked to HRR because it functions as the RV cell attachment protein, but its actual role in HRR has not been fully assessed. We generated a collection of recombinant RVs (rRVs) in an isogenic murine-like RV genetic background, harboring either heterologous or homologous VP4 genes from simian, bovine, porcine, human, and murine RV strains, and characterized these rRVs in vitro and in vivo. We found that a murine-like rRV encoding a simian VP4 was shed, spread to uninoculated littermates, and induced diarrhea comparably to rRV harboring a murine VP4. However, rRVs carrying VP4s from both bovine and porcine RVs had reduced diarrhea, but no change in fecal shedding was observed. Both diarrhea and shedding were reduced when VP4 originated from a human RV strain. rRVs harboring VP4s from human or bovine RVs did not transmit to uninoculated littermates. We also generated two rRVs harboring reciprocal chimeric murine or bovine VP4. Both chimeras replicated and caused disease as efficiently as the parental strain with a fully murine VP4. These data suggest that the genetic origin of VP4 partially modulates HRR in the suckling mouse and that both the VP8* and VP5* domains independently contribute to pathogenesis and transmission. IMPORTANCE Human group A rotaviruses (RVs) remain the most important cause of severe acute gastroenteritis among infants and young children worldwide despite the introduction of several safe and effective live attenuated vaccines. The lack of knowledge regarding fundamental aspects of RV biology, such as the genetic basis of host range restriction (HRR), has made it difficult to predictively and efficiently design improved, next-generation live attenuated rotavirus vaccines. Here, we engineered a collection of VP4 monoreassortant RVs to systematically explore the role of VP4 in replication, pathogenicity, and spread, as measures of HRR, in a suckling mouse model. The genetic and mechanistic bases of HRR have substantial clinical relevance given that this restriction forms the basis of attenuation for several replication-competent human RV vaccines. In addition, a better understanding of RV pathogenesis and the determinants of RV spread is likely to enhance our ability to improve antiviral drug and therapy development.

      8. Post-COVID-19 conditions among children 90 days after SARS-CoV-2 infection
        Funk AL, Kuppermann N, Florin TA, Tancredi DJ, Xie J, Kim K, Finkelstein Y, Neuman MI, Salvadori MI, Yock-Corrales A, Breslin KA, Ambroggio L, Chaudhari PP, Bergmann KR, Gardiner MA, Nebhrajani JR, Campos C, Ahmad FA, Sartori LF, Navanandan N, Kannikeswaran N, Caperell K, Morris CR, Mintegi S, Gangoiti I, Sabhaney VJ, Plint AC, Klassen TP, Avva UR, Shah NP, Dixon AC, Lunoe MM, Becker SM, Rogers AJ, Pavlicich V, Dalziel SR, Payne DC, Malley R, Borland ML, Morrison AK, Bhatt M, Rino PB, Beneyto Ferre I, Eckerle M, Kam AJ, Chong SL, Palumbo L, Kwok MY, Cherry JC, Poonai N, Wassem M, Simon NJ, Freedman SB.
        JAMA Netw Open. 2022 Jul 1;5(7):e2223253.
        IMPORTANCE: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE: SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

      9. Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines
        Wang L, Kainulainen MH, Jiang N, Di H, Bonenfant G, Mills L, Currier M, Shrivastava-Ranjan P, Calderon BM, Sheth M, Mann BR, Hossain J, Lin X, Lester S, Pusch EA, Jones J, Cui D, Chatterjee P, Jenks MH, Morantz EK, Larson GP, Hatta M, Harcourt JL, Tamin A, Li Y, Tao Y, Zhao K, Lacek K, Burroughs A, Wang W, Wilson M, Wong T, Park SH, Tong S, Barnes JR, Tenforde MW, Self WH, Shapiro NI, Exline MC, Files DC, Gibbs KW, Hager DN, Patel M, Halpin AL, McMullan LK, Lee JS, Xia H, Xie X, Shi PY, Davis CT, Spiropoulou CF, Thornburg NJ, Oberste MS, Dugan VG, Wentworth DE, Zhou B.
        Nat Commun. 2022 Jul 27;13(1):4350.
        The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.

      10. U.S. Black women and human immunodeficiency virus preexposure prophylaxis implementation
        Hoover KW, Kourtis AP, Smith DK.
        Obstet Gynecol. 2022 Jul 1;140(1):106-109.
        Black women are disproportionately affected by the U.S. human immunodeficiency virus (HIV) epidemic. Preexposure prophylaxis (PrEP) is a safe and effective intervention for HIV prevention. Increased PrEP implementation is a pillar of the U.S. Department of Health and Human Services' Ending the HIV Epidemic in the U.S. initiative. However, PrEP has been used by a smaller proportion of women with PrEP indications compared with men. The goals of the Ending the HIV Epidemic in the U.S. initiative can be achieved only by increasing PrEP use among Black women. Obstetricians and gynecologists are uniquely poised to provide PrEP services for women. We describe the need for community-to-clinic models to overcome the barriers to PrEP use by Black women and a roadmap for clinician and community organization collaboration to increase access to and use of PrEP by Black women.

      11. Examination of common coronavirus antibodies in SARS-CoV-2-infected and uninfected participants in a household transmission investigation
        Stumpf MM, Freeman B, Mills L, Lester S, Chu VT, Kirking HL, Thornburg NJ, Killerby ME.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac212.
        We compared paired serum specimens from household contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases with detectable SARS-CoV-2 seroconversion with contacts who remained seronegative. No protection from SARS-CoV-2 infection was associated with human coronavirus antibodies; however, an increase in common betacoronavirus antibodies was associated with seroconversion to SARS-CoV-2 in mild to moderately ill cases.

      12. Receipt of baseline laboratory testing recommended by the HIV medicine association for people initiating HIV care, United States, 2015-2019
        Weiser J, Tie Y, Lu JF, Colasanti JA, Fanfair RN, Beer L.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac280.
        BACKGROUND: The HIV Medicine Association of the Infectious Disease Society of America publishes Primary Care Guidance for Persons with Human Immunodeficiency Virus. We assessed receipt of recommended baseline tests among newly diagnosed patients initiating HIV care. METHODS: The Medical Monitoring Project is a Centers for Disease Control and Prevention survey designed to produce nationally representative estimates of behavioral and clinical characteristics of adults with diagnosed HIV in the United States. We analyzed data for 725 participants in the 2015-2019 data collection cycles who received an HIV diagnosis within the past 2 years and had ≥1 HIV provider visit. We estimated the prevalence of having recommended tests after the first HIV provider visit and between 3 months before and 3/6 months after the first HIV provider visit and estimated prevalence differences of having 4 combinations of tests by sociodemographic and clinical characteristics. RESULTS: Within 6 months of care initiation, HIV monitoring tests were performed for 91.3% (95% CI, 88.7%-93.8%) of patients; coinfection blood tests, 27.5% (95% CI, 22.5%-32.4%); site-based STI tests, 59.7% (95% CI, 55.4%-63.9%); and blood chemistry and hematology tests, 50.8% (95% CI, 45.8%-55.8%). Patients who were younger, gay, or bisexual were more likely to receive site-based STI tests, and patients receiving care at Ryan White HIV/AIDS Program (RWHAP)-funded facilities were more likely than patients at non-RWHAP-funded facilities to receive all test combinations. CONCLUSIONS: Receipt of recommended baseline tests among patients initiating HIV care was suboptimal but was more likely among patients at RWHAP-funded facilities. Embedding clinical decision support in HIV provider workflow could increase recommended baseline testing.

      13. Children, adolescents, and young adults hospitalized with COVID-19 and diabetes in summer 2021
        Agathis NT, Womack LS, Webber BJ, Choudhary R, Wanga V, Ko JY, Dupont H, Imperatore G, Koumans EH, Saydah S, Kimball AA, Siegel DA.
        Pediatr Diabetes. 2022 Jul 25.
        INTRODUCTION: More information is needed to understand the clinical epidemiology of youth hospitalized with diabetes and COVID-19. We describe the demographic and clinical characteristics of patients <21 years old hospitalized with COVID-19 and either Type 1 or Type 2 Diabetes Mellitus (T1DM or T2DM) during peak incidence of SARS-CoV-2 infection with the B.1.617.2 (Delta) variant. METHODS: This is a descriptive sub-analysis of a retrospective chart review of patients aged <21 years hospitalized with COVID-19 in six US children's hospitals during July-August 2021. Patients with COVID-19 and either newly diagnosed or known T1DM or T2DM were described using originally collected data and diabetes-related data specifically collected on these patients. RESULTS: Of the 58 patients hospitalized with COVID-19 and diabetes, 34 had T1DM and 24 had T2DM. Of those with T1DM and T2DM, 26% (9/34) and 33% (8/24), respectively, were newly diagnosed. Among those >12 years old and eligible for COVID-19 vaccination, 93% were unvaccinated (42/45). Among patients with T1DM, 88% had diabetic ketoacidosis (DKA) and 6% had COVID-19 pneumonia; of those with T2DM, 46% had DKA and 58% had COVID-19 pneumonia. Of those with T1DM or T2DM, 59% and 46%, respectively, required ICU admission. CONCLUSION: Our findings highlight the importance of considering diabetes in the evaluation of youth presenting with COVID-19; the challenges of managing young patients who present with both COVID-19 and diabetes, particularly T2DM; and the importance of preventive actions like COVID-19 vaccination to prevent severe illness among those eligible with both COVID-19 and diabetes. This article is protected by copyright. All rights reserved.

      14. Spatial distribution and determinants of HIV prevalence among adults in urban Ethiopia: Findings from the Ethiopia Population-based HIV Impact Assessment Survey (2017-2018)
        Gelibo T, Lulseged S, Eshetu F, Abdella S, Melaku Z, Ajiboye S, Demissie M, Solmo C, Ahmed J, Getaneh Y, Kaydos-Daniels SC, Abate E.
        PLoS One. 2022 ;17(7):e0271221.
        The design and evaluation of national HIV programs often rely on aggregated national data, which may obscure localized HIV epidemics. In Ethiopia, even though the national adult HIV prevalence has decreased, little information is available about local areas and subpopulations. To inform HIV prevention efforts for specific populations, we identified geographic locations and drivers of HIV transmission. We used data from adults aged 15-64 years who participated in the Ethiopian Population-based HIV Impact Assessment survey (October 2017-April 2018). Location-related information for the survey clusters was obtained from the 2007 Ethiopia population census. Spatial autocorrelation of HIV prevalence data were analyzed via a Global Moran's I test. Geographically weighted regression analysis was used to show the relationship of covariates. The finding indicated that uncircumcised men in certain hotspot towns and divorced or widowed individuals in hotspot woredas/towns might have contributed to the average increase in HIV prevalence in the hotspot areas. Hotspot analysis findings indicated that, localized, context-specific intervention efforts tailored to at-risk populations, such as divorced or widowed women or uncircumcised men, could decrease HIV transmission and prevalence in urban Ethiopia.

      15. An examination of SARS-CoV-2 transmission based on classroom distancing in schools with other preventive measures in place-Missouri, January-March 2021
        Donovan CV, Worrell MC, Steinberg J, Montgomery BK, Young R, Richardson G, Dawson P, Dinh TH, Botkin N, Fitzpatrick T, Fields A, Rains CM, Fritz S, Malone S, Tong S, Mooney J, Newland JG, Barrios LC, Neatherlin JC, Salzer JS.
        Public Health Rep. 2022 Jul 16:333549221109003.
        OBJECTIVES: Classroom layout plays a central role in maintaining physical distancing as part of a multicomponent prevention strategy for safe in-person learning during the COVID-19 pandemic. We conducted a school investigation to assess layouts and physical distancing in classroom settings with and without in-school SARS-CoV-2 transmission. METHODS: We assessed, measured, and mapped 90 K-12 (kindergarten through grade 12) classrooms in 3 Missouri public school districts during January-March 2021, prior to widespread prevalence of the Delta variant; distances between students, teachers, and people with COVID-19 and their contacts were analyzed. We used whole-genome sequencing to further evaluate potential transmission events. RESULTS: The investigation evaluated the classrooms of 34 students and staff members who were potentially infectious with COVID-19 in a classroom. Of 42 close contacts (15 tested) who sat within 3 ft of possibly infectious people, 1 (2%) probable transmission event occurred (from a symptomatic student with a longer exposure period [5 days]); of 122 contacts (23 tested) who sat more than 3 ft away from possibly infectious people with shorter exposure periods, no transmission events occurred. CONCLUSIONS: Reduced student physical distancing is one component of mitigation strategies that can allow for increased classroom capacity and support in-person learning. In the pre-Delta variant period, limited physical distancing (<6 ft) among students in K-12 schools was not associated with increased SARS-CoV-2 transmission.

      16. Kathryn V. Holmes: A career of contributions to the coronavirus field
        Bonavia A, Dominguez SR, Dveksler G, Gagneten S, Howard M, Jeffers S, Qian Z, Smith MK, Thackray LB, Tresnan DB, Wentworth DE, Wessner DR, Williams RK, Miura TA.
        Viruses. 2022 Jul 20;14(7).
        Over the past two years, scientific research has moved at an unprecedented rate in response to the COVID-19 pandemic. The rapid development of effective vaccines and therapeutics would not have been possible without extensive background knowledge on coronaviruses developed over decades by researchers, including Kathryn (Kay) Holmes. Kay's research team discovered the first coronavirus receptors for mouse hepatitis virus and human coronavirus 229E and contributed a wealth of information on coronaviral spike glycoproteins and receptor interactions that are critical determinants of host and tissue specificity. She collaborated with several research laboratories to contribute knowledge in additional areas, including coronaviral pathogenesis, epidemiology, and evolution. Throughout her career, Kay was an extremely dedicated and thoughtful mentor to numerous graduate students and post-doctoral fellows. This article provides a review of her contributions to the coronavirus field and her exemplary mentoring.

    • Community Health Services
      1. Keeping healthcare linens clean: Underrecognized hazards and critical control points to avoid contamination of laundered healthcare textiles
        Glowicz J, Benowitz I, Arduino MJ, Li R, Wu K, Jordan A, Toda M, Garner K, Gold JA.
        Am J Infect Control. 2022 Jul 19.
        Outbreaks of healthcare-associated infections, particularly invasive mold infections, have been linked to environmental contamination of laundered healthcare textiles. Contamination may occur at the laundry or healthcare facility. This report highlights underrecognized hazards, control points, and actions that infection preventionists can take to help decrease the potential for patient exposure to contaminated healthcare textiles. Infection preventionists can use the checklists included in this report to assess laundry and healthcare facility management of laundered healthcare textiles.

      2. Body lice among people experiencing homelessness and access to hygiene services during the COVID-19 pandemic-preventing trench fever in Denver, Colorado, 2020
        Marshall KE, Martinez HE, Woodall T, Guerrero A, Mechtenberg J, Herlihy R, House J.
        Am J Trop Med Hyg. 2022 Jul 5.
        Eight people with human body louse-borne Bartonella quintana infections were detected among people experiencing homelessness (PEH) in Denver during January-September 2020, prompting a public health investigation and community outreach. Public health officials conducted in-person interviews with PEH to more fully quantify body lice prevalence, transmission risk factors, access to PEH resources, and how the COVID-19 pandemic has affected resource access. Recent body lice exposure was reported by 35% of 153 interview participants. In total, 75% of participants reported reduced access to PEH services, including essential hygiene activities to prevent body lice, during Colorado's COVID-19 stay-at-home orders. Future pandemic planning should consider hygiene resource allocation for PEH populations to prevent emerging and reemerging infections such as B. quintana.

      3. Staff involvement and family and community engagement
        Webster CA, Hoke A, Cornett K, Goh TL, Pulling Kuhn A.
        J Phys Educ, Recreation and Dance. 2022 ;93(5):27-34.
        The staff involvement (SI) and family and community engagement (FCE) components of the CSPAP framework constitute the support system for program implementation and sustainability. These components embody the essence of the framework because they focus on the coordination and synergy needed for a successful program, and such attributes are the hallmark of multicomponent approaches to school-based health promotion. But what does it take to galvanize school staff, families, and communities in a collective effort to bolster quality physical education and promote and increase the physical activity (PA) of children and adolescents? In this article, the authors summarize research on SI and FCE, particularly over the past decade. While research on these CSPAP components is still in its emergent stages, we identify key findings to date and suggest strategies for translating research to practice. It is our hope that this article will provide school PA leaders (PALs) and physical education teacher educators with actionable ideas to more fully leverage the CSPAP support system. © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

    • Disaster Preparedness and Emergency Services
      1. Of masks and methylene blue—The use of methylene blue photochemical treatment to decontaminate surgical masks contaminated with a tenacious small nonenveloped norovirus
        Wielick C, Fries A, Dams L, Razafimahefa R, Heyne B, Harcourt B, Lendvay T, Willaert J, de Jaeger S, Haubruge E, Thiry E, Ludwig-Begall L.
        Am J Infect Control. 2022 ;50(8):871-877.
        • PPE reuse necessitates reliable respiratory and oral human pathogen decontamination. • Equitable decontamination technologies must be available in low-resource settings. • Methylene blue photochemical treatment decontaminates noroviruses on surgical masks. • Norovirus inactivation predicts inactivation of any less resistant viral contaminant. • Role of low-cost – low-tech photochemical decontamination in pandemic preparedness. In the context of the SARS-CoV-2 pandemic, reuse of personal protective equipment, specifically that of medical face coverings, has been recommended. The reuse of these typically single-use only items necessitates procedures to inactivate contaminating human respiratory and gastrointestinal pathogens. We previously demonstrated decontamination of surgical masks and respirators contaminated with infectious SARS-CoV-2 and various animal coronaviruses via low concentration- and short exposure methylene blue photochemical treatment (10 µM methylene blue, 30 minutes of 12,500-lux red light or 50,000 lux white light exposure). Here, we describe the adaptation of this protocol to the decontamination of a more resistant, non-enveloped gastrointestinal virus and demonstrate efficient photodynamic inactivation of murine norovirus, a human norovirus surrogate. Methylene blue photochemical treatment (100 µM methylene blue, 30 minutes of 12,500-lux red light exposure) of murine norovirus-contaminated masks reduced infectious viral titers by over four orders of magnitude on surgical mask surfaces. Inactivation of a norovirus, the most difficult to inactivate of the respiratory and gastrointestinal human viruses, can predict the inactivation of any less resistant viral mask contaminant. The protocol developed here thus solidifies the position of methylene blue photochemical decontamination as an important tool in the package of practical pandemic preparedness.

      2. Evaluation of community perceptions and prevention practices related to ebola virus as part of outbreak preparedness in Uganda, 2020
        Musaazi J, Namageyo-Funa A, Carter VM, Carter RJ, Lamorde M, Apondi R, Bakyaita T, Boore AL, Brown VR, Homsy J, Kigozi J, Koyuncu A, Nabaggala MS, Nakate V, Nkurunziza E, Stowell DF, Walwema R, Olowo A, Jalloh MF.
        Glob Health Sci Pract. 2022 ;10(3).
        Introduction: During the 2018–2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo, risk communication and community engagement (RCCE) were prioritized in geographic areas in Uganda considered at high risk of introduction of EVD. To inform EVD preparedness in Uganda, we evaluated community perceptions and prevention practices related to EVD in 6 districts in Uganda. Methods: In March 2020, we conducted a population-based survey in 6 purposively selected districts in Uganda using multistage cluster sampling. We examined differences between districts classified as high- versus low risk for EVD in terms of their message exposure from RCCE; risk perception; and EVD knowledge, attitudes, and prevention practices. Results: A total of 3,485 respondents were interviewed (91% response rate). EVD message exposure was more common in the high- versus low-risk districts. EVD risk perceptions were low overall but greater in the high- versus low-risk districts. Comprehensive knowledge was significantly greater in the high- versus low-risk districts (adjusted prevalence ratio [aPR] 1.61, 95% confidence interval [CI]=1.35, 1.93). Respondents’ engagement in all 3 EVD prevention practices (frequent handwashing with soap, avoiding physical contact with suspected Ebola patients, and avoiding burials involving contact with a corpse) was very low (4%). However, respondents with comprehensive knowledge were more likely to engage in all 3 EVD prevention practices compared to respondents without comprehensive knowledge (aPR 1.87, 95% CI=1.08, 3.25). Conclusion: Our findings suggest that while RCCE efforts as part of EVD outbreak preparedness may have contributed to higher EVD knowledge in the targeted high-risk districts, uptake of prevention behaviors was similarly low across districts. In a non-outbreak setting, implementing targeted RCCE strategies may not be sufficient to motivate people to adopt protective behaviors in the absence of a high threshold of perceived threat such as in an active outbreak. © Musaazi et al.

    • Epidemiology and Surveillance
      1. CaFÉ: A sensitive, low-cost filtration method for detecting polioviruses and other enteroviruses in residual waters
        Belgasmi H, Miles SJ, Sayyad L, Wong K, Harrington C, Gerloff N, Coulliette-Salmond AD, Guntapong R, Tacharoenmuang R, Ayutthaya AI, Apostol LN, Valencia ML, Burns CC, Benito GR, Vega E.
        Front Environ Sci. 2022 ;10.
        Acute flaccid paralysis (AFP) surveillance has been used to identify polio cases and target vaccination campaigns since the inception of the Global Poliovirus Eradication Initiative (GPEI) in 1988. To date, only Afghanistan and Pakistan have failed to interrupt wild poliovirus transmission. Circulation of vaccine-derived polioviruses (VDPV) continues to be a problem in high-risk areas of the Eastern Mediterranean, African, and Southeast Asian regions. Environmental surveillance (ES) is an important adjunct to AFP surveillance, helping to identify circulating polioviruses in problematic areas. Stools from AFP cases and contacts (>200,000 specimens/year) and ES samples (>642 sites) are referred to 146 laboratories in the Global Polio Laboratory Network (GPLN) for testing. Although most World Health Organization supported laboratories use the two-phase separation method due to its simplicity and effectiveness, alternative simple, widely available, and cost-effective methods are needed. The CAFÉ (Concentration and Filtration Elution) method was developed from existing filtration methods to handle any type of sewage or residual waters. At $10–20 US per sample for consumable materials, CAFÉ is cost effective, and all equipment and reagents are readily available from markets and suppliers globally. The report describes the results from a parallel study of CAFÉ method with the standard two-phase separation method. The study was performed with samples collected from five countries (Guatemala, Haïti, Thailand, Papua New Guinea, and the Philippines), run in three laboratories–(United States, Thailand and in the Philippines) to account for regional and sample-to-sample variability. Samples from each site were divided into two 500 ml aliquots and processed by both methods, with no other additional concentration or manipulation. The results of 338 parallel-tested samples show that the CAFÉ method is more sensitive than the two-phase separation method for detection of non-polio enteroviruses (p-value < 0.0001) and performed as well as the two-phase separation method for polioviruses detection with no significant difference (p-value > 0.05). The CAFÉ method is a robust, sensitive, and cost-effective method for isolating enteroviruses from residual waters. Copyright © 2022 Belgasmi, Miles, Sayyad, Wong, Harrington, Gerloff, Coulliette-Salmond, Guntapong, Tacharoenmuang, Ayutthaya, Apostol, Valencia, Burns, Benito and Vega.

      2. Delayed outbreak detection: a wake-up call to evaluate a surveillance system
        Bulage L, Kadobera D, Kwesiga B, Kabwama SN, Ario AR, Harris JR.
        Pan Afr Med J. 2022 ;41.
        During May, 83 of the 120 districts in Uganda had reported malaria cases above the upper limit of the normal channel. Across all districts, cases had exceeded malaria normal channel upper limits for an average of six months. Yet no alarms had been raised! Starting in 2000, Uganda adopted the World Health Organization (WHO) Integrated Disease Surveillance and Response (IDSR) strategy for disease reporting, including for malaria. Even early on, however, it was unclear how effectively IDSR and DHIS2 were being used in Uganda. Outbreaks were consistently detected late, but the underlying cause of the late detection was unclear. Suspecting there might be gaps in the surveillance system that were not immediately obvious, the Uganda FETP was asked to evaluate the malaria surveillance system in Uganda. This case study teaches trainees in Field Epidemiology and Laboratory Training Programs, public health students, public health workers who may participate in evaluation of public health surveillance systems, and others who are interested in this topic on reasons, steps, and attributes and uses the surveillance evaluation approach to identify gaps and facilitates discussion of practical solutions for improving a public health surveillance system. © Lilian Bulage et al.

      3. How do we…form and coordinate a national serosurvey of SARS-CoV-2 within the blood collection industry?
        Fink RV, Fisher L, Sulaeman H, Dave H, Levy ME, McCann L, Di Germanio C, Notari EP, Green V, Cyrus S, Williamson P, Saa P, Haynes JM, Groves J, Mathew S, Kaidarova Z, Bruhn R, Grebe E, Opsomer J, Jones JM, Miller MJ, Busch MP, Stone M.
        Transfusion. 2022 Jul;62(7):1321-1333.
        BACKGROUND: A national serosurvey of U.S. blood donors conducted in partnership with the Centers for Disease Control and Prevention (CDC) was initiated to estimate the prevalence of SARS-CoV-2 infections and vaccinations. METHODS: Beginning in July 2020, the Nationwide Blood Donor Seroprevalence Study collaborated with multiple blood collection organizations, testing labs, and leadership from government partners to capture, test, and analyze approximately 150,000 blood donation specimens per month in a repeated, cross-sectional seroprevalence survey. RESULTS: A CDC website (https://covid.cdc.gov/covid-data-tracker/#nationwide-blood-donor-seroprevalence) provided stratified, population-level results to public health professionals and the general public. DISCUSSION: The study adapted operations as the pandemic evolved, changing specimen flow and testing algorithms, and collecting additional data elements in response to changing policies on universal blood donation screening and administration of SARS-CoV-2 spike-based vaccines. The national serosurvey demonstrated the utility of serosurveillance testing of residual blood donations and highlighted the role of the blood collection industry in public-private partnerships during a public health emergency.

    • Food Safety
      1. A 2019 outbreak investigation of hepatitis A virus infections in the United States linked to imported fresh blackberries
        McClure M, Nsubuga J, Montgomery MP, Jenkins E, Crosby A, Schoelen D, Basler C, Ramachandran S, Lin Y, Xia GL, Khudaykov Y, Suktankar V, Wagley A, Thomas V, Woods J, Hintz L, Oliveira J, Sandoval AL, Frederick J, Hendrickson B, Gieraltowski L, Viazis S.
        Food Environ Virol. 2022 Jul 23.
        Globally, hepatitis A virus (HAV) is one of the most common agents of acute viral hepatitis and causes approximately 1.4 million cases and 90,000 deaths annually despite the existence of an effective vaccine. In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh blackberries sourced from multiple suppliers in Michoacán, Mexico. A total of 20 individuals with outbreak-related HAV infection were reported in seven states, including 11 hospitalizations, and no deaths. The Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and Nebraska State and Douglas County Health Departments conducted a traceback investigation for fresh blackberries reportedly purchased by 16 ill persons. These individuals reported purchasing fresh blackberries from 11 points of service from September 16 through 29, 2019 and their clinical isolates assessed through next-generation sequencing and phylogenetic analysis were genetically similar. The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, but all of the blackberries were harvested from growers in Michoacán, Mexico. FDA did not detect the pathogen after analyzing fresh blackberry samples from four distributors, one consumer, and from nine importers at the port of entry as a result of increased screening. Challenges included gaps in traceability practices and the inability to recover the pathogen from sample testing, which prohibited investigators from determining the source of the implicated blackberries. This multi-state outbreak illustrated the importance of food safety practices for fresh produce that may contribute to foodborne illness outbreaks.

    • Genetics and Genomics
      1. Sequencing of enteric bacteria: Library preparation procedure matters for accurate identification and characterization
        Poates A, Truong J, Lindsey R, Griswold T, Williams-Newkirk AJ, Carleton H, Trees E.
        Foodborne Pathog Dis. 2022 Jul 21.
        Enzymatic library preparation kits are increasingly used for bacterial whole genome sequencing. While they offer a rapid workflow, the transposases used in the kits are recognized to be somewhat biased. The aim of this study was to optimize and validate a protocol for the Illumina DNA Prep kit (formerly Nextera DNA Flex) for sequencing enteric pathogens and compare its performance against the Nextera XT kit. One hundred forty-three strains of Campylobacter, Escherichia, Listeria, Salmonella, Shigella, and Vibrio were prepared with both methods and sequenced on the Illumina MiSeq using 300 and/or 500 cycle chemistries. Sequences were compared using core genome multilocus sequence typing (cgMLST), 7-gene multilocus sequence typing (MLST), and detection of markers encoding serotype, virulence, and antimicrobial resistance. Sequences for one Escherichia strain were downsampled to determine the minimum coverage required for the analyses. While organism-specific differences were observed, the Prep libraries generated longer average read lengths and less fragmented assemblies compared to the XT libraries. In downstream analysis, the most notable difference between the kits was observed for Escherichia, particularly for the 300 cycle sequences. The O group was not predicted in 32% and 4% of XT sequences when using blast and kmer algorithms, respectively, while the O group was predicted from all Prep sequences regardless of the algorithm. In addition, the ehxA gene was not detected in 6% of XT sequences and 34% were missing one or more of the type III secretion systems and/or plasmid-associated genes, which were detected in the Prep sequences. The coverage downsampling revealed that acceptable assembly quality and allele detection was achieved at 30 × coverage with the Prep libraries, whereas 40-50 × coverage was required for the XT libraries. The better performance of the Prep libraries was attributed to more even coverage, particularly in genome regions low in GC content.

    • Health Equity and Health Disparities
      1. Neighborhood socioeconomic deprivation in early childhood mediates racial disparities in blood pressure in a college student sample
        Nichols OI, Fuller-Rowell TE, Robinson AT, Eugene D, Homandberg LK.
        J Youth Adolesc. 2022 Jul 19.
        The influence of childhood contexts on adult blood pressure is an important yet understudied topic. Using a developmental perspective, this study examines the association between neighborhood socioeconomic disadvantage in early childhood (0-5 yrs), middle childhood (6-12 yrs) and adolescence (13-18 yrs) on subsequent blood pressure in young adulthood. Data were from 263 college students (52% Black; M(age) = 19.21 years) and neighborhood socioeconomic disadvantage was measured using a tract-level Area Deprivation Index. Neighborhood disadvantage in early childhood was significantly associated with diastolic blood pressure and explained 22% of the race difference between Black and White adults. The findings are consistent with the notion that early childhood may be a sensitive period for the effects of neighborhood disadvantage on blood pressure.

      2. Increasing the resolution and broadening the focus on childhood asthma disparities
        Akinbami LJ, Bryant-Stephens T.
        Pediatrics. 2022 Jul 25.

    • Healthcare Associated Infections
      1. Transfusion-transmitted Cache Valley virus infection in a kidney transplant recipient with meningoencephalitis
        Al-Heeti O, Wu EL, Ison MG, Saluja RK, Ramsey G, Matkovic E, Ha K, Hall S, Banach B, Wilson MR, Miller S, Chiu CY, McCabe M, Bari C, Zimler RA, Babiker H, Freeman D, Popovitch J, Annambhotla P, Lehman JA, Fitzpatrick K, Velez JO, Davis EH, Hughes HR, Panella A, Brault A, Erin Staples J, Gould CV, Tanna S.
        Clin Infect Dis. 2022 Jul 27.
        BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the Fall of 2020, a patient developed encephalitis six weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens by reverse transcription-polymerase chain reaction (RT-PCR), plaque reduction neutralization test (PRNT), cell culture, and whole genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSION: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS testing might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

      2. Establishing a standardized surveillance system for health care-associated infections in Vietnam
        Coker D, Phuong HT, Nguyen LT, Ninh T, Gupta N, Ha TT, Truong NT, Van Thanh H, Vasquez A, Bui HT, Malpiedi P.
        Glob Health Sci Pract. 2022 ;10(3).
        Standardized surveillance for health care-associated infections (HAI) is critical to understand HAI burden and inform prevention strategies at a national level. Due to differing and generally limited resources in Vietnam’s health care facilities, implementation of HAI surveillance has been variable and data quality has not been systematically assessed. In 2016, the Vietnam Administration for Medical Services (VAMS) under the Ministry of Health, with the support of partners, began to establish a context-appropriate, standardized HAI surveillance system for bloodstream infections (BSI) and urinary tract infections (UTI) among 6 pilot hospitals in Vietnam. We identified 5 key elements of our HAI surveillance implementation process that have been conducive to ensuring data quality and program sustainability and scalability. These include: (1) engaging stakeholders, (2) designating roles and responsibilities, (3) developing context-sensitive, standardized surveillance protocols, (4) creating a surveillance implementation strategy, and (5) linking HAI surveillance and prevention activities. With the active participation of infection prevention and control staff from the 6 pilot hospitals, standardized HAI surveillance for BSIs and UTIs was expanded to 12 additional hospitals in 2019. Together, VAMS and partners are helping Vietnam fulfill its commitment to safe health care for all patients. © Coker et al.

      3. Risk of severe acute respiratory syndrome coronavirus 2 transmission through solid organ transplantation and outcomes of coronavirus disease 2019 among recent transplant recipients
        Free RJ, Annambhotla P, La Hoz RM, Danziger-Isakov L, Jones JM, Wang L, Sankthivel S, Levi ME, Michaels MG, Kuhnert W, Klassen D, Basavaraju SV, Kracalik IT.
        Open Forum Infect Dis. 2022 Jul;9(7):ofac221.
        BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmissible through lung transplantation, and outcomes among infected organ recipients may be severe. Transmission risk to extrapulmonary organ recipients and recent (within 30 days of transplantation) SARS-CoV-2-infected recipient outcomes are unclear. METHODS: During March 2020-March 2021, potential SARS-CoV-2 transmissions through solid organ transplantation were investigated. Assessments included SARS-CoV-2 testing, medical record review, determination of likely transmission route, and recent recipient outcomes. RESULTS: During March 2020-March 2021, approximately 42 740 organs were transplanted in the United States. Forty donors, who donated 140 organs to 125 recipients, were investigated. Nine (23%) donors and 25 (20%) recipients were SARS-CoV-2 positive by nucleic acid amplification test (NAAT). Most (22/25 [88%]) SARS-CoV-2-infected recipients had healthcare or community exposures. Nine SARS-CoV-2-infected donors donated 21 organs to 19 recipients. Of these, 3 lung recipients acquired SARS-CoV-2 infections from donors with negative SARS-CoV-2 testing of pretransplant upper respiratory tract specimens but from whom posttransplant lower respiratory tract (LRT) specimens were SARS-CoV-2 positive. Sixteen recipients of extrapulmonary organs from SARS-CoV-2-infected donors had no evidence of posttransplant COVID-19. All-cause mortality within 45 days after transplantation was 6-fold higher among SARS-CoV-2-infected recipients (9/25 [36%]) than those without (6/100 [6%]). CONCLUSIONS: Transplant-transmission of SARS-CoV-2 is uncommon. Pretransplant NAAT of lung donor LRT specimens may prevent transmission of SARS-CoV-2 through transplantation. Extrapulmonary organs from SARS-CoV-2-infected donors may be safely usable, although further study is needed. Reducing recent recipient exposures to SARS-CoV-2 should remain a focus of prevention.

    • Immunity and Immunization
      1. COVID-19 vaccination and intent for vaccination of adults with reported medical conditions
        Lu PJ, Hung MC, Jackson HL, Kriss JL, Srivastav A, Yankey D, Santibanez TA, Lee JT, Meng L, Razzaghi H, Black CL, Elam-Evans LD, Singleton JA.
        Am J Prev Med. 2022 Jun 27.
        INTRODUCTION: Individuals with certain medical conditions are at substantially increased risk for severe illness from COVID-19. The purpose of this study is to assess COVID-19 vaccination among U.S. adults with reported medical conditions. METHODS: Data from the National Immunization Survey-Adult COVID Module collected during August 1-September 25, 2021 were analyzed in 2022 to assess COVID-19 vaccination status, intent, vaccine confidence, behavior, and experience among adults with reported medical conditions. Unadjusted and age-adjusted prevalence ratios (PRs and APRs) were generated using logistic regression and predictive marginals. RESULTS: Overall, COVID-19 vaccination coverage with ≥1 dose was 81.8% among adults with reported medical conditions, and coverage was significantly higher compared with those without such conditions (70.3%) Among adults aged ≥18 years with medical conditions, COVID-19 vaccination coverage was significantly higher among those with a provider recommendation (86.5%) than those without (76.5%). Among all respondents, 9.2% of unvaccinated adults with medical conditions reported they were willing or open to vaccination. Adults who reported high risk medical conditions were more likely to report receiving a provider recommendation, often or always wearing masks during the last 7 days, concerning about getting COVID-19, thinking the vaccine is safe, and believing a COVID-19 vaccine is important for protection from COVID-19 infection than those without such conditions. CONCLUSIONS: Approximately 18.0% of those with reported medical conditions were unvaccinated. Receiving a provider recommendation was significantly associated with vaccination, reinforcing that provider recommendation is an important approach to increase vaccination coverage. Ensuring access to vaccine, addressing vaccination barriers, and increasing vaccine confidence can improve vaccination coverage among unvaccinated adults.

      2. COVID-19 vaccination intention in a community cohort in Ponce, Puerto Rico
        Sánchez-González L, Major CG, Rodriguez DM, Balajee A, Ryff KR, Lorenzi O, Linares M, Adams LE, Rivera-Amill V, Rolfes M, Paz-Bailey G.
        Am J Trop Med Hyg. 2022 Jul 11.
        As of January 20, 2022, > 247,000 confirmed COVID-19 cases and 3,400 deaths were reported in Puerto Rico (PR). We interviewed participants aged ≥ 14 years in the Communities Organized to Prevent Arboviruses (COPA) study, a community-based cohort in PR, about COVID-19 vaccine intention from November 12, 2020, to June 25, 2021. We used univariate and adjusted analyses to identify participant characteristics associated with vaccine intention. Among 1,542 respondents, the median age was 37 years (interquartile range 23-45) and 914 (59%) were female. Most participants (83%) reported a willingness to receive a COVID-19 vaccine. The most common reason for vaccine hesitancy was concern about the safety or side effects (64%). Willingness to receive the COVID-19 vaccine was associated with a later interview date, higher household income, previous COVID-19 diagnosis among household members, COVID-19 risk perception, influenza vaccine uptake, dengue vaccine intention, and general positive perceptions of vaccines. While parents with minors (< 21 years old) were less likely to report vaccine intention for themselves than participants without minor children, we observed similar characteristics associated with parents' willingness to vaccinate their children. Overall, COVID-19 vaccine intention was high among COPA participants. It is important that public health messaging in PR addresses COVID-19 vaccine safety and possible side effects.

      3. Autopsy histopathologic cardiac findings in 2 adolescents following the second COVID-19 vaccine dose
        Paddock CD, Reagan-Steiner S, Su JR, Oster ME, Martines RB, Bhatnagar J, Shimabukuro TT.
        Arch Pathol Lab Med. 2022 Aug 1;146(8):921-923.

      4. Sustained within-season vaccine effectiveness against influenza-associated hospitalization in children: Evidence from the New Vaccine Surveillance Network, 2015-2016 through 2019-2020
        Sahni LC, Naioti EA, Olson SM, Campbell AP, Michaels MG, Williams JV, Staat MA, Schlaudecker EP, McNeal MM, Halasa NB, Stewart LS, Chappell JD, Englund JA, Klein EJ, Szilagyi PG, Weinberg GA, Harrison CJ, Selvarangan R, Schuster JE, Azimi PH, Singer MN, Avadhanula V, Piedra PA, Munoz FM, Patel MM, Boom JA.
        Clin Infect Dis. 2022 Jul 22.
        BACKGROUND: Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited. METHODS: We conducted a prospective, test-negative study of children 6 months-17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% x (1 - odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression. RESULTS: Of 8,430 children, 4,653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were vaccinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs. 57%, p < 0.001); overall VE against hospitalization was 53% (95% CI: 46%-60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%-12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4,000, p = 0.275). Odds of hospitalization increased 2.9% (95% CI: -5.4%-11.8%) and 9.6% (95% CI: -7.0%-29.1%) per month in children ≤8 years (n = 3,084) and 9-17 years (n = 916), respectively. These findings were not statistically significant. CONCLUSIONS: We observed minimal, not statistically significant within-season declines in VE. Vaccination following current ACIP guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.

      5. Effectiveness of 2, 3, and 4 COVID-19 mRNA vaccine doses among immunocompetent adults during periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 sublineages predominated - VISION Network, 10 States, December 2021-June 2022
        Link-Gelles R, Levy ME, Gaglani M, Irving SA, Stockwell M, Dascomb K, DeSilva MB, Reese SE, Liao IC, Ong TC, Grannis SJ, McEvoy C, Patel P, Klein NP, Hartmann E, Stenehjem E, Natarajan K, Naleway AL, Murthy K, Rao S, Dixon BE, Kharbanda AB, Akinseye A, Dickerson M, Lewis N, Grisel N, Han J, Barron MA, Fadel WF, Dunne MM, Goddard K, Arndorfer J, Konatham D, Valvi NR, Currey JC, Fireman B, Raiyani C, Zerbo O, Sloan-Aagard C, Ball SW, Thompson MG, Tenforde MW.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 22;71(29):931-939.
        The Omicron variant (B.1.1.529) of SARS-CoV-2, the virus that causes COVID-19, was first identified in the United States in November 2021, with the BA.1 sublineage (including BA.1.1) causing the largest surge in COVID-19 cases to date. Omicron sublineages BA.2 and BA.2.12.1 emerged later and by late April 2022, accounted for most cases.* Estimates of COVID-19 vaccine effectiveness (VE) can be reduced by newly emerging variants or sublineages that evade vaccine-induced immunity (1), protection from previous SARS-CoV-2 infection in unvaccinated persons (2), or increasing time since vaccination (3). Real-world data comparing VE during the periods when the BA.1 and BA.2/BA.2.12.1 predominated (BA.1 period and BA.2/BA.2.12.1 period, respectively) are limited. The VISION network(†) examined 214,487 emergency department/urgent care (ED/UC) visits and 58,782 hospitalizations with a COVID-19-like illness(§) diagnosis among 10 states during December 18, 2021-June 10, 2022, to evaluate VE of 2, 3, and 4 doses of mRNA COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) compared with no vaccination among adults without immunocompromising conditions. VE against COVID-19-associated hospitalization 7-119 days and ≥120 days after receipt of dose 3 was 92% (95% CI = 91%-93%) and 85% (95% CI = 81%-89%), respectively, during the BA.1 period, compared with 69% (95% CI = 58%-76%) and 52% (95% CI = 44%-59%), respectively, during the BA.2/BA.2.12.1 period. Patterns were similar for ED/UC encounters. Among adults aged ≥50 years, VE against COVID-19-associated hospitalization ≥120 days after receipt of dose 3 was 55% (95% CI = 46%-62%) and ≥7 days (median = 27 days) after a fourth dose was 80% (95% CI = 71%-85%) during BA.2/BA.2.12.1 predominance. Immunocompetent persons should receive recommended COVID-19 booster doses to prevent moderate to severe COVID-19, including a first booster dose for all eligible persons and second booster dose for adults aged ≥50 years at least 4 months after an initial booster dose. Booster doses should be obtained immediately when persons become eligible.(¶).

      6. Influenza activity and composition of the 2022-23 influenza vaccine - United States, 2021-22 season
        Merced-Morales A, Daly P, Abd Elal AI, Ajayi N, Annan E, Budd A, Barnes J, Colon A, Cummings CN, Iuliano AD, DaSilva J, Dempster N, Garg S, Gubareva L, Hawkins D, Howa A, Huang S, Kirby M, Kniss K, Kondor R, Liddell J, Moon S, Nguyen HT, O'Halloran A, Smith C, Stark T, Tastad K, Ujamaa D, Wentworth DE, Fry AM, Dugan VG, Brammer L.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 22;71(29):913-919.
        Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

      7. Implementing the COVID-19 Rapid Community Assessment on Vaccine Confidence: Lessons learned from Alabama and Georgia
        Kobau R, Carry M, Rubenstein BL, Denson D, Uribe C, Zajac J, Kidder DP, Peacock G, Abad N.
        Public Health Rep. 2022 Jul 21:333549221112610.
        Engaging communities is a key strategy to increase COVID-19 vaccination. The Centers for Disease Control and Prevention (CDC) COVID-19 Vaccine Confidence Rapid Community Assessment Guide was developed for community partners to obtain insights about barriers to COVID-19 vaccine uptake and to engage community partners in designing interventions to build vaccine confidence. In spring 2021, 3 CDC teams were deployed to Alabama and Georgia to conduct a rapid community assessment in selected jurisdictions. Data collection included interviews, listening sessions, observations, and street intercept surveys. We identified 3 facilitators and barriers to vaccine uptake: (1) planning and coordination, (2) capacity and implementation, and (3) attitudes and beliefs. We found that the use of the rapid community assessment in Alabama and Georgia was feasible to implement, useful in eliciting unique community concerns and dispelling assumptions, and useful in informing intervention strategies. Our results underscore the importance of community engagement in COVID-19 mitigation strategies.

    • Informatics
      1. How well do ICD-9-CM codes predict true congenital heart defects? A Centers For Disease Control And Prevention-based multisite validation project
        Rodriguez FH, Raskind-Hood CL, Hoffman T, Farr SL, Glidewell J, Li JS, D'Ottavio A, Botto L, Reeder MR, Hsu D, Lui GK, Sullivan AM, Book WM.
        J Am Heart Assoc. 2022 Jul 19:e024911.
        Background The Centers for Disease Control and Prevention's Surveillance of Congenital Heart Defects Across the Lifespan project uses large clinical and administrative databases at sites throughout the United States to understand population-based congenital heart defect (CHD) epidemiology and outcomes. These individual databases are also relied upon for accurate coding of CHD to estimate population prevalence. Methods and Results This validation project assessed a sample of 774 cases from 4 surveillance sites to determine the positive predictive value (PPV) for identifying a true CHD case and classifying CHD anatomic group accurately based on 57 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Chi-square tests assessed differences in PPV by CHD severity and age. Overall, PPV was 76.36% (591/774 [95% CI, 73.20-79.31]) for all sites and all CHD-related ICD-9-CM codes. Of patients with a code for complex CHD, 89.85% (177/197 [95% CI, 84.76-93.69]) had CHD; corresponding PPV estimates were 86.73% (170/196 [95% CI, 81.17-91.15]) for shunt, 82.99% (161/194 [95% CI, 76.95-87.99]) for valve, and 44.39% (83/187 [95% CI, 84.76-93.69]) for "Other" CHD anatomic group (X(2)=142.16, P<0.0001). ICD-9-CM codes had higher PPVs for having CHD in the 3 younger age groups compared with those >64 years of age, (X(2)=4.23, P<0.0001). Conclusions While CHD ICD-9-CM codes had acceptable PPV (86.54%) (508/587 [95% CI, 83.51-89.20]) for identifying whether a patient has CHD when excluding patients with ICD-9-CM codes for "Other" CHD and code 745.5, further evaluation and algorithm development may help inform and improve accurate identification of CHD in data sets across the CHD ICD-9-CM code groups.

    • Injury and Violence
      1. Symptoms of mental health conditions and suicidal ideation among state, tribal, local, and territorial public health workers - United States, March 14-25, 2022
        Koné A, Horter L, Thomas I, Byrkit R, Lopes-Cardozo B, Rao CY, Rose C.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 22;71(29):925-930.
        An increase in adverse mental health symptoms occurred in the general population at the onset of the COVID-19 pandemic, which peaked in 2020 and subsequently decreased (1-3). The pandemic exacerbated existing stress and fatigue among public health workers responding to the public health crisis.* During March-April 2021, a survey of state, tribal, local, and territorial (STLT) public health workers found that 52.8% of respondents experienced symptoms of at least one of the following mental health conditions: depression, anxiety, or posttraumatic stress disorder (PTSD) (4); however, more recent estimates of mental health symptoms among this population are limited. To evaluate trends in these conditions from the previous year, the prevalence of symptoms of mental health conditions and suicidal ideation, a convenience sample of STLT public health workers was surveyed during March 14-25, 2022. In total, 26,069 STLT public health workers responded to the survey. Among respondents,(†) 6,090 (27.7%) reported symptoms of depression, 6,467 (27.9%) anxiety, 6,324 (28.4%) PTSD, and 1,853 (8.1%) suicidal ideation. Although the prevalences of depression, anxiety, and PTSD among public health workers were lower (p<0.001)(§) among 2022 survey respondents compared with those of 2021 survey respondents (4), the prevalences of symptoms of suicidal ideation, anxiety, depression, and PTSD remained high among those who worked >60 hours per week (range = 11.3%-45.9%) and those who spent ≥76% of their work time on COVID-19 response activities (range = 9.0%-37.6%). Respondents were less likely to report mental health symptoms if they could take time off (prevalence ratio [PR] range = 0.48-0.55), or if they perceived an increase in mental health resources from their employer (PR range = 0.58-0.84). To support the mental health of public health workers, public health agencies can modify work-related factors, including making organizational changes for emergency responses and facilitating access to mental health resources and services.(¶).

    • Laboratory Sciences
      1. Exploring inactivation of SARS-CoV-2, MERS-CoV, Ebola, Lassa, and Nipah viruses on N95 and KN95 respirator material using photoactivated methylene blue to enable reuse
        Scholte FM, Kabra K, Tritsch S, Montgomery J, Spiropoulou C, Mores C, Harcourt B.
        Am J Infect Control. 2022 ;50(8):863-870.
        • The photoactivated dye methylene blue inactivates many human pathogens. • The technique inactivates SARS-CoV-2, Ebola, Lassa and Nipah viruses on respirators. • Decontamination of N95 and KN95 respirators allows safe limited reuse. • Methylene blue can be used for pretreatment and decontamination of respirators. • Pretreatment of PPE could allow for real-time virus inactivation. The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely reuse PPE. Methylene blue (MB) is a light-activated dye with demonstrated antimicrobial activity used to sterilize blood plasma. Decontamination of respirators using photoactivated MB requires no specialized equipment, making it attractive for use in the field during outbreaks. We examined decontamination of N95 and KN95 respirators using photoactivated MB and 3 variants of SARS-CoV-2, the virus that causes COVID-19; and 4 World Health Organization priority pathogens: Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Lassa virus. Virus inactivation by pretreating respirator material was also tested. Photoactivated MB inactivated all tested viruses on respirator material, albeit with varying efficiency. Virus applied to respirator material pre-treated with MB was also inactivated, thus MB pretreatment may potentially protect respirator wearers from virus exposure in real-time. These results demonstrate that photoactivated MB represents a cost-effective, rapid, and widely deployable method to decontaminate N95 respirators for reuse during supply shortages.

      2. Performance of SARS-CoV-2 antigens in a multiplex bead assay for integrated serological surveillance of neglected tropical and other diseases
        Gwyn S, Abubakar A, Akinmulero O, Bergeron E, Blessing UN, Chaitram J, Coughlin MM, Dawurung AB, Dickson FN, Esiekpe M, Evbuomwan E, Greby SM, Iriemenam NC, Kainulainen MH, Naanpoen TA, Napoloen L, Odoh I, Okoye M, Olaleye T, Schuh AJ, Owen SM, Samuel A, Martin DL.
        Am J Trop Med Hyg. 2022 Jun 27.
        Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic.

      3. An automated high-throughput enterovirus D68 microneutralization assay platform
        Rhoden EE, Mainou BA, Konopka-Anstadt JL, Oberste MS.
        J Virol Methods. 2022 Jul 22:114590.
        Virus neutralization assays, widely used to detect and quantify antibodies induced by virus infection, are considered the gold standard for enterovirus serology testing. Conventional microneutralization assays have been used to assess enterovirus D68 (EV-D68) seroprevalence. While manual or automated 96-well assays are valuable, higher-density assays that increase throughput provide the opportunity to more efficiently screen large, population-based serology collections, as well as to test sample sets against multiple virus strains on the same plate or within the same run. Here, automation was implemented for bulk reagent dispensing, serial dilutions, and luminescence measurement to develop a 384-well enterovirus microneutralization assay that increases overall testing throughput, maintains the reproducibility of the standard 96-well assay, and reduces sample volume usage. EV-D68 strains Fermon, 14-18953, and 18-23087 were used to evaluate the automated 384-well microneutralization assay and compare to the conventional 96-well assay. Sensitivity and specificity were evaluated using pooled human sera and positive and negative control antisera. The Lower Limit of quantitation (LLOQ) was the same as for the 96-well assay and coefficients of variations (CV) of 7.35%, 5.97%, and 2.85% for the three EV-D68 strains respectively, were well below the typical goal of ≤ 20% CV for accuracy. Z-factor analysis yielded results of 0.694, 0.638, and 0.852, for the three EV-D68 strains respectively, indicating a high level of precision, reliability, and robustness. Intra-assay (7.25%) and inter-assay (7.12%) variability were well below 20% CV. Moreover, the 96-well and 384-well versions of the assay were highly concordant, with a 0.955 correlation coefficient in titers obtained for 50 sera tested. Validation of this automated 384-well microneutralization will support its use in large serology screens assessing the presence of EV-D68 neutralizing antibodies in human populations.

    • Maternal and Child Health
      1. Neonatal jaundice: Knowledge and practices of healthcare providers and trainees in Southwest Nigeria
        Barclay E, Ojo I, Hake A, Oyenuga A, Satrom K, Lund T, Oyenuga M, Slusher T, Gbadero D.
        Am J Trop Med Hyg. 2022 Jun 27.
        Severe neonatal jaundice (SNNJ) is a leading cause of neonatal morbidity and mortality in low- and middle-income countries (LMICs). Risk mitigation and management modalities for SNNJ have led to a marked reduction in complications in high-income countries but not in LMICs likely in part due to knowledge gaps among healthcare providers. This study, a cross-sectional study conducted in Ogbomosho, Nigeria, aimed to identify SNNJ knowledge and practices among Nigerian healthcare providers/trainees. Healthcare providers/trainees completed a structured questionnaire. Healthcare providers/trainees included are nurse midwives (33.4%), nurses (18.6%), nursing students (15.2%), traditional birth attendants (TBAs) (12.7%), physicians (10.2%), and medical students (9.9%). Most physicians were aware of the common causes of SNNJ; however, knowledge deficits in other groups were notable. Despite most providers endorsing that glucose-6-phosphate dehydrogenase deficiency can cause SNNJ (91% of physicians, 60% of nurses, 71% of midwives, 81% of medical students, 43% of nursing students, 7% of TBAs), very few providers recognized that it is common, ranging from 3% in nurses up to a high of 47% among medical students. Gaps in provider knowledge regarding preventative measures and sequela were also noted. These data identified significant knowledge gaps regarding the etiology of SNNJ among healthcare providers/trainees, which can lead to missed opportunities in effective prevention and treatment. These deficits must be addressed if we are to eliminate tragic and preventable complications from SNNJ in Nigeria and other LMICs.

      2. Risk of birth defects by pregestational type 1 or type 2 diabetes: National Birth Defects Prevention Study, 1997-2011
        Marchincin SL, Howley MM, Van Zutphen AR, Fisher SC, Nestoridi E, Tinker SC, Browne ML.
        Birth Defects Res. 2022 Jun 6.
        BACKGROUND: Previous studies found consistent associations between pregestational diabetes and birth defects. Given the different biological mechanisms for type 1 (PGD1) and type 2 (PGD2) diabetes, we used National Birth Defects Prevention Study (NBDPS) data to estimate associations by diabetes type. METHODS: The NBDPS was a study of major birth defects that included pregnancies with estimated delivery dates from October 1997 to December 2011. We compared self-reported PGD1 and PGD2 for 29,024 birth defect cases and 10,898 live-born controls. For case groups with ≥5 exposed cases, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between specific defects and each diabetes type. We calculated crude ORs (cORs) and 95% CIs with Firth's penalized likelihood for case groups with 3-4 exposed cases. RESULTS: Overall, 252 (0.9%) cases and 24 (0.2%) control mothers reported PGD1, and 357 (1.2%) cases and 34 (0.3%) control mothers reported PGD2. PGD1 was associated with 22/26 defects examined and PGD2 was associated with 29/39 defects examined. Adjusted ORs ranged from 1.6 to 70.4 for PGD1 and from 1.6 to 59.9 for PGD2. We observed the strongest aORs for sacral agenesis (PGD1: 70.4, 32.3-147; PGD2: 59.9, 25.4-135). For both PGD1 and PGD2, we observed elevated aORs in every body system we evaluated, including central nervous system, orofacial, eye, genitourinary, gastrointestinal, musculoskeletal, and cardiac defects. CONCLUSIONS: We observed positive associations between both PGD1 and PGD2 and birth defects across multiple body systems. Future studies should focus on the role of glycemic control in birth defect risk to inform prevention efforts.

      3. Michigan plan for appropriate tailored healthcare in pregnancy prenatal care recommendations: A practical guide for maternity care clinicians
        Peahl AF, Turrentine M, Barfield W, Blackwell SC, Zahn CM.
        J Womens Health (Larchmt). 2022 Jul;31(7):917-925.
        Prenatal care is an important preventive service designed to improve the health of pregnant patients and their infants. Prenatal care delivery recommendations have remained unchanged since 1930, when the 12-14 in-person visit schedule was first established to detect preeclampsia. In 2020, the American College of Obstetricians and Gynecologists, in collaboration with the University of Michigan, convened a panel of maternity care experts to determine new prenatal care delivery recommendations. The panel recognized the need to include emerging evidence and experience, including significant changes in prenatal care delivery during the COVID-19 pandemic, pre-existing knowledge of the importance of individualized care plans, the promise of telemedicine, and the significant influence of social and structural determinants of health (SSDoH) on pregnancy outcomes. Recommendations were derived using the RAND-UCLA appropriateness method, a rigorous e-Delphi method, and are designed to extend beyond the acute public health crisis. The resulting Michigan Plan for Appropriate Tailored Healthcare in pregnancy (MiPATH) includes recommendations for key aspects of prenatal care delivery: (1) the recommended number of prenatal visits, (2) the frequency of prenatal visits, (3) the role of monitoring routine pregnancy parameters (blood pressure, fetal heart tones, weight, and fundal height), (4) integration of telemedicine into routine care, and (5) inclusion of (SSDoH). Resulting recommendations demonstrate a new approach to prenatal care delivery that incorporates medical, SSDoH, and patient preferences, to develop individualized prenatal care delivery plans. The purpose of this document is to outline the new MiPATH recommendations and to provide practical guidance on implementing them in routine practice.

      4. Hepatitis C virus testing during pregnancy after universal screening recommendations
        Kaufman HW, Osinubi A, Meyer WA, Khan M, Huang X, Panagiotakopoulos L, Thompson WW, Nelson N, Wester C.
        Obstet Gynecol. 2022 Jul 1;140(1):99-101.
        The study evaluates the effect of the 2020 Centers for Disease Control and Prevention and U.S. Preventive Services Task Force recommendations on hepatitis C virus (HCV) screening among pregnant persons nationally and by health insurance type. The study included 5,048,428 pregnant persons aged 15-44 years with either Medicaid or commercial health insurance who had obstetric panel testing performed by Quest Diagnostics, January 2011-June 2021. Antibody screening for HCV infection increased before and accelerated after the updated recommendations in early 2020. Disparities in HCV testing by health insurance status were substantial over the entire study period. Despite substantial progress in the proportion of pregnant persons screened for HCV infection, current testing rates fall short of universal recommendations.

      5. Identifying deaths during and after pregnancy: New approaches to a perennial challenge
        Trost SL, Beauregard J, Petersen EE, Cox S, Chandra G, St Pierre A, Rodriguez M, Goodman D.
        Public Health Rep. 2022 Jul 23:333549221110487.

      6. Supporting parents of adolescents: a powerful and under-utilised opportunity to influence adolescent development
        Skeen S, Ahmad JH, Bachman G, Cluver L, Gardner F, Madrid B, Miller K, Tomlinson M, Sherr L, Levy M.
        Vulnerable Child Youth Stud. 2022 .
        Throughout the rapid and intense changes that adolescents experience, their parents retain important influence over how they interact with the complex factors that shape their development. How parents care for their adolescent children has a deep and lasting impact on their well-being and development. Yet, parents often require support to meet their own and their adolescent children’s needs, which can be achieved through parenting support programmes. Parenting support programmes are delivered to parents of younger children across different contexts and populations, but the benefit of these programmes for parents of adolescents is not well-recognised or prioritised. Given the clear need for these interventions during adolescence and the substantial evidence for effectiveness in this age group, it is time to move the field forward. Increased resources to support parents of adolescents would maximise adolescents’ developmental potential and promote their well-being. We highlight four pressing areas for action: including parents of adolescents in parenting initiatives; involving parents in adolescent programming; strengthening efforts to address poverty and inequality, violence, and gender inequality; and engaging in strategic research to intensify the impact of programming. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

    • Occupational Safety and Health
      1. Serum per- and polyfluoroalkyl substance concentrations in four municipal US fire departments
        Burgess JL, Fisher JM, Nematollahi A, Jung AM, Calkins MM, Graber JM, Grant CC, Beitel SC, Littau SR, Gulotta JJ, Wallentine DD, Hughes RJ, Popp C, Calafat AM, Botelho JC, Coleman AD, Schaefer-Solle N, Louzado-Feliciano P, Oduwole SO, Caban-Martinez AJ.
        Am J Ind Med. 2022 Jul 21.
        BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

      2. Working hours, sleep, and fatigue in the agriculture, forestry, and fishing sector: A scoping review
        Elliott KC, Lincoln JM, Flynn MA, Levin JL, Smidt M, Dzugan J, Ramos AK.
        Am J Ind Med. 2022 Jul 26.
        INTRODUCTION: Agriculture, forestry, and fishing industry (AgFF) workers often work extremely long hours during peak production seasons, resulting in sleep deprivation and fatigue. The National Occupational Research Agenda has classified fatigue as a "significant safety issue" and area of concern for many industry sectors, including AgFF. This review explores current research and practice in AgFF and proposes next steps. METHODS: We conducted a scoping literature review to examine the extent and nature of research in this area. Article inclusion criteria included peer-reviewed journal articles written in English; published after 1989; covering AgFF workers in high-income countries; with data on working hours/schedules and sleep related to safety and health. RESULTS: Limited research has addressed long hours and sleep deprivation among AgFF workers. We identified 8350 articles for title and abstract review. Among those, 407 underwent full-text review and 96 met all inclusion criteria (67% agriculture, 25% fishing/seafood processing, 8% forestry). The literature provided some evidence fatigue contributes to fatalities, injuries, and illnesses in AgFF. Older, new, young, foreign-born, and female workers, as well as those who work in small organizations or longer hours (40+) may be at higher risk for fatigue-related injury and illness. Few studies have developed or evaluated interventions to control risks. DISCUSSION: Given that fatigue is a factor in injury and illness for this sector, future AgFF surveillance and research should increase efforts to capture fatigue and sleep data, directly investigate the role of long hours and nonstandard work schedules in the sector, and most importantly, create practical interventions to manage fatigue.

      3. Workplace violence during the COVID-19 pandemic: March-October, 2020, United States
        Tiesman H, Marsh S, Konda S, Tomasi S, Wiegand D, Hales T, Webb S.
        J Safety Res. 2022 Jul:[Epub ahead of print].
        Problem: COVID-19 has impacted United States workers and workplaces in multiple ways including workplace violence events (WVEs). This analysis scanned online media sources to identify and describe the characteristics of WVEs related to COVID-19 occurring in the United States during the early phases of the pandemic. Method: Publicly available online media reports were searched for COVID-19-related WVEs during March 1- October 31, 2020. A list of 41 keywords was used to scan four search engines using Natural Language Processing (NLP). Authors manually reviewed media reports for inclusion using the study definition and to code variables of interest. Descriptive statistics were calculated across three types of violence: non-physical, physical, and events with both physical and non-physical violence. Results: The search of media reports found 400 WVEs related to COVID-19 during March 1- October 31, 2020. Of the WVEs, 27% (n&#160;=&#160;108) involved non-physical violence, 27% (n&#160;=&#160;109) physical violence, and 41% (n&#160;=&#160;164) both physical and non-physical violence. Nineteen WVEs could not be assigned to a specific type of violence (5%). Most occurred in retail and dining establishments (n&#160;=&#160;192, 48%; n&#160;=&#160;74, 19%, respectively). Most WVEs related to COVID-19 were perpetrated by a customer or client (n&#160;=&#160;298, 75%), but some were perpetrated by a worker (n&#160;=&#160;61, 15%). Most perpetrators were males (n&#160;=&#160;234, 59%) and acted alone (n&#160;=&#160;313, 79%). The majority of WVEs were related to mask disputes (n&#160;=&#160;286, 72%). In 22% of the WVEs, the perpetrator coughed or spit on a worker while threatening infection from SARS-CoV-2, the virus that causes COVID-19. Discussion: This analysis demonstrated that media scraping may be useful for workplace violence surveillance. The pandemic resulted in unique violent events, including those perpetrated by workers. Typical workplace violence prevention strategies may not be effective in reducing COVID-19-related violence. More research on workplace training for workers during public health crises is needed.

      4. COVID-19 vaccination perspectives and illnesses among law enforcement officers, firefighters, and other first responders in the US, January to September 2021
        Caban-Martinez AJ, Gaglani M, Olsho LE, Grant L, Schaefer-Solle N, Thompson MG, Burgess JL.
        JAMA Netw Open. 2022 Jul 1;5(7):e2222640.

      5. Epidemiologic investigation of two welder's anthrax cases caused by Bacillus cereus group bacteria: Occupational link established by environmental detection
        Dawson P, Salzer JS, Schrodt CA, Feldmann K, Kolton CB, Gee JE, Marston CK, Gulvik CA, Elrod MG, Villarma A, Traxler RM, Negrón ME, Hendricks KA, Moulton-Meissner H, Rose LJ, Byers P, Taylor K, Ware D, Balsamo GA, Sokol T, Barrett B, Payne E, Zaheer S, Jung GO, Long S, Quijano R, LeBouf L, O'Sullivan B, Swaney E, Antonini JM, Perio MA, Weiner Z, Bower WA, Hoffmaster AR.
        Pathogens. 2022 Jul 23;11(8).
        Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax.

      6. Emergency department personnel patient care-related COVID-19 risk
        Mohr NM, Krishnadasan A, Harland KK, Ten Eyck P, Mower WR, Schrading WA, Montoy JC, McDonald LC, Kutty PK, Hesse E, Santibanez S, Weissman DN, Slev P, Talan DA.
        PLoS One. 2022 ;17(7):e0271597.
        OBJECTIVES: Emergency department (ED) health care personnel (HCP) are at risk of exposure to SARS-CoV-2. The objective of this study was to determine the attributable risk of SARS-CoV-2 infection from providing ED care, describe personal protective equipment use, and identify modifiable ED risk factors. We hypothesized that providing ED patient care increases the probability of acquiring SARS-CoV-2 infection. METHODS: We conducted a multicenter prospective cohort study of 1,673 ED physicians, advanced practice providers (APPs), nurses, and nonclinical staff at 20 U.S. centers over 20 weeks (May to December 2020; before vaccine availability) to detect a four-percentage point increased SARS-CoV-2 incidence among HCP related to direct patient care. Participants provided monthly nasal and serology specimens and weekly exposure and procedure information. We used multivariable regression and recursive partitioning to identify risk factors. RESULTS: Over 29,825 person-weeks, 75 participants (4.5%) acquired SARS-CoV-2 infection (31 were asymptomatic). Physicians/APPs (aOR 1.07; 95% CI 0.56-2.03) did not have higher risk of becoming infected compared to nonclinical staff, but nurses had a marginally increased risk (aOR 1.91; 95% CI 0.99-3.68). Over 99% of participants used CDC-recommended personal protective equipment (PPE), but PPE lapses occurred in 22.1% of person-weeks and 32.1% of SARS-CoV-2-infected patient intubations. The following factors were associated with infection: household SARS-CoV-2 exposure; hospital and community SARS-CoV-2 burden; community exposure; and mask non-use in public. SARS-CoV-2 intubation was not associated with infection (attributable risk fraction 13.8%; 95% CI -2.0-38.2%), and nor were PPE lapses. CONCLUSIONS: Among unvaccinated U.S. ED HCP during the height of the pandemic, the risk of SARS-CoV-2 infection was similar in nonclinical staff and HCP engaged in direct patient care. Many identified risk factors were related to community exposures.

      7. High SARS-CoV-2 seroprevalence and rapid neutralizing antibody decline among agricultural workers in rural Guatemala, June 2020-March 2021
        Iwamoto C, Lesteberg KE, Lamb MM, Calvimontes DM, Guo K, Barrett BS, Mickens KL, Duca LM, Monzon J, Chard AN, Guzman G, Barrios E, Rojop N, Arias K, Gomez M, Paiz C, Bolanos GA, Edwards KM, Zielinski Gutierrez E, Azziz-Baumgartner E, Asturias EJ, Santiago ML, Beckham JD, Olson D.
        Vaccines (Basel). 2022 Jul 21;10(7).
        Essential agricultural workers work under occupational conditions that may increase the risk of SARS-CoV-2 exposure and transmission. Data from an agricultural worker cohort in Guatemala, and anti-SARS-CoV-2 nucleocapsid IgG (anti-N IgG) testing were used to estimate past infections and analyze risk factors associated with seropositivity at enrollment and association with SARS-CoV-2 infection. The stability of neutralizing antibody (NAb) responses were assessed in a subset of participants. The adjusted relative risk (aRR) for seroprevalence at enrollment was estimated accounting for correlations within worksites. At enrollment, 616 (46.2%) of 1334 (93.2%) participants had anti-N IgG results indicating prior SARS-CoV-2 infection. A cough ≤ 10 days prior to enrollment (aRR = 1.28, 95% CI: 1.13-1.46) and working as a packer (aRR = 2.00, 95% CI: 1.67-2.38) or packing manager within the plants (aRR = 1.82, 95% CI: 1.36-2.43) were associated with increased risk of seropositivity. COVID-19 incidence density among seronegative workers was 2.3/100 Person-Years (P-Y), higher than seropositive workers (0.4/100 P-Y). Most workers with follow-up NAb testing (65/77, 84%) exhibited a 95% average decrease in NAb titers in &lt;6 months. While participants seropositive at baseline were less likely to experience a symptomatic SARS-CoV-2 infection during follow-up, NAb titers rapidly waned, underscoring the need for multipronged COVID-19 prevention strategies in the workplace, including vaccination.

    • Parasitic Diseases
      1. Surveillance as a core intervention to strengthen malaria control programs in moderate to high transmission settings
        Fountain A, Ye Y, Roca-Feltrer A, Rowe AK, Camara A, Fofana A, Candrinho B, Hamainza B, Ndiop M, Steketee R, Thwing J.
        Am J Trop Med Hyg. 2022 Jun 6.
        New tools are needed for malaria control, and recent improvements in malaria surveillance have opened the possibility of transforming surveillance into a core intervention. Implementing this strategy can be challenging in moderate to high transmission settings. However, there is a wealth of practical experience among national malaria control programs and partners working to improve and use malaria surveillance data to guide programming. Granular and timely data are critical to understanding geographic heterogeneity, appropriately defining and targeting interventions packages, and enabling timely decision-making at the operational level. Resources to be targeted based on surveillance data include vector control, case management commodities, outbreak responses, quality improvement interventions, and human resources, including community health workers, as they contribute to a more refined granularity of the surveillance system. Effectively transforming malaria surveillance into a core intervention will require strong global and national leadership, empowerment of subnational and local leaders, collaboration among development partners, and global coordination. Ensuring that national health systems include community health work can contribute to a successful transformation. It will require a strong supply chain to ensure that all suspected cases can be diagnosed and data reporting tools including appropriate electronic devices to provide timely data. Regular data quality audits, decentralized implementation, supportive supervision, data-informed decision-making processes, and harnessing technology for data analysis and visualization are needed to improve the capacity for data-driven decision-making at all levels. Finally, resources must be available to respond programmatically to these decisions.

      2. Routine healthcare facility- and antenatal care-based malaria surveillance: Challenges and opportunities
        Gutman JR, Thwing J, Mwesigwa J, McElroy P, Robertson M.
        Am J Trop Med Hyg. 2022 Jun 6.
        Most monitoring and evaluation tools for measuring malaria burden, intervention coverage, and impact of interventions use periodic nationally representative cross-sectional household surveys. These provide advantages in terms of selecting a large, unbiased, population-based sample; however, they are infrequently conducted, are resource-intensive, and do not provide longitudinal data with sufficient granularity. Given the heterogeneity of malaria transmission within most endemic countries, systems with the capacity to provide more granular and frequent data would be more actionable by national malaria control programs and local implementing partners. There is increasing interest in using routine health facility data, usually from outpatient department visits, for monitoring malaria burden. Data from pregnant women attending antenatal care (ANC) could minimize bias related to fever care-seeking among outpatient department visits and provide more granular parasite prevalence data. Most pregnant women attend ANC at least once and are thus highly representative of the overall pregnant population. A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged < 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time. Additional data are needed to assess whether pregnant women are sufficiently representative of the overall population to yield valid malaria prevalence and intervention coverage estimates. Although use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable.

      3. Dracunculiasis eradication: End-stage challenges
        Hopkins DR, Weiss A, Torres-Velez FJ, Sapp SG, Ijaz K.
        Am J Trop Med Hyg. 2022 Jun 27.
        This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2021. Dracunculiasis (Guinea worm disease) has been eliminated from 17 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only Chad, Ethiopia, Mali, and South Sudan reported cases in humans in 2021. Chad, Ethiopia, and Mali also reported indigenous infections of animals, mostly domestic dogs, with Dracunculus medinensis. Insecurity and infections in animals are the main obstacles remaining to interrupting dracunculiasis transmission completely.

      4. Low Prevalence of deletions of the pfhrp2 and pfhrp3 genes in plasmodium falciparum parasites in Freetown, Sierra Leone in 2015
        McCaffery JN, Huber CS, Samai HM, Rogier E.
        Am J Trop Med Hyg. 2022 Jun 15;106(6):1667-1669.
        Sierra Leone relies heavily on histidine-rich protein 2-based diagnostics for malaria because of the high transmission of Plasmodium falciparum. During the 2015 recombinant vesicular stomatitis virus (VSV)-Zaire Ebola virus envelope glycoprotein (GP) vaccine trial, 77 participants with asymptomatic Plasmodium infection were enrolled, with all but four having P. falciparum malaria. Of the 73 participants with P. falciparum malaria, one infection (1 of 73, 1.4%; 95% CI, 0.03-7.4) showed P. falciparum with a pfhrp3 single deletion, and two P. falciparum infections (2 of 73, 2.7%; 95% CI, 0.03-9.6) showed pfhrp2/pfhrp3 dual deletions. This study shows evidence of pfhrp2- and pfhrp3-deleted parasites in Freetown, Sierra Leone. Additional studies for more precise estimates of prevalence are warranted.

      5. Etramp5 as a useful serological marker in children to assess the immediate effects of mass drug campaigns for malaria
        Druetz T, van den Hoogen L, Stresman G, Joseph V, Hamre KE, Fayette C, Monestime F, Presume J, Romilus I, Mondélus G, Elismé T, Cooper S, Impoinvil D, Ashton RA, Rogier E, Existe A, Boncy J, Chang MA, Lemoine JF, Drakeley C, Eisele TP.
        BMC Infect Dis. 2022 Jul 26;22(1):643.
        INTRODUCTION: Serological methods provide useful metrics to estimate age-specific period prevalence in settings of low malaria transmission; however, evidence on the use of seropositivity as an endpoint remains scarce in studies to evaluate combinations of malaria control measures, especially in children. This study aims to evaluate the immediate effects of a targeted mass drug administration campaign (tMDA) in Haiti by using serological markers. METHODS: The tMDA was implemented in September-October 2018 using sulfadoxine-pyrimethamine and single low-dose primaquine. A natural quasi-experimental study was designed, using a pretest and posttest in a cohort of 754 randomly selected school children, among which 23% reported having received tMDA. Five antigens were selected as outcomes (MSP1-19, AMA-1, Etramp5 antigen 1, HSP40, and GLURP-R0). Posttest was conducted 2-6 weeks after the intervention. RESULTS: At baseline, there was no statistical difference in seroprevalence between the groups of children that were or were not exposed during the posttest. A lower seroprevalence was observed for markers informative of recent exposure (Etramp5 antigen 1, HSP40, and GLURP-R0). Exposure to tMDA was significantly associated with a 50% reduction in the odds of seropositivity for Etramp5 antigen 1 and a 21% reduction in the odds of seropositivity for MSP119. CONCLUSION: Serological markers can be used to evaluate the effects of interventions against malaria on the risk of infection in settings of low transmission. Antibody responses against Etramp5 antigen 1 in Haitian children were reduced in the 2-6 weeks following a tMDA campaign, confirming its usefulness as a short-term marker in child populations.

      6. Evaluation of the performance of Ortho T. cruzi ELISA test system for the detection of antibodies to trypanosoma cruzi
        Rivera HN, McAuliffe I, Aderohunmu T, Wiegand RE, Montgomery SP, Bradbury RS, Handali S.
        J Clin Microbiol. 2022 Jul 12:e0013422.
        The serologic diagnosis of chronic Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is challenging and lacks a gold-standard assay. To overcome the problem, CDC uses an algorithm that uses two tests on different platforms and applies a third test as a tiebreaker. The Ortho T. cruzi ELISA Test System from Ortho Diagnostics was cleared by FDA for clinical diagnosis usage. We evaluated this test against the CDC algorithm for chronic Chagas disease. We tested several sets of serum specimens: 104 specimens tested positive for T. cruzi specific antibody and 283 (including 30 specimens positive for antibody to Leishmania spp.) tested negative based on the current CDC chronic T. cruzi infection diagnostic testing algorithm. Concordance of the Ortho T. cruzi ELISA Test System with the CDC algorithm result was 90% (95% CI 87 to 93%) overall and 92% (95% CI 89 to 95%) when excluding Leishmania spp. antibody positive specimens. The cross-reactivity of the Ortho T. cruzi ELISA Test System was 37% to Leishmania spp. serologically positive specimens, 1% to specimens from patients diagnosed with other parasitic infections, and 0% against specimens from a US noninfected population. In conclusion, the Ortho T. cruzi ELISA Test System compares well against the CDC diagnostic algorithm for chronic Chagas disease. The availability of this FDA-cleared assay will improve the chronic Chagas disease diagnosis.

      7. An outbreak of malaria caused by increase in malaria breeding sites in swamps
        Kabwama SN, Kwesiga B, Bulage L, Kadobera D, Ario AR, Harris JR.
        Pan Afr Med J. 2022 ;41.
        On 10th June 2019, routine analysis of malaria surveillance data at the National Malaria Control Division, Ministry of Health in Uganda revealed that there was an unusual increase in the number of malaria cases reported in the Oyam District. On 11th June 2019, the District Health Officer in Oyam District convened a meeting with the District Health Team (DHT) in which the District Biostatistician confirmed that the number of malaria cases had indeed exceeded the upper limit, starting in epidemic week 24 (approximately the week of June 10). The District Health Officer issued a formal request to the Ministry of Health for assistance in dealing with the malaria outbreak in Oyam. Two field epidemiology residents were assigned to work with the District Health Team to investigate the outbreak. The residents followed the steps in conducting vector borne disease outbreak investigations including preparation for field work, establishment of the existence of an outbreak by analyzing surveillance data, descriptive data analysis, hypothesis generation, conducting environmental and entomological assessments, conducting analytic studies with a focus on the utility of retrospective cohort studies as well as reporting findings. This case study teaches trainees in Field Epidemiology and Laboratory Training Programs, public health students, public health workers who are interested or who may participate in vector borne disease outbreak investigation and response. © Steven Ndugwa et al.

      8. Malaria outbreak in Mbale: it´s the pits! a case study
        Kadobera D, Bahizi G, Bulage L, Kwesiga B, Kabwama SN, Ario AR, Harris JR.
        Pan Afr Med J. 2022 ;41.
        Malaria is a leading cause of morbidity and mortality in Uganda. In June 2019, the Uganda Ministry of Health through routine surveillance data analysis was notified of an increase in malaria cases in Bumbobi and Nyondo Sub-counties, Mbale District, which exceeded the action thresholds. We investigated to assess outbreak magnitude, identify transmission risk factors, and recommend evidence-based control measures. We defined a confirmed case as a positive malaria result using malaria Rapid Diagnostic Test or microscopy from 1 Jan 2019 to 30 Jun 2019 in a resident or visitor of Bumbobi or Nyondo Sub-county, Mbale District. We reviewed medical records to develop a line list for descriptive epidemiology. In a case-control study, we compared exposures between 150 case-persons and 150 age-and village-matched asymptomatic controls. We conducted environmental and entomological assessments on vector dynamics and behavior. We identified 7,891 case-persons (attack rate [AR]=26%). Females (AR=36%) were more affected than males (AR=25%). The 5-18 year age group (AR=26%) was most affected. The epidemic curve showed steady increase in malaria cases from March following intermittent rainfall from January, with short spells of no rainfall up to June. In the matched pair case-control analysis, 95% (143/150) of case-patients and 49% (73/150) of controls had soil erosion control pits near their homes that held stagnant water for several days following rainfall (AOR=18, 95%CI=7-50); Active breeding sites were found near and within homesteads with Anopheles gambiaeas the predominant vector. Increased vector breeding sites due to erosion control pits sustained by the intermittent rainfall caused this outbreak. We recommended draining of pits immediately after the rains and increasing coverage for bed-nets. © Daniel Kadobera et al.

      9. Evidence of likely autochthonous Chagas disease in the southwestern United States: A case series of Trypanosoma cruzi seropositive blood donors
        Lynn MK, Dye-Braumuller KC, Beatty NL, Dorn PL, Klotz SA, Stramer SL, Townsend RL, Kamel H, Vannoy JM, Sadler P, Montgomery SP, Rivera HN, Nolan MS.
        Transfusion. 2022 Jul 27.
        BACKGROUND: Chagas disease is a parasitic infection that can insidiously cause non-ischemic cardiomyopathy. Given the largely silent nature of this progressive disease, asymptomatic blood donors pose potential blood transfusion risk. Blood donation screening has become an unintentional form of Chagas disease surveillance, with thousands of new cases identified since national surveillance was initiated in 2007. STUDY DESIGN AND METHODS: We recruited T. cruzi-positive blood donors identified from California and Arizona blood centers for confirmatory blood screening and assessment of lifetime infection risk. RESULTS: Among eight suspected cases, we identified four confirmed US autochthonous infections. The current manuscript details the transmission sources, healthcare-seeking behaviors post-blood donation resulting, and clinical course of disease among persons without any history of travel to endemic Latin American countries. DISCUSSION: This manuscript presents four additional US-acquired Chagas disease cases and identifies an opportunity for blood centers to assist in confronting barriers surrounding Chagas disease in the US.

    • Substance Use and Abuse
      1. Estimating weekly national opioid overdose deaths in near real time using multiple proxy data sources
        Sumner SA, Bowen D, Holland K, Zwald ML, Vivolo-Kantor A, Guy GP, Heuett WJ, Pressley DP, Jones CM.
        JAMA Netw Open. 2022 Jul 1;5(7):e2223033.
        IMPORTANCE: Opioid overdose is a leading public health problem in the United States; however, national data on overdose deaths are delayed by several months or more. OBJECTIVES: To build and validate a statistical model for estimating national opioid overdose deaths in near real time. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, signals from 5 overdose-related, proxy data sources encompassing health, law enforcement, and online data from 2014 to 2019 in the US were combined using a LASSO (least absolute shrinkage and selection operator) regression model, and weekly predictions of opioid overdose deaths were made for 2018 and 2019 to validate model performance. Results were also compared with those from a baseline SARIMA (seasonal autoregressive integrated moving average) model, one of the most used approaches to forecasting injury mortality. EXPOSURES: Time series data from 2014 to 2019 on emergency department visits for opioid overdose from the National Syndromic Surveillance Program, data on the volume of heroin and synthetic opioids circulating in illicit markets via the National Forensic Laboratory Information System, data on the search volume for heroin and synthetic opioids on Google, and data on post volume on heroin and synthetic opioids on Twitter and Reddit were used to train and validate prediction models of opioid overdose deaths. MAIN OUTCOMES AND MEASURES: Model-based predictions of weekly opioid overdose deaths in the United States were made for 2018 and 2019 and compared with actual observed opioid overdose deaths from the National Vital Statistics System. RESULTS: Statistical models using the 5 real-time proxy data sources estimated the national opioid overdose death rate for 2018 and 2019 with an error of 1.01% and -1.05%, respectively. When considering the accuracy of weekly predictions, the machine learning-based approach possessed a mean error in its weekly estimates (root mean squared error) of 60.3 overdose deaths for 2018 (compared with 310.2 overdose deaths for the SARIMA model) and 67.2 overdose deaths for 2019 (compared with 83.3 overdose deaths for the SARIMA model). CONCLUSIONS AND RELEVANCE: Results of this serial cross-sectional study suggest that proxy administrative data sources can be used to estimate national opioid overdose mortality trends to provide a more timely understanding of this public health problem.

      2. Vital signs: Drug overdose deaths, by selected sociodemographic and social determinants of health characteristics - 25 states and the District Of Columbia, 2019-2020
        Kariisa M, Davis NL, Kumar S, Seth P, Mattson CL, Chowdhury F, Jones CM.
        MMWR Morb Mortal Wkly Rep. 2022 Jul 22;71(29):940-947.
        INTRODUCTION: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths. METHODS: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability). RESULTS: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed.

      3. Hepatitis C virus transmission cluster among injection drug users in Pakistan
        Sahibzada KI, Ganova-Raeva L, Dimitrova Z, Ramachandran S, Lin Y, Longmire G, Arthur L, Xia GL, Khudyakov Y, Khan I, Sadaf S.
        PLoS One. 2022 ;17(7):e0270910.
        Hepatitis C virus (HCV) infections are public health problem across the globe, particularly in developing countries. Pakistan has the second highest prevalence of HCV infection worldwide. Limited data exist from Pakistan about persons who inject drugs (PWID) and are at significant risk of exposure to HCV infection and transmission. Serum specimens (n = 110) collected from PWID residing in four provinces were tested for molecular markers of HCV infection. Next generation sequencing (NGS) of the hypervariable region (HVR1) of HCV and Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to determine HCV genotype, genetic heterogeneity, and construct transmission networks. Among tested specimens, 47.3% were found anti-HCV positive and 34.6% were HCV RNA-positive and belonged to four genotypes, with 3a most prevalent followed by 1a, 1b and 4a. Variants sampled from five cases formed phylogenetic cluster and a transmission network. One case harbored infection with two different genotypes. High prevalence of infections and presence of various genotypes indicate frequent introduction and transmission of HCV among PWID in Pakistan. Identification of a transmission cluster across three provinces, involving 20% of all cases, suggests the existence of a countrywide transmission network among PWIDs. Understanding the structure of this network should assist in devising effective public health strategies to eliminate HCV infection in Pakistan.

    • Zoonotic and Vectorborne Diseases
      1. The Amazonian Tropical Bites Research Initiative, a hope for resolving zoonotic neglected tropical diseases in the One Health era
        Taylor E, Aguilar-Ancori EG, Banyard AC, Abel I, Mantini-Briggs C, Briggs CL, Carrillo C, Gavidia CM, Castillo-Neyra R, Parola AD, Villena FE, Prada JM, Petersen BW, Falcon Perez N, Cabezas Sanchez C, Sihuincha M, Streicker DG, Maguina Vargas C, Navarro Vela AM, Vigilato MA, Wen Fan H, Willoughby R, Horton DL, Recuenco SE.
        Int Health. 2022 Jul 27.
        BACKGROUND: Neglected tropical diseases (NTDs) disproportionately affect populations living in resource-limited settings. In the Amazon basin, substantial numbers of NTDs are zoonotic, transmitted by vertebrate (dogs, bats, snakes) and invertebrate species (sand flies and triatomine insects). However, no dedicated consortia exist to find commonalities in the risk factors for or mitigations against bite-associated NTDs such as rabies, snake envenoming, Chagas disease and leishmaniasis in the region. The rapid expansion of COVID-19 has further reduced resources for NTDs, exacerbated health inequality and reiterated the need to raise awareness of NTDs related to bites. METHODS: The nine countries that make up the Amazon basin have been considered (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Surinam and Venezuela) in the formation of a new network. RESULTS: The Amazonian Tropical Bites Research Initiative (ATBRI) has been created, with the aim of creating transdisciplinary solutions to the problem of animal bites leading to disease in Amazonian communities. The ATBRI seeks to unify the currently disjointed approach to the control of bite-related neglected zoonoses across Latin America. CONCLUSIONS: The coordination of different sectors and inclusion of all stakeholders will advance this field and generate evidence for policy-making, promoting governance and linkage across a One Health arena.

      2. Fight the bite: implementation of mosquito-based curriculum in elementary, middle, and high schools in Florida
        Parker-Crockett C, Rampold SD, Galindo S, Bunch JC, Yoder H, Thoron A, Andenoro A, Connelly CR, Lucky A, Telg R.
        J Agric Educ. 2022 ;63(2):37-51.
        Mosquitoes are both a nuisance and public health threat. In recent decades, outbreaks of dengue, chikungunya, and Zika in Florida have raised awareness of the importance of domestic and peri-domestic container mosquitoes, Aedes aegypti and Aedes albopictus. The synanthropic nature of these species, coupled with their preference for human bloodmeals, makes them a concern of and target for mosquito control. However, mosquito control programs (MCPs) often struggle to sustainably manage these mosquitoes because of the cryptic and abundant nature of their larval habitats, and negative public opinion towards MCPs and the use of insecticides. Fortunately, mosquito control can be improved by the actions of homeowners and residents as they have regular access to their own property and containers. School-based education programs can provide a means to community-wide education regarding mosquito control. We developed and delivered a mosquito education program to elementary, middle, and high school students. Knowledge of mosquitoes significantly improved in participating elementary and middle/ high school students. This knowledge was partially retained according to a follow-up test that was administered. Additionally, attitudes towards mosquito control and at-home control methods significantly improved following the instruction. The improvements in knowledge and attitudes observed in students suggest they can and should be targeted for mosquito education campaigns by mosquito control programs and educators.

      3. Adaptation to a multiplex bead assay and seroprevalence to Rift Valley Fever N protein: Nampula Province, Mozambique, 2013-2014
        Rogier E, Plucinski M, Candrinho B, Moss DM, Gibbons A, Colborn J, Higgins J, Chambe G, Muchanga J, Muguande O, Matsinhe G, Mathe G, Doyle T, Zulliger R, Saifodine A, Montgomery JM, Klena JD, Priest JW.
        J Virol. 2022 Jul 27:e0067222.
        Rift Valley fever virus (RVFV) is endemic in sub-Saharan Africa (SSA), with outbreaks reported in the Arabian Peninsula and throughout SSA. The natural reservoir for RVFV are ruminants, with livestock populations exceeding 50% exposure rates in some areas of SSA. Transmission to humans can occur through exposure to infected livestock products or multiple species of mosquito vectors. In 2013 and 2014, cross-sectional surveys occurred in two districts of Nacala-a-Velha and Mecubúri in northern Mozambique, and participants provided blood samples for later serological assays. IgG against the N protein of RVFV was detected through multiplex bead assay (MBA). Of the 2,278 persons enrolled between the two surveys and study sites, 181 (7.9%, 95% confidence interval (CI): 6.9%-9.1%) were found to be IgG seropositive with increasing seroprevalence with older age and significantly higher seroprevalence in Nacala-a-Velha (10.5%, 8.8%-12.5%) versus Mecubúri (5.7%, 4.5%-7.1%). Seroprevalence estimates were not significantly different between the 2013 and 2014 surveys. Significant spatial clustering of IgG positive persons were consistent among surveys and within the two districts, pointing toward the consistency of serology data for making population-level assumptions regarding RVFV seroprevalence. A subset of persons (n = 539) provided samples for both the 2013 and 2014 surveys, and a low percentage (0.81%) of these were found to seroconvert between these two surveys. Including the RVFV N protein in an MBA antigen panel could assist elucidate RVFV exposure in SSA. IMPORTANCE Due to sporadic transmission, human contact with Rift Valley Fever Virus (RVFV) is difficult to ascertain at a population level. Detection of antibodies against RVFV antigens assist in estimating exposure as antibodies remain in the host long after the virus has been cleared. In this study, we show that antibodies against RVFV N protein can be detected from dried blood spot (DBS) samples being assayed by multiplex bead assay. DBS from two districts in northern Mozambique were tested for IgG against the N protein, and 7.9% of all enrolled persons were seropositive. Older persons, males, and persons residing closer to the coast had higher RVFV N protein seroprevalence. Spatial clustering of IgG positive persons was noted in both districts. These results show low exposure rates to RVFV in these two northern districts in Mozambique, and the ability to perform serology for the RVFV N protein from dried blood samples.

      4. Arbovirus risk perception as a predictor of mosquito-bite preventive behaviors in Ponce, Puerto Rico
        Dussault JM, Paz-Bailey G, Sánchez-González L, Adams LE, Rodríguez DM, Ryff KR, Major CG, Lorenzi O, Rivera-Amill V.
        PLoS Negl Trop Dis. 2022 Jul 26;16(7):e0010653.
        Mosquito-borne arboviruses are an important cause of morbidity and mortality in the Caribbean. In Puerto Rico, chikungunya, dengue, and Zika viruses have each caused large outbreaks during 2010-2022. To date, the majority of control measures to prevent these diseases focus on mosquito control and many require community participation. In 2018, the U.S. Centers for Disease Control and Prevention launched the COPA project, a community-based cohort study in Ponce, Puerto Rico, to measure the impact of novel vector control interventions in reducing arboviral infections. Randomly selected households from 38 designated cluster areas were offered participation, and baseline data were collected from 2,353 households between May 2018 and May 2019. Household-level responses were provided by one representative per home. Cross-sectional analyses of baseline data were conducted to estimate 1) the association between arboviral risk perception and annual household expenditure on mosquito control, and 2) the association between arboviral risk perception and engagement in ≥3 household-level risk reduction behaviors. In this study, 27% of household representatives believed their household was at high risk of arboviruses and 36% of households engaged in at least three of the six household-level preventive behaviors. Households where the representative perceived their household at high risk spent an average of $35.9 (95% confidence interval: $23.7, $48.1) more annually on mosquito bite prevention compared to households where the representative perceived no risk. The probability of engaging in ≥3 household-level mosquito-preventive behaviors was 10.2 percentage points greater (7.2, 13.0) in households where the representatives perceived high risk compared to those in which the representatives perceived no risk. Paired with other research, these results support investment in community-based participatory approaches to mosquito control and providing accessible information for communities to accurately interpret their risk.

      5. Vaccine preventable zoonotic diseases: Challenges and opportunities for public health progress
        Carpenter A, Waltenburg MA, Hall A, Kile J, Killerby M, Knust B, Negron M, Nichols M, Wallace RM, Behravesh CB, McQuiston JH.
        Vaccines (Basel). 2022 Jun 22;10(7).
        Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and implement vaccine interventions to reduce zoonotic disease impacts are often limited to the veterinary and agricultural sectors and do not reflect the shared burden of disease. Multisectoral collaboration, including co-development opportunities for human and animal vaccines, expanding vaccine use to include animal reservoirs such as wildlife, and strategically using vaccines to interrupt complex transmission cycles is needed. Addressing zoonoses requires a multi-faceted One Health approach, wherein vaccinating people and animals plays a critical role.

      6. Colorado tick fever virus in the far west: Forgotten, but not gone
        Padgett KA, Kjemtrup A, Novak M, Velez JO, Panella N.
        Vector Borne Zoonotic Dis. 2022 Jul 25.
        In the past few decades, reported human cases of Colorado tick fever in the western United States have decreased dramatically. The goal of this study was to conduct surveillance for Colorado tick fever virus (CTFV) in Dermacentor ticks in recreational sites in Colorado, Wyoming, and California to determine whether the virus is still present in Dermacentor ticks from these states. Surveillance focused on regions where surveys had been conducted in the 1950s, 1960s, and 1970s. Adult Rocky Mountain wood ticks (Dermacentor andersoni), Pacific Coast ticks (Dermacentor occidentalis), and winter ticks (Dermacentor albipictus) were tested by PCR. A subset of PCR-positive D. andersoni ticks (n = 7) were cultured in Vero cells. CTFV-positive Rocky Mountain wood ticks were found in all states: Colorado (58% prevalence), Wyoming (21%), and California (4%). Although no winter ticks tested positive, Pacific Coast ticks tested positive in one county (Siskiyou County, 15% prevalence) and were positive only in a location that also maintained Rocky Mountain wood ticks and golden mantled ground squirrels, a known CTFV host. In summary, CTFV is prevalent in D. andersoni and D. occidentalis in regions where they are sympatric in California and in D. andersoni in Colorado and Wyoming. Although the number of human CTFV cases has declined dramatically, this decrease in reported disease does not appear to be due to the disappearance or even the decline in prevalence of this virus in ticks in historically endemic regions of the country.

      7. Genetic adaptation by dengue virus serotype 2 to enhance infection of Aedes aegypti mosquito midguts
        Erb SM, Butrapet S, Roehrig JT, Huang CY, Blair CD.
        Viruses. 2022 Jul 19;14(7).
        Dengue viruses (DENVs), serotypes 1-4, are arthropod-borne viruses transmitted to humans by mosquitoes, primarily Aedes aegypti. The transmission cycle begins when Ae. aegypti ingest blood from a viremic human and the virus infects midgut epithelial cells. In studying viruses derived from the DENV2 infectious clone 30P-NBX, we found that when the virus was delivered to female Ae. aegypti in an infectious blood meal, the midgut infection rate (MIR) was very low. To determine if adaptive mutations in the DENV2 envelope (E) glycoprotein could be induced to increase the MIR, we serially passed 30P-NBX in Ae. aegypti midguts. After four passages, a single, non-conservative mutation in E protein domain II (DII) nucleotide position 1300 became dominant, resulting in replacement of positively-charged amino acid lysine (K) at position 122 with negatively-charged glutamic acid (E; K122E) and a significantly-enhanced MIR. Site directed mutagenesis experiments showed that reducing the positive charge of this surface-exposed region of the E protein DII correlated with improved Ae. aegypti midgut infection.

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

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