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Issue 12, March 22, 2022

CDC Science Clips: Volume 14, Issue 12, March 22, 2022

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

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. GdhR is a transcriptional repressor of the virulence factor gene lctP, which encodes a unique l-lactate permease that has been linked to pathogenesis of Neisseria gonorrhoeae, and loss of gdhR can confer increased fitness of gonococci in a female mouse model of lower genital tract infection. In this work, we identified a single nucleotide polymorphism (SNP) in gdhR, which is often present in both recent and historical gonococcal clinical strains and results in a proline (P)-to-serine (S) change at amino acid position 6 (P6S) of GdhR. This mutation (gdhR6) was found to reduce GdhR transcriptional repression at lctP in gonococcal strains containing the mutant protein compared to wild-type GdhR. By using purified recombinant proteins and in vitro DNA-binding and cross-linking experiments, we found that gdhR6 impairs the DNA-binding activity of GdhR at lctP without an apparent effect on protein oligomerization. By analyzing a panel of U.S. (from 2017 to 2018) and Danish (1928 to 2013) clinical isolates, we observed a statistical association between gdhR6 and the previously described adenine deletion in the promoter of mtrR (mtrR-P A-del), encoding the repressor (MtrR) of the mtrCDE operon that encodes the MtrCDE multidrug efflux pump that can export antibiotics, host antimicrobials, and biocides. The frequent association of gdhR6 with the mtrR promoter mutation in these clinical isolates suggests that it has persisted in this genetic background to enhance lctP expression, thereby promoting virulence. IMPORTANCE We report the frequent appearance of a novel SNP in the gdhR gene (gdhR6) possessed by Neisseria gonorrhoeae. The resulting amino acid change in the GdhR protein resulted in enhanced expression of a virulence gene (lctP) that has been suggested to promote gonococcal survival during infection. The mutant GdhR protein expressed by gdhR6 had a reduced ability to bind to its target DNA sequence upstream of lctP. Interestingly, gdhR6 was found in clinical gonococcal strains isolated in the United States and Denmark at a high frequency and was frequently associated with a mutation in the promoter of the gene encoding a repressor (MtrR) of both the mtrCDE antimicrobial efflux pump operon and gdhR. Given this frequent association and the known impact of these regulatory mutations, we propose that virulence and antibiotic resistance properties are often phenotypically linked in contemporary gonococcal strains.

    • Chronic Diseases and Conditions
      1. How do we jump-start self-measured blood pressure monitoring in the United States? Addressing barriers beyond the published literatureexternal icon
        Wall HK, Wright JS, Jackson SL, Daussat L, Ramkissoon N, Schieb LJ, Stolp H, Tong X, Loustalot F.
        Am J Hypertens. 2022 Mar 8;35(3):244-255.
        Hypertension is highly prevalent in the United States, and many persons with hypertension do not have controlled blood pressure. Self-measured blood pressure monitoring (SMBP), when combined with clinical support, is an evidence-based strategy for lowering blood pressure and improving control in persons with hypertension. For years, there has been support for widespread implementation of SMBP by national organizations and the federal government, and SMBP was highlighted as a primary intervention in the 2020 Surgeon General's Call to Action to Control Hypertension, yet optimal SMBP use remains low. There are well-known patient and clinician barriers to optimal SMBP documented in the literature. We explore additional high-level barriers that have been encountered, as broad policy and systems-level changes have been attempted, and offer potential solutions. Collective efforts could modernize data transfer and processing, improve broadband access, expand device coverage and increase affordability, integrate SMBP into routine care and reimbursement practices, and strengthen patient engagement, trust, and access.

      2. BACKGROUND: Longer intervals between prostate-specific antigen (PSA) tests for routine prostate cancer screening can reduce the harms while maintaining the benefits of screening. Limited information has been published on PSA screening frequency. The purpose of this report is to describe the number of PSA tests in the last 5 years reported by men in the United States. METHODS: Using data from National Health Interview Survey Cancer Control Supplements in 2010, 2015, and 2018, the number of PSA tests in the last 5 years reported by men ≥40 years was categorized as 4 to 5 PSA tests, 1 to 3 PSA tests, and no PSA tests. Logistic regression was used to calculate model-adjusted prevalence risk ratios (aPRs) for the number of PSA tests in the last 5 years, adjusting for age, racial-ethnic group, education, marital status, and health insurance. RESULTS: The proportion of men aged ≥70 years who reported 4 to 5 PSA tests in the last 5 years decreased from 37.2% in 2010 to 31.1% in 2018, while the proportion reporting 1 to 3 PSA tests increased from 25.5% to 31.9%. In 2018, aPRs for 4 to 5 PSA tests vs. 1 to 3 PSA tests in the last 5 years were significantly higher among men aged 70 to 79 years than among men aged 55 to 69 years. CONCLUSIONS: Men aged ≥70 years reported a small shift to less intense PSA testing between 2010 and 2018, but PSA testing intensity remained higher in men aged ≥70 years than in men aged 55 to 69 years.

    • Communicable Diseases

      1. Effects of buprenorphine treatment on influenza pathogenesis in the ferret (Mustela putorius furo)external icon
        Mrotz VJ, Nestor KM, Maines TR, Powell N, Belser JA.
        Comp Med. 2022 Feb 1;72(1):22-29.
        Ferrets are the gold-standard model for influenza A virus (IAV) research due to their natural susceptibility to human and zoonotic IAV, comparable respiratory anatomy and physiology to humans, and development of clinical signs similar to those seen in infected people. Because the presence and progression of clinical signs can be useful in infectious disease research, uncertainty in how analgesics alter research outcomes or compromise characteristics of disease progression have outweighed the concern regarding animal discomfort from these symptoms. Nonetheless, the principles of animal research require consideration of refinements for this important model for IAV research. Opioids offer a possible refinement option that would not directly affect the inflammatory cascade involved in IAV infection. Mirroring pathogenicity studies that use ferrets, 12 ferrets were inoculated intranasally with the A(H3N2) IAV A/Panama/2007/1999 and divided into 3 treatment groups ( n = 4 each), of which 2 groups received buprenorphine treatments on different schedules and the third received a saline control. The duration and location of viral replication, lymphohematopoietic changes, and clinical signs were comparable across all groups at all time points. High quantities of infectious virus in nasal wash specimens were detected in ferrets from all groups through day 5 after inoculation, and peak viral titers from the upper respiratory tract did not differ between ferrets receiving buprenorphine treatments on either schedule. Compared with the saline group, ferrets receiving buprenorphine exhibited transient weight loss and pyrexia, but all groups ultimately achieved similar peaks in both of these measurements. Collectively, these findings support the continued evaluation of buprenorphine as a refinement for IAV-challenged ferrets.

      2. Genomic insights on variation underlying capsule expression in meningococcal carriage isolates from university students, United States, 2015-2016external icon
        Whaley MJ, Vuong JT, Topaz N, Chang HY, Thomas JD, Jenkins LT, Hu F, Schmink S, Steward-Clark E, Mathis M, Rodriguez-Rivera LD, Retchless AC, Joseph SJ, Chen A, Acosta AM, McNamara L, Soeters HM, Mbaeyi S, Marjuki H, Wang X.
        Front Microbiol. 2022 ;13:815044.
        In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen.

      3. Brief report: No differences between lopinavir/ritonavir and nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy on clearance of plasmodium falciparum subclinical parasitemia in adults living with HIV starting treatment (A5297)external icon
        Shaffer D, Kumwenda J, Chen H, Akelo V, Angira F, Kosgei J, Tonui R, Ssali F, McKhann A, Hogg E, Stewart VA, Murphy SC, Coombs R, Schooley R.
        J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):178-182.
        BACKGROUND: HIV protease inhibitors anti-Plasmodium falciparum activity in adults remains uncertain. METHODS: Adults with HIV CD4+ counts >200 cells/mm3 starting antiretroviral therapy (ART) with P. falciparum subclinical parasitemia (Pf SCP) were randomized 1:1 to (step 1) protease inhibitor lopinavir/ritonavir (LPV/r)-based (arm A) or nonnucleoside reverse transcriptase inhibitor (nNRTI)-based ART (arm B) for 15 days. In step 2, participants received nNRTI-based ART and trimethoprim/sulfamethoxazole prophylaxis for 15 days. P. falciparum SCP clearance was measured by polymerase chain reaction. The Fisher exact test [95% exact confidence interval (CI)] was used to compare proportions of P. falciparum SCP clearance (<10 parasites/μL on 3 occasions within 24 hours) between LPV/r and nNRTI arms at day 15. The Kaplan-Meier method and log-rank test were used to compare time-to-clearance. RESULTS: Fifty-two adults from Kenya, Malawi, and Uganda with a median age = 31 (Q1, Q3: 24-39) years, 33% women, with baseline median CD4+ counts of 324 (259-404) cells/mm3, median HIV-1 RNA viremia of 5.18 log10 copies/mL (4.60-5.71), and median estimated P. falciparum density of 454 parasites/μL (83-2219) enrolled in the study. Forty-nine (94%) participants completed the study. At day 15, there was no statistically significant difference in the proportions of P. falciparum SCP clearance between the LPV/r (23.1% clearance; 6 of the 26) and nNRTI (26.9% clearance; 7 of the 26) arms [between-arm difference 3.9% (95% CI, -21.1% to 28.4%; P = 1.00)]. No significant difference in time-to-clearance was observed between the arms (P = 0.80). CONCLUSIONS: In a small randomized study of adults starting ART with P. falciparum SCP, no statistically significant differences were seen between LPV/r- and nNRTI-based ART in P. falciparum SCP clearance after 15 days of treatment.

      4. Correctional-facility-outbreak-associated COVID-19 cases among asymptomatic persons identified through universal testing: Vermont, 2020external icon
        Pringle JC, Fritch WM, Boire Y, Meddaugh P, Prue T, Dunsmore B, Fox H, Reid H, Robinson ME, Kwit N.
        J Correct Health Care. 2022 Mar 9.
        On April 6, 2020, a confirmed COVID-19 case in a correctional facility employee (Staff A) was reported to the Vermont Department of Health (VDH). Staff A worked in the facility while symptomatic, without reporting symptoms, for 10 days. VDH and the facility conducted two facility-wide testing events, implemented symptom monitoring, and initiated contact tracing. All 197 incarcerated persons and 115 (71%) staff were tested for SARS-CoV-2; 45 (23%) incarcerated persons and 17 (10%) staff had positive results (confirmed case), of whom 37 (82%) incarcerated persons and 1 (6%) staff had asymptomatic infections. Case detection enabled isolation of incarcerated persons and staff, work exclusion of staff with COVID-19, and quarantine of staff and incarcerated persons who had close contact with persons with COVID-19. Broad-based SARS-CoV-2 testing identified more cases than symptom monitoring.

      5. HIV surveillance and research for migrant populations: Protocol integrating respondent-driven sampling, case finding, and medicolegal services for Venezuelans living in Colombiaexternal icon
        Wirtz AL, Page KR, Stevenson M, Guillén JR, Ortíz J, López JJ, Ramírez JF, Quijano C, Vela A, Moreno Y, Rigual F, Case J, Hakim AJ, Hladik W, Spiegel PB.
        JMIR Res Protoc. 2022 Mar 8;11(3):e36026.
        BACKGROUND: Epidemiologic research among migrant populations is limited by logistical, methodological, and ethical challenges, but it is necessary for informing public health and humanitarian programming. OBJECTIVE: We describe a methodology to estimate HIV prevalence among Venezuelan migrants in Colombia. METHODS: Respondent-driven sampling, a nonprobability sampling method, was selected for attributes of reaching highly networked populations without sampling frames and analytic methods that permit estimation of population parameters. Respondent-driven sampling was modified to permit electronic referral of peers via SMS text messaging and WhatsApp. Participants complete sociobehavioral surveys and rapid HIV and syphilis screening tests with confirmatory testing. HIV treatment is not available for migrants who have entered Colombia through irregular pathways; thus, medicolegal services integrated into posttest counseling provide staff lawyers and legal assistance to participants diagnosed with HIV or syphilis for sustained access to treatment through the national health system. Case finding is integrated into respondent-driven sampling to allow partner referral. This study is implemented by a local community-based organization providing HIV support services and related legal services for Venezuelans in Colombia. RESULTS: Data collection was launched in 4 cities in July and August 2021. As of November 2021, 3105 of the target 6100 participants were enrolled, with enrollment expected to end by February/March 2022. CONCLUSIONS: Tailored methods that combine community-led efforts with innovations in sampling and linkage to care can aid in advancing health research for migrant and displaced populations. Worldwide trends in displacement and migration underscore the value of improved methods for translation to humanitarian and public health programming. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36026.

      6. SARS-CoV-2 B.1.1.529 (Omicron) variant transmission within households - four U.S. jurisdictions, November 2021-February 2022external icon
        Baker JM, Nakayama JY, O'Hegarty M, McGowan A, Teran RA, Bart SM, Mosack K, Roberts N, Campos B, Paegle A, McGee J, Herrera R, English K, Barrios C, Davis A, Roloff C, Sosa LE, Brockmeyer J, Page L, Bauer A, Weiner JJ, Khubbar M, Bhattacharyya S, Kirking HL, Tate JE.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 4;71(9):341-346.
        The B.1.1.529 (Omicron) variant, first detected in November 2021, was responsible for a surge in U.S. infections with SARS-CoV-2, the virus that causes COVID-19, during December 2021-January 2022 (1). To investigate the effectiveness of prevention strategies in household settings, CDC partnered with four U.S. jurisdictions to describe Omicron household transmission during November 2021-February 2022. Persons with sequence-confirmed Omicron infection and their household contacts were interviewed. Omicron transmission occurred in 124 (67.8%) of 183 households. Among 431 household contacts, 227 were classified as having a case of COVID-19 (attack rate [AR] = 52.7%).(†) The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively. The AR was lower among household contacts of index patients who isolated (41.2%, 99 of 240) compared with those of index patients who did not isolate (67.5%, 112 of 166) (p-value <0.01). Similarly, the AR was lower among household contacts of index patients who ever wore a mask at home during their potentially infectious period (39.5%, 88 of 223) compared with those of index patients who never wore a mask at home (68.9%, 124 of 180) (p-value <0.01). Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are critical to reducing Omicron transmission in household settings.

      7. Geospatial transmission hotspots of recent HIV infection - Malawi, October 2019-March 2020external icon
        Telford CT, Tessema Z, Msukwa M, Arons MM, Theu J, Bangara FF, Ernst A, Welty S, O'Malley G, Dobbs T, Shanmugam V, Kabaghe A, Dale H, Wadonda-Kabondo N, Gugsa S, Kim A, Bello G, Eaton JW, Jahn A, Nyirenda R, Parekh BS, Shiraishi RW, Kim E, Tobias JL, Curran KG, Payne D, Auld AF.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 4;71(9):329-334.
        Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection.(†) The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)(§) and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission.

      8. Serologic and cytokine signatures in children with multisystem inflammatory syndrome and coronavirus disease 2019external icon
        Lapp SA, Abrams J, Lu AT, Hussaini L, Kao CM, Hunstad DA, Rosenberg RB, Zafferani MJ, Ede KC, Ballan W, Laham FR, Beltran Y, Hsiao HM, Sherry W, Jenkins E, Jones K, Horner A, Brooks A, Bryant B, Meng L, Hammett TA, Oster ME, Bamrah-Morris S, Godfred-Cato S, Belay E, Chahroudi A, Anderson EJ, Jaggi P, Rostad CA.
        Open Forum Infect Dis. 2022 Mar;9(3):ofac070.
        BACKGROUND: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. METHODS: We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. RESULTS: Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]). CONCLUSIONS: MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.

      9. Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with congestive heart failure-United States, 2015-2017external icon
        Kujawski SA, Whitaker M, Ritchey MD, Reingold AL, Chai SJ, Anderson EJ, Openo KP, Monroe M, Ryan P, Bye E, Como-Sabetti K, Barney GR, Muse A, Bennett NM, Felsen CB, Thomas A, Crawford C, Talbot HK, Schaffner W, Gerber SI, Langley GE, Kim L.
        PLoS One. 2022 ;17(3):e0264890.
        BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF. RESULTS: 2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6). CONCLUSIONS: Adults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.

    • Community Health Services
      1. Antiretroviral therapy initiation and retention among clients who received peer-delivered linkage case management and standard linkage services, Eswatini, 2016-2020: retrospective comparative cohort studyexternal icon
        MacKellar D, Hlophe T, Ujamaa D, Pals S, Dlamini M, Dube L, Suraratdecha C, Williams D, Byrd J, Tobias J, Mndzebele P, Behel S, Pathmanathan I, Mazibuko S, Tilahun E, Ryan C.
        Arch Public Health. 2022 Mar 9;80(1):74.
        BACKGROUND: Persons living with HIV infection (PLHIV) who are diagnosed in community settings in sub-Saharan Africa are particularly vulnerable to barriers to care that prevent or delay many from obtaining antiretroviral therapy (ART). METHODS: We conducted a retrospective cohort study to assess if a package of peer-delivered linkage case management and treatment navigation services (CommLink) was more effective than peer-delivered counseling, referral, and telephone follow-up (standard linkage services, SLS) in initiating and retaining PLHIV on ART after diagnosis in community settings in Eswatini. HIV-test records of 773 CommLink and 769 SLS clients aged ≥ 15 years diagnosed between March 2016 and March 2018, matched by urban and rural settings of diagnosis, were selected for the study. CommLink counselors recorded resolved and unresolved barriers to care (e.g., perceived wellbeing, fear of partner response, stigmatization) during a median of 52 days (interquartile range: 35-69) of case management. RESULTS: Twice as many CommLink than SLS clients initiated ART by 90 days of diagnosis overall (88.4% vs. 37.9%, adjusted relative risk (aRR): 2.33, 95% confidence interval (CI): 1.97, 2.77) and during test and treat when all PLHIV were eligible for ART (96.2% vs. 37.1%, aRR: 2.59, 95% CI: 2.20, 3.04). By 18 months of diagnosis, 54% more CommLink than SLS clients were initiated and retained on ART (76.3% vs. 49.5%, aRR: 1.54, 95% CI: 1.33, 1.79). Peer counselors helped resolve 896 (65%) of 1372 identified barriers of CommLink clients. Compared with clients with ≥ 3 unresolved barriers to care, 42% (aRR: 1.42, 95% CI: 1.19, 1.68) more clients with 1-2 unresolved barriers, 44% (aRR: 1.44, 95% CI: 1.25, 1.66) more clients with all barriers resolved, and 54% (aRR: 1.54, 95% CI: 1.30, 1.81) more clients who had no identified barriers were initiated and retained on ART by 18 months of diagnosis. CONCLUSIONS: To improve early ART initiation and retention among PLHIV diagnosed in community settings, HIV prevention programs should consider providing a package of peer-delivered linkage case management and treatment navigation services. Clients with multiple unresolved barriers to care measured as part of that package should be triaged for differentiated linkage and retention services.

      2. Chronic disease management service opportunities for community pharmacists during the COVID-19 pandemicexternal icon
        Dwyer G, Popoola A, Seiler N, Therrien N, Karacuschansky A, Fulmer E, Horton K.
        Prev Chronic Dis. 2022 Mar 3;19:E10.
        Health system disruption caused by the COVID-19 pandemic prompted public health professionals to reevaluate potential barriers and opportunities to community pharmacist provision of chronic disease management services and to identify opportunities for maximizing community pharmacists' impact. Researchers conducted semistructured interviews with representatives from chronic disease prevention and pharmacy practice and policy organizations to identify key themes across multiple interviews and novel responses of interest. Interviewees described a lack of payment models to support pharmacist-provided chronic disease management services but noted opportunities for community pharmacists to demonstrate their value in offering services they are uniquely positioned to provide and to implement better workflow solutions. Successfully demonstrating pharmacists' value and making the case for reimbursement from payors, as well as optimizing pharmacy workflow, are critical to maximizing pharmacists' impact in chronic disease prevention and management.

    • Disease Reservoirs and Vectors
      1. Prevalence and diversity of rotavirus A in pigs: Evidence for a possible reservoir in human infectionexternal icon
        Wu FT, Liu LT, Jiang B, Kuo TY, Wu CY, Liao MH.
        Infect Genet Evol. 2022 Mar;98:105198.
        BACKGROUND: Rotavirus A (RVA) are a group of diverse viruses causing acute gastroenteritis (AGE) in humans and animals. Zoonotic transmission is an important mechanism for rotavirus evolution and strain diversity in humans, but the extent of pigs as a major reservoir for human infection is not clear. METHODS AND FINDINGS: We have surveyed 153 pig farms across Taiwan with a total of 4588 porcine stool samples from three age groups from 2014 to 2017. Nursing piglets (less than one month of age) had higher detection rate for rotavirus than older age groups. Five VP7 (G) genotypes and 5 VP4 (P) genotypes were found in a total of 14 different G/P genotype combinations. In addition, porcine RVA strains had 2 NSP4 (E) genotypes and 3 VP6 (I) genotypes. A P[3]-like genotype was also discovered among strains collected in 2016 and 2017. CONCLUSIONS: Most of the genes from Taiwanese porcine strains clustered with each other and the lineages formed by these strains were distinct from the sequences of numerous regional variants or globally circulating porcine strains, suggesting an independent evolutionary history for Taiwanese rotavirus genotypes. The close relationship among porcine RVA strains and some unique porcine-like genotypes detected sporadically among human children in swine farms illustrates that pigs might serve as a reservoir for potential zoonotic transmission and novel genotype evolution in Taiwan's insular environment.

    • Drug Safety
      1. Evaluating opioid analgesic prescribing limits: A narrative reviewexternal icon
        Seitz AE, Janiszewski KA, Guy GP, Tapscott RT, Einstein EB, Meyer TE, Tierney J, Staffa J, Jones CM, Compton WM.
        Pharmacoepidemiol Drug Saf. 2022 Mar 5.

    • Environmental Health
      1. Identification of profiles and determinants of maternal pregnancy urinary biomarkers of phthalates and replacements in the Illinois Kids Development Studyexternal icon
        Pacyga DC, Haggerty DK, Nicol M, Henning M, Calafat AM, Braun JM, Schantz SL, Strakovsky RS.
        Environ Int. 2022 Mar 2;162:107150.
        BACKGROUND/OBJECTIVES: Pregnant women are exposed to multiple phthalates and their replacements, which are endocrine disrupting chemicals associated with adverse maternal and child health outcomes. Identifying maternal characteristics associated with phthalate/replacement exposure during pregnancy is important. METHODS: We evaluated 13 maternal sociodemographic and lifestyle factors, enrollment year, and conception season as determinants of exposure biomarkers of phthalates and their replacements in 482 pregnant women from the Illinois Kids Development Study (I-KIDS, enrolled 2013-2018). We quantified 19 phthalate/replacement metabolites in pools of five first-morning urines collected across pregnancy. K-means clustering identified women with distinct patterns of biomarker concentrations and principal component analysis (PCA) identified principal component (PC) profiles of biomarkers that exist together. We used multivariable regression models to evaluate associations of predictors with identified k-means clusters and PCs. RESULTS: K-means clustering identified two clusters of women: 1) low phthalate/di(2-ethylhexyl) terephthalate (∑DEHTP) and 2) high phthalate/∑DEHTP biomarker concentrations. PCA identified four PCs with loadings heaviest for biomarkers of plasticizer phthalates [di-isononyl, di-isodecyl, di-n-octyl phthalates] (PC1), of other phthalates [dibenzyl, di-n-butyl, di-iso-butyl phthalates] (PC2), of phthalate replacements [∑DEHTP, di(isononyl) cyclohexane-1,2-dicarboxylate (∑DiNCH)] (PC3), and of monoethyl phthalate [MEP] (PC4). Overall, age, marital status, income, parity, pre-pregnancy BMI, caffeine intake, enrollment year, and conception season were independently associated with k-means cluster membership and at least one PC. Additionally, race/ethnicity, education, employment, pregnancy intention, smoking status, alcohol intake, and diet were associated with at least one PC. For instance, women who conceived in the spring, summer, and/or fall months had lower odds of high phthalate/∑DEHTP cluster membership and had lower plasticizer phthalate, phthalate replacement, and MEP PC scores. CONCLUSIONS: Conception season, enrollment year, and several sociodemographic/lifestyle factors were predictive of phthalate/replacement biomarker profiles. Future studies should corroborate these findings, with a special focus on replacements to which pregnant women are becoming increasingly exposed.

    • Epidemiology and Surveillance
      1. Quality of national disease surveillance reporting before and during COVID-19: A mixed-method study in Indonesiaexternal icon
        Hardhantyo M, Djasri H, Nursetyo AA, Yulianti A, Adipradipta BR, Hawley W, Mika J, Praptiningsih CY, Mangiri A, Prasetyowati EB, Brye L.
        Int J Environ Res Public Health. 2022 ;19(5).
        Background: Global COVID-19 outbreaks in early 2020 have burdened health workers, among them surveillance workers who have the responsibility to undertake routine disease surveillance activities. The aim of this study was to describe the quality of the implementation of Indonesia’s Early Warning and Response Alert System (EWARS) for disease surveillance and to measure the burden of disease surveillance reporting quality before and during the COVID-19 epidemic in Indonesia. Methods: A mixed-method approach was used. A total of 38 informants from regional health offices participated in Focus Group Discussion (FGD) and In-Depth Interview (IDI) for informants from Ministry of Health. The FGD and IDI were conducted using online video communication. Yearly completeness and timeliness of reporting of 34 provinces were collected from the application. Qualitative data were analyzed thematically, and quantitative data were analyzed descriptively. Results: Major implementation gaps were found in poorly distributed human resources and regional infrastructure inequity. National reporting from 2017–2019 showed an increasing trend of completeness (55%, 64%, and 75%, respectively) and timeliness (55%, 64%, and 75%, respectively). However, the quality of the reporting dropped to 53% and 34% in 2020 concomitant with the SARS-CoV2 epidemic. Conclusions: Report completeness and timeliness are likely related to regional infrastructure inequity and the COVID-19 epidemic. It is recommended to increase report capacities with an automatic EWARS application linked systems in hospitals and laboratories. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

      2. Characterising spatial patterns of neglected tropical disease transmission using integrated sero-surveillance in Northern Ghanaexternal icon
        Fornace KM, Senyonjo L, Martin DL, Gwyn S, Schmidt E, Agyemang D, Marfo B, Addy J, Mensah E, Solomon AW, Bailey R, Drakeley CJ, Pullan RL.
        PLoS Negl Trop Dis. 2022 Mar 8;16(3):e0010227.
        BACKGROUND: As prevalence decreases in pre-elimination settings, identifying the spatial distribution of remaining infections to target control measures becomes increasingly challenging. By measuring multiple antibody responses indicative of past exposure to different pathogens, integrated serological surveys enable simultaneous characterisation of residual transmission of multiple pathogens. METHODOLOGY/PRINCIPAL FINDINGS: Here, we combine integrated serological surveys with geostatistical modelling and remote sensing-derived environmental data to estimate the spatial distribution of exposure to multiple diseases in children in Northern Ghana. The study utilised the trachoma surveillance survey platform (cross-sectional two-stage cluster-sampled surveys) to collect information on additional identified diseases at different stages of elimination with minimal additional cost. Geostatistical modelling of serological data allowed identification of areas with high probabilities of recent exposure to diseases of interest, including areas previously unknown to control programmes. We additionally demonstrate how serological surveys can be used to identify areas with exposure to multiple diseases and to prioritise areas with high uncertainty for future surveys. Modelled estimates of cluster-level prevalence were strongly correlated with more operationally feasible metrics of antibody responses. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the potential of integrated serological surveillance to characterise spatial distributions of exposure to multiple pathogens in low transmission and elimination settings when the probability of detecting infections is low.

      3. Study protocol for the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infectionexternal icon
        O'Laughlin KN, Thompson M, Hota B, Gottlieb M, Plumb ID, Chang AM, Wisk LE, Hall AJ, Wang RC, Spatz ES, Stephens KA, Huebinger RM, McDonald SA, Venkatesh A, Gentile N, Slovis BH, Hill M, Saydah S, Idris AH, Rodriguez R, Krumholz HM, Elmore JG, Weinstein RA, Nichol G.
        PLoS One. 2022 ;17(3):e0264260.
        BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODS: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTS: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONS: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

    • Food Safety
      1. Salmonella enterica subspecies enterica serovar Corvallis (S. Corvallis) has been identified as a human pathogen and as a food contaminant. Diarrhoeal disease is a common diagnosis in tourists visiting Southeast Asia, often with unknown aetiology. However, numerous public health institutes have identified Salmonella as a common causative agent when consuming contaminated food and water. Genomic data from environmental isolates from a Cambodian informal market were uploaded to the National Center for Biotechnology Information (NCBI) platform, allowing the novel sequences to be compared to global whole-genome sequence archives. The comparison revealed that two human clinical isolates from England and four of the environmental isolates were closely related, with an average single nucleotide polymorphism (SNP) difference of 1 (0-3 SNPs). A maximum-likelihood tree based on core SNPs was generated comparing the 4 isolates recovered from a Cambodian informal market with 239 isolates of S. Corvallis received from routine surveillance of human salmonellosis in England and confirmed the close relationship. In addition, the environmental isolates clustered into a broader phylogenetic group within the S. Corvallis population containing 68 additional human isolates, of which 42 were from patients who reported recent international travel, almost exclusively to Southeast Asia. The environmental isolates of S. Corvallis isolated from an informal market in Cambodia are concerning for public health due to their genetic similarity to isolates (e.g. clinical isolates from the UK) with known human virulence and pathogenicity. This study emphasizes the benefits of global and public data sharing of pathogen genomes.

    • Genetics and Genomics

      1. The use of whole-genome sequencing by the federal interagency collaboration for Genomics for Food and Feed Safety in the United Statesexternal icon
        Stevens EL, Carleton HA, Beal J, Tillman GE, Lindsey RL, Lauer AC, Pightling A, Jarvis KG, Ottesen A, Ramachandran P, Hintz L, Katz LS, Folster JP, Whichard JM, Trees E, Timme RE, McDermott P, Wolpert B, Bazaco M, Zhao S, Lindley S, Bruce BB, Griffin PM, Brown E, Allard M, Tallent S, Irvin K, Hoffmann M, Wise M, Tauxe R, Gerner-Smidt P, Simmons M, Kissler B, Defibaugh-Chavez S, Klimke W, Agarwala R, Lindsay J, Cook K, Austerman SR, Goldman D, McGarry S, Hale KR, Dessai U, Musser SM, Braden C.
        J Food Prot. 2022 Mar 8.
        This multi-agency report developed under the Interagency Collaboration for Genomics for Food and Feed Safety (Gen-FS) provides an overview of the use of and transition to Whole-Genome Sequencing (WGS) technology to detect and characterize pathogens transmitted commonly by food and identify their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among federal agencies, including the National Institutes of Health (NIH); the Department of Health and Human Services' Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA); and the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS), Agricultural Research Service (ARS), and Animal and Plant Health Inspection Service (APHIS). We describe single nucleotide polymorphism (SNP), core-genome (cg) and whole-genome multi-locus sequence typing (wgMLST) data analysis methods as used in CDC's PulseNet and FDA's GenomeTrakr networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Gen-FS agency partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles), source attribution efforts, and increasing transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information (NCBI). Finally, we highlight the impact of current trends in the use of culture-independent diagnostics tests (CIDT) for human diagnostic testing on analytical approaches related to food safety. Lastly, we highlight what is next for WGS in food safety.

      2. Whole genome analysis of rotavirus strains circulating in Benin before vaccine introduction, 2016-2018external icon
        Agbla JM, Esona MD, Jaimes J, Gautam R, Agbankpé AJ, Katz E, Dougnon TV, Capo-Chichi A, Ouedraogo N, Razack O, Bankolé HS, Bowen MD.
        Virus Res. 2022 Mar 2:198715.
        Species A Rotaviruses (RVA) still play a major role in causing acute diarrhea in children under five years old worldwide. Currently, an 11-gene classification system is used to designate the full genotypic constellations of circulating strains. Viral proteins and non-structural proteins in the order VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 are represented by the genotypes Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx, respectively. In Benin, ROTAVAC® vaccine was introduced into the Expanded Programme on Immunization in December 2019. To monitor circulating RVA strains for changes that may affect vaccine performance, in-depth analysis of strains prior to vaccine introduction are needed. Here we report, the whole-gene characterization (11 ORFs) for 72 randomly selected RVA strains of common and unusual genotypes collected in Benin from the 2016-2018 seasons. The sequenced strains were 15 G1P[8], 20 G2P[4], 5 G9P[8], 14 G12P[8], 9 G3P[6], 2 G1P[6], 3 G2P[6], 2 G9P[4], 1 G12P[6], and 1 G1G9P[8]/P[4]. The study strains exhibited two genetic constellations designed as Wa-like G1/G9/G12-P[6]/P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 and DS-1-like G2/G3/G12-P[4]/P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Genotype G9P[4] strains possessed a DS-1-like genetic constellation with an E6 NSP4 gene, G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E6-H2. The mixed genotype showed both Wa-like and DS-1-like profiles with a T6 NSP3 gene G1/G9P[8]/[4]-I1/I2-R1/R2-C1/C2-M1/M2-A1/A2-N1/N2-T1/T6-E1/E6-H1/H2. At the allelic level, the analysis of the Benin strains, reference strains (with known alleles), vaccine strains (with known alleles) identified 2-13 and 1-17 alleles for DS-1-like and Wa-like strains, respectively. Most of the study strains clustered into previously defined alleles, but we defined 3 new alleles for the VP7 (G3=1 new allele and G12=2 new alleles) and VP4 (P[4]=1 new allele and P[6]=2 new alleles) genes which formed the basis of the VP7 and VP4 gene clusters, respectively. For the remaining 9 genes, 0-6 new alleles were identified for both Wa-like and DS-1-like strains. This analysis of whole genome sequences of RVA strains circulating in Benin described genetic point mutations and reassortment events as well as novel alleles. Further detailed studies on these new alleles are needed and these data can also provide a baseline for studies on RVA in the post-vaccination period.

    • Health Economics
      1. WHO-led consensus statement on vaccine delivery costing: process, methods, and findingsexternal icon
        Levin A, Boonstoppel L, Brenzel L, Griffiths U, Hutubessy R, Jit M, Mogasale V, Pallas S, Resch S, Suharlim C, Yeung KH.
        BMC Med. 2022 Mar 8;20(1):88.
        BACKGROUND: Differences in definitions and methodological approaches have hindered comparison and synthesis of economic evaluation results across multiple health domains, including immunization. At the request of the World Health Organization's (WHO) Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC), WHO convened an ad hoc Vaccine Delivery Costing Working Group, comprising experts from eight organizations working in immunization costing, to address a lack of standardization and gaps in definitions and methodological guidance. The aim of the Working Group was to develop a consensus statement harmonizing terminology and principles and to formulate recommendations for vaccine delivery costing for decision making. This paper discusses the process, findings of the review, and recommendations in the Consensus Statement. METHODS: The Working Group conducted several interviews, teleconferences, and one in-person meeting to identify groups working in vaccine delivery costing as well as existing guidance documents and costing tools, focusing on those for low- and middle-income country settings. They then reviewed the costing aims, perspectives, terms, methods, and principles in these documents. Consensus statement principles were drafted to align with the Global Health Cost Consortium costing guide as an agreed normative reference, and consensus definitions were drafted to reflect the predominant view across the documents reviewed. RESULTS: The Working Group identified four major workstreams on vaccine delivery costing as well as nine guidance documents and eleven costing tools for immunization costing. They found that some terms and principles were commonly defined while others were specific to individual workstreams. Based on these findings and extensive consultation, recommendations to harmonize differences in terminology and principles were made. CONCLUSIONS: Use of standardized principles and definitions outlined in the Consensus Statement within the immunization delivery costing community of practice can facilitate interpretation of economic evidence by global, regional, and national decision makers. Improving methodological alignment and clarity in program costing of health services such as immunization is important to support evidence-based policies and optimal resource allocation. On the other hand, this review and Consensus Statement development process revealed the limitations of our ability to harmonize given that study designs will vary depending upon the policy question that is being addressed and the country context.

      2. Assessing the cost-utility of universal hepatitis B vaccination among adultsexternal icon
        Hall EW, Weng MK, Harris AM, Schillie S, Nelson NP, Ortega-Sanchez IR, Rosenthal E, Sullivan PS, Lopman B, Jones J, Bradley H, Rosenberg ES.
        J Infect Dis. 2022 Mar 9.
        BACKGROUND: Although effective against hepatitis B virus (HBV) infection, hepatitis B (HepB) vaccination is only recommended for infants, children and adults at higher risk. We conducted an economic evaluation of universal HepB vaccination among US adults. METHODS: Using a decision analytic model with Markov disease progression, we compared current vaccination recommendations (baseline) with either 3-dose or 2-dose universal HepB vaccination (intervention strategies). In simulated modeling of one million adults distributed by age and risk groups, we quantified health benefits (quality-adjusted life years, QALYs) and costs for each strategy. Multivariable probabilistic sensitivity analyses identified key inputs. All costs reported in 2019 US dollars. RESULTS: With incremental base-case vaccination coverage up to 50% among persons at lower risk and 0% increment among persons at higher risk, each of two intervention strategies averted nearly one quarter of acute HBV infections (3-dose strategy: 24.8%; 2-dose strategy: 24.6%). Societal incremental cost per QALY gained of $152,722 (Interquartile range: $119,113, $235,086) and $155,429 (Interquartile range: $120,302, $242,226) were estimated for 3-dose and 2-dose strategies, respectively. Risk of acute HBV infection showed the strongest influence. CONCLUSIONS: Universal adult vaccination against HBV may be an appropriate strategy for reducing HBV incidence and improving resulting health outcomes.

      3. Trends in prevalence and treatment of diabetic macular edema and vision-threatening diabetic retinopathy among Medicare Part B fee-for-service beneficiariesexternal icon
        Lundeen EA, Andes LJ, Rein DB, Wittenborn JS, Erdem E, Gu Q, Saaddine J, Imperatore G, Chew EY.
        JAMA Ophthalmol. 2022 Mar 3.
        IMPORTANCE: While diabetes prevalence among US adults has increased in recent decades, few studies document trends in diabetes-related eye disease. OBJECTIVE: To examine 10-year trends (2009-2018) in annual prevalence of Medicare beneficiaries with diabetes with a diagnosis of diabetic macular edema (DME) or vision-threatening diabetic retinopathy (VTDR) and trends in treatment. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study using Centers for Medicare & Medicaid Services research identifiable files, data for patients 65 years and older were analyzed from claims. Beneficiaries were continuously enrolled in Medicare Part B fee-for-service (FFS) insurance for the calendar year and had a diagnosis of diabetes on 1 or more inpatient claims or 2 or more outpatient claims during the calendar year or a 1-year look-back period. MAIN OUTCOMES AND MEASURES: Using diagnosis and procedure codes, annual prevalence was determined for beneficiaries with 1 or more claims for (1) any DME, (2) either DME or VTDR, and (3) anti-vascular endothelial growth factor (VEGF) injections, laser photocoagulation, or vitrectomy, stratified by any DME, VTDR with DME, and VTDR without DME. Racial and ethnic disparities in diagnosis and treatment are presented for 2018. RESULTS: In 2018, 6 960 823 beneficiaries (27.4%) had diabetes; half were aged 65 to 74 years (49.7%), half (52.7%) were women, and 75.7% were non-Hispanic White. From 2009 to 2018, there was an increase in the annual prevalence of beneficiaries with diabetes who had 1 or more claims for any DME (1.0% to 3.3%) and DME/VTDR (2.8% to 4.3%). Annual prevalence of anti-VEGF increased, particularly among patients with any DME (15.7% to 35.2%) or VTDR with DME (20.2% to 47.6%). Annual prevalence of laser photocoagulation decreased among those with any DME (45.5% to 12.5%), VTDR with DME (54.0% to 20.3%), and VTDR without DME (22.5% to 5.8%). Among all 3 groups, prevalence of vitrectomy in 2018 was less than half that in 2009. Prevalence of any DME and DME/VTDR was highest among Hispanic beneficiaries (5.0% and 7.0%, respectively) and Black beneficiaries (4.5% and 6.2%, respectively) and lowest among non-Hispanic White beneficiaries (3.0% and 3.8%, respectively). Among those with DME/VTDR, anti-VEGF was most prevalent among non-Hispanic White beneficiaries (30.3%). CONCLUSIONS AND RELEVANCE: From 2009 to 2018, prevalence of DME or VTDR increased among Medicare Part B FFS beneficiaries alongside an increase in anti-VEGF treatment and a decline in laser photocoagulation and vitrectomy.

    • Health Equity and Health Disparities
      1. Disparities in COVID-19 vaccination coverage between urban and rural counties - United States, December 14, 2020-January 31, 2022external icon
        Saelee R, Zell E, Murthy BP, Castro-Roman P, Fast H, Meng L, Shaw L, Gibbs-Scharf L, Chorba T, Harris LQ, Murthy N.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 4;71(9):335-340.
        Higher COVID-19 incidence and mortality rates in rural than in urban areas are well documented (1). These disparities persisted during the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variant surges during late 2021 and early 2022 (1,2). Rural populations tend to be older (aged ≥65 years) and uninsured and are more likely to have underlying medical conditions and live farther from facilities that provide tertiary medical care, placing them at higher risk for adverse COVID-19 outcomes (2). To better understand COVID-19 vaccination disparities between urban and rural populations, CDC analyzed county-level vaccine administration data among persons aged ≥5 years who received their first dose of either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccine or a single dose of the Ad.26.COV2.S (Janssen [Johnson & Johnson]) COVID-19 vaccine during December 14, 2020-January 31, 2022, in 50 states and the District of Columbia (DC). COVID-19 vaccination coverage with ≥1 doses in rural areas (58.5%) was lower than that in urban counties (75.4%) overall, with similar patterns across age groups and sex. Coverage with ≥1 doses varied among states: 46 states had higher coverage in urban than in rural counties, one had higher coverage in rural than in urban counties. Three states and DC had no rural counties; thus, urban-rural differences could not be assessed. COVID-19 vaccine primary series completion was higher in urban than in rural counties. However, receipt of booster or additional doses among primary series recipients was similarly low between urban and rural counties. Compared with estimates from a previous study of vaccine coverage among adults aged ≥18 years during December 14, 2020-April 10, 2021, these urban-rural disparities among those now eligible for vaccination (aged ≥5 years) have increased more than twofold through January 2022, despite increased availability and access to COVID-19 vaccines. Addressing barriers to vaccination in rural areas is critical to achieving vaccine equity, reducing disparities, and decreasing COVID-19-related illness and death in the United States (2).

    • Immunity and Immunization
      1. Safety monitoring of COVID-19 Vaccine booster doses among persons aged 12-17 years - United States, December 9, 2021-February 20, 2022external icon
        Hause AM, Baggs J, Marquez P, Abara WE, Olubajo B, Myers TR, Su JR, Thompson D, Gee J, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 4;71(9):347-351.
        As of February 20, 2022, only BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine has been authorized for use in persons aged 12-17 years in the United States (1). The Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for Pfizer-BioNTech vaccine on December 9, 2021, to authorize a homologous* booster dose for persons aged 16-17 years ≥6 months after receipt of dose 2 (1). On January 3, 2022, authorization was expanded to include persons aged 12-15 years, and for all persons aged ≥12 years, the interval between dose 2 and booster dose was shortened to ≥5 months (1). To characterize the safety of Pfizer-BioNTech booster doses among persons aged 12-17 years (adolescents), CDC reviewed adverse events and health impact assessments during the week after receipt of a homologous Pfizer-BioNTech booster dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system managed by CDC and FDA. During December 9, 2021-February 20, 2022, approximately 2.8 million U.S. adolescents received a Pfizer-BioNTech booster dose.(†) During this period, receipt of 3,418 Pfizer-BioNTech booster doses were reported to v-safe for adolescents. Reactions were reported to v-safe with equal or slightly higher frequency after receipt of a booster dose than after dose 2, were primarily mild to moderate in severity, and were most frequently reported the day after vaccination. VAERS received 914 reports of adverse events after Pfizer-BioNTech booster dose vaccination of adolescents; 837 (91.6%) were nonserious and 77 (8.4%) were serious. Health care providers, parents, and adolescents should be advised that local and systemic reactions are expected among adolescents after homologous Pfizer-BioNTech booster vaccination, and that serious adverse events are rare.

      2. Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA vaccination in preventing COVID-19-associated emergency department and urgent care encounters and hospitalizations among nonimmunocompromised children and adolescents Aged 5-17 Years - VISION Network, 10 States, April 2021-January 2022external icon
        Klein NP, Stockwell MS, Demarco M, Gaglani M, Kharbanda AB, Irving SA, Rao S, Grannis SJ, Dascomb K, Murthy K, Rowley EA, Dalton AF, DeSilva MB, Dixon BE, Natarajan K, Stenehjem E, Naleway AL, Lewis N, Ong TC, Patel P, Konatham D, Embi PJ, Reese SE, Han J, Grisel N, Goddard K, Barron MA, Dickerson M, Liao IC, Fadel WF, Yang DH, Arndorfer J, Fireman B, Griggs EP, Valvi NR, Hallowell C, Zerbo O, Reynolds S, Ferdinands J, Wondimu MH, Williams J, Bozio CH, Link-Gelles R, Azziz-Baumgartner E, Schrag SJ, Thompson MG, Verani JR.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 4;71(9):352-358.
        The efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine against laboratory-confirmed COVID-19 exceeded 90% in clinical trials that included children and adolescents aged 5-11, 12-15, and 16-17 years (1-3). Limited real-world data on 2-dose mRNA vaccine effectiveness (VE) in persons aged 12-17 years (referred to as adolescents in this report) have also indicated high levels of protection against SARS-CoV-2 (the virus that causes COVID-19) infection and COVID-19-associated hospitalization (4-6); however, data on VE against the SARS-CoV-2 B.1.1.529 (Omicron) variant and duration of protection are limited. Pfizer-BioNTech VE data are not available for children aged 5-11 years. In partnership with CDC, the VISION Network* examined 39,217 emergency department (ED) and urgent care (UC) encounters and 1,699 hospitalizations(†) among persons aged 5-17 years with COVID-19-like illness across 10 states during April 9, 2021-January 29, 2022,(§) to estimate VE using a case-control test-negative design. Among children aged 5-11 years, VE against laboratory-confirmed COVID-19-associated ED and UC encounters 14-67 days after dose 2 (the longest interval after dose 2 in this age group) was 46%. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 83% and 76%, respectively; VE ≥150 days after dose 2 was 38% and 46%, respectively. Among adolescents aged 16-17 years, VE increased to 86% ≥7 days after dose 3 (booster dose). VE against COVID-19-associated ED and UC encounters was substantially lower during the Omicron predominant period than the B.1.617.2 (Delta) predominant period among adolescents aged 12-17 years, with no significant protection ≥150 days after dose 2 during Omicron predominance. However, in adolescents aged 16-17 years, VE during the Omicron predominant period increased to 81% ≥7 days after a third booster dose. During the full study period, including pre-Delta, Delta, and Omicron predominant periods, VE against laboratory-confirmed COVID-19-associated hospitalization among children aged 5-11 years was 74% 14-67 days after dose 2, with wide CIs that included zero. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 92% and 94%, respectively; VE ≥150 days after dose 2 was 73% and 88%, respectively. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12-17 years.

      3. Notes from the field: Readiness for use of type 2 novel oral poliovirus vaccine in response to a type 2 circulating vaccine-derived poliovirus outbreak - Tajikistan, 2020-2021external icon
        O'Connor P, Huseynov S, Nielsen CF, Saidzoda F, Saxentoff E, Sadykova U, Kormoss P.
        MMWR Morb Mortal Wkly Rep. 2022 Mar 4;71(9):361-362.

      4. Estimating the number of symptomatic SARS-CoV-2 infections among vaccinated individuals in the United States-January-July, 2021external icon
        Kugeler KJ, Williamson J, Curns AT, Healy JM, Nolen LD, Clark TA, Martin SW, Fischer M.
        PLoS One. 2022 ;17(3):e0264179.
        As of March 2021, three COVID-19 vaccines had been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic COVID-19 cases among vaccinated people (vaccine breakthrough infections) based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 199,000 symptomatic vaccine breakthrough infections (95% CI: ~183,000-214,000 cases) occurred in the United States during January-July 2021 among >156 million fully vaccinated people. With high SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.

      5. Influenza and pneumococcal vaccination among male veterans and nonveterans, 2016-2018external icon
        Boersma P, Cohen RA, Zelaya CE, Moy E.
        Public Health Rep. 2022 Mar 3:333549221081119.
        OBJECTIVES: The Advisory Committee on Immunization Practices recommends persons aged ≥6 months receive an influenza vaccination annually, and certain adults aged ≥19 years receive the 23-valent pneumococcal polysaccharide vaccine alone or in series with the 13-valent pneumococcal conjugate vaccine, depending on age, chronic conditions, and smoking status. This study examines the prevalence of influenza and pneumococcal vaccination relative to Healthy People 2020 goals to understand how vaccination receipt differs by veteran status and sociodemographic subgroups. METHODS: We analyzed pooled data from the 2016-2018 National Health Interview Survey (N = 35 094) in 2021 to estimate the prevalence of influenza and pneumococcal vaccination for men aged 25-64 years and for men aged ≥65 years by veteran status and selected sociodemographic subgroups. We used 2-tailed t tests with an α = .05 to identify significant differences. RESULTS: Among men, 44.7% of veterans and 33.5% of nonveterans aged 25-64 years and 71.0% of veterans and 64.9% of nonveterans aged ≥65 years received an influenza vaccine in the past year. Among men aged 25-64 years at high risk for pneumococcal disease, 35.9% of veterans and 20.8% of nonveterans had ever received ≥1 dose of any pneumococcal vaccination. Disparities in the prevalence of vaccination within examined sociodemographic characteristics were often smaller in magnitude among veterans than among nonveterans for both vaccinations. CONCLUSIONS: Vaccination rates were below Healthy People 2020 targets for both groups, except influenza vaccination among veterans aged ≥65 years. Understanding differences in vaccine uptake may inform efforts to improve vaccination rates by identifying subgroups who are at high risk of disease and have low vaccination rates.

      6. Modeling strategies for the allocation of SARS-CoV-2 vaccines in the United Statesexternal icon
        Walker J, Paul P, Dooling K, Oliver S, Prasad P, Steele M, Gastañaduy PA, Johansson MA, Biggerstaff M, Slayton RB.
        Vaccine. 2022 Feb 7.
        The Advisory Committee on Immunization Practices (ACIP) recommended phased allocation of SARS-CoV-2 vaccines in December 2020. To support the development of this guidance, we used a mathematical model of SARS-CoV-2 transmission to evaluate the relative impact of three vaccine allocation strategies on infections, hospitalizations, and deaths. All three strategies initially prioritized healthcare personnel (HCP) for vaccination. Strategies of subsequently prioritizing adults aged ≥65 years, or a combination of essential workers and adults aged ≥75 years, prevented the most deaths. Meanwhile, prioritizing adults with high-risk medical conditions immediately after HCP prevented the most infections. All three strategies prevented a similar fraction of hospitalizations. While no model is capable of fully capturing the complex social dynamics which shape epidemics, exercises such as this one can be a useful way for policy makers to formalize their assumptions and explore the key features of a problem before making decisions.

      7. Functional antibody-dependent cell mediated cytotoxicity (ADCC) responses to vaccine and circulating influenza strains following vaccinationexternal icon
        Chen X, Sun HY, Lee CY, Rostad CA, Trost J, Abreu RB, Carlock MA, Wilson JR, Gansebom S, Ross TM, Steinhauer DA, Anderson EJ, Anderson LJ.
        Virology. 2022 Feb 24;569:44-55.
        Novel cell-based assays were developed to assess antibody-dependence cellular cytotoxicity (ADCC) antibodies against both vaccine and a representative circulation strain HA and NA proteins for the 2014-15 influenza season. The four assays using target cells stably expressing one of the four proteins worked well. In pre- and post-vaccine sera from 70 participants in a pre-season vaccine trial, we found ADCC antibodies and a rise in ADCC antibody titer against target cells expressing the 4 proteins but a much higher titer for the vaccine than the circulating HA in both pre-and post-vaccine sera. These differences in HA ADCC antibodies were not reflected in differences in HA binding antibodies. Our observations suggested that relatively minor changes on the subtype HA can result in large differences in ADCC activity.

    • Injury and Violence
      1. Rural-urban comparisons in the rates of self-harm, U.S., 2018external icon
        Wang J, Brown MM, Ivey-Stephenson AZ, Xu L, Stone DM.
        Am J Prev Med. 2022 Mar 3.
        INTRODUCTION: This study compares rural and urban differences in the rates of nonfatal self-harm in the U.S. in 2018. METHODS: Nationwide Emergency Department Sample and Census data were analyzed to calculate the RR of emergency department visits for self-harm between rural and urban residents. The analyses were conducted in 2021. RESULTS: Among a weighted total of 488,000 emergency department visits for self-harm in the U.S., 80.5% were urban residents, and 18.3% were rural residents. In both settings, poisoning was the most common mechanism for self-harm, followed by cutting. Firearm-related self-harm and suffocation each accounted for <2% of total self-harm cases. Overall, the age-adjusted emergency department visit rate for self-harm was 252.3 per 100,000 for rural residents, which was 1.5 (95% CI=1.4, 1.6) times greater than the rate for urban residents (170.8 per 100,000 residents). The rates of self-harm among rural residents were higher than those of urban residents for both male and female residents, for all age groups except people aged ≥65 years, and by all mechanisms. CONCLUSIONS: Comprehensive suicide prevention strategies tailored to rural communities may mitigate the rural-urban disparity in morbidity from suicidal behavior.

    • Laboratory Sciences
      1. Software testing in microbial bioinformatics: A call to actionexternal icon
        van der Putten BC, Mendes CI, Talbot BM, de Korne-Elenbaas J, Mamede R, Vila-Cerqueira P, Coelho LP, Gulvik CA, Katz LS, The Asm Ngs Hackathon P.
        Microb Genom. 2022 Mar;8(3).
        Computational algorithms have become an essential component of research, with great efforts by the scientific community to raise standards on development and distribution of code. Despite these efforts, sustainability and reproducibility are major issues since continued validation through software testing is still not a widely adopted practice. Here, we report seven recommendations that help researchers implement software testing in microbial bioinformatics. We have developed these recommendations based on our experience from a collaborative hackathon organised prior to the American Society for Microbiology Next Generation Sequencing (ASM NGS) 2020 conference. We also present a repository hosting examples and guidelines for testing, available from https://github.com/microbinfie-hackathon2020/CSIS.

      2. Specimen self-collection for SARS-CoV-2 testing: Patient performance and preferences-Atlanta, Georgia, August-October 2020external icon
        O'Laughlin K, Espinosa CC, Smith-Jeffcoat SE, Koh M, Khalil GM, Hoffman A, Rebolledo PA, Schechter MC, Stewart RJ, da Silva J, Biedron C, Bankamp B, Folster J, Gargis AS, Bowen MD, Paulick A, Wang YF, Tate JE, Kirking HL.
        PLoS One. 2022 ;17(3):e0264085.
        Self-collected specimens can expand access to SARS-CoV-2 testing. At a large inner-city hospital 1,082 participants self-collected saliva and anterior nasal swab (ANS) samples before healthcare workers collected nasopharyngeal swab (NPS) samples on the same day. To characterize patient preferences for self-collection, this investigation explored ability, comfort, and ease of ANS and saliva self-collection for SARS-CoV-2 testing along with associated patient characteristics, including medical history and symptoms of COVID-19. With nearly all participants successfully submitting a specimen, favorable ratings from most participants (at least >79% in ease and comfort), and equivocal preference between saliva and ANS, self-collection is a viable SARS-CoV-2 testing option.

    • Maternal and Child Health
      1. Key predictors of primary care providers' self-efficacy in caring for children with overweight or obesityexternal icon
        Liebhart JL, Goodman AB, Lindros J, Krafft C, Cook SR, Baker A, Hassink SG.
        Acad Pediatr. 2022 Mar 2.
        OBJECTIVE: Self-efficacy is a crucial factor in enabling pediatric primary care providers (PCPs) to deliver recommended care to children with overweight and obesity. This study, conducted with a large, national sample of PCPs, aimed to identify key factors which may contribute to PCP self-efficacy for obesity-related care, from a list of previously reported barriers and facilitators. METHODS: A national random sample of American Academy of Pediatrics members were surveyed in 2017 (analytic n=704). Factor analysis was used to identify self-efficacy variables from relevant indicators and assess fit. Multivariable linear regression analyses were conducted to identify key predictors of PCP self-efficacy from reported facilitators or barriers to care, including characteristics of the PCP, practice, community, and payment systems. RESULTS: Two PCP self-efficacy variables were identified: health risk assessment and patient-centered counseling. Both were positively predicted by relevant training, the belief that pediatricians play an important role in obesity, and awareness of barriers to payment for dietitians or weight management programs. Both were negatively predicted by a perceived lack of available PCP time for counseling and inadequacy of available referral resources to assist with treatment. Additional predictors of counseling self-efficacy included PCP beliefs that they are paid for treatment (+) and that patients/families lack time for healthy behaviors (-). Electronic health record clinical decision supports or registries and patient social disadvantage were not predictive. CONCLUSIONS: Results suggest multiple potential roles and strategies for local and national organizations seeking to facilitate improvements to PCP self-efficacy in caring for children with overweight and obesity.

      2. WHO method for estimating congenital syphilis to inform surveillance and service provision, Paraguayexternal icon
        Heath K, Alonso M, Aguilar G, Samudio T, Korenromp E, Rowley J, Suleiman A, Shwe YY, Htin KC, Ishikawa N, Owiredu MN, Taylor M.
        Bull World Health Organ. 2022 Mar 1;100(3):231-236.
        PROBLEM: In Paraguay, incomplete surveillance data resulted in the burden of congenital syphilis being underestimated, which, in turn, led to missed opportunities for infant diagnosis and treatment. APPROACH: The prevalence of congenital syphilis, as defined by the World Health Organization (WHO), was estimated for Paraguay using the WHO congenital syphilis estimation tool. This tool was also used to monitor progress towards the elimination of mother-to-child transmission of syphilis. LOCAL SETTING: The burden of syphilis in Paraguay has historically been high: its prevalence in pregnant women was estimated to be 3% in 2018. RELEVANT CHANGES: The incidence rate of congenital syphilis estimated using the WHO tool was around nine times the reported prevalence. Subsequently, Paraguay: (i) provided training to improve diagnosis and case reporting; (ii) strengthened information systems for case monitoring and reporting; and (iii) procured additional rapid dual HIV-syphilis and rapid plasma reagin tests to increase syphilis testing capacity. In addition, the Ministry of Health prepared a new national plan for eliminating mother-to-child transmission of syphilis, with clear monitoring milestones. LESSONS LEARNT: Health-care providers' reporting and surveillance procedures for congenital syphilis may not adequately reflect national and international case definitions. Use of the WHO congenital syphilis estimation tool in Paraguay drew attention to congenital syphilis as a national public health problem and highlighted the importance of comprehensive national surveillance systems and accurate data. Ongoing use of the WHO tool can track progress towards the elimination of mother-to-child transmission of syphilis by helping improve syphilis service coverage and national surveillance.

      3. Children who are nurtured, protected, and supported in the first years of life tend to have better individual outcomes and are more likely to grow to become healthy, productive adults. Child well-being varies across states, yet the field lacks a comprehensive review of infant and toddler indicators measured at the state-level. This paper reviews indicators of well-being from the prenatal period to three years that meet certain a priori criteria. Most of the child-level indicators identified were in the physical health domain; relatively fewer indicators were found in the early cognition and language or social-emotional-behavioral domains. While some states are making progress toward developing integrated early childhood data systems, more work is needed to provide robust data on infant and toddler development. These results highlight the need to develop a broader range of indicators of infant and toddler well-being and improve measurement sources to better inform policies and programs advancing population health. © 2022, The Author(s).

      4. Maternity care practices and breastfeeding intentions at one month among low-income womenexternal icon
        Beauregard JL, Nelson JM, Li R, Perrine CG, Hamner HC.
        Pediatrics. 2022 Mar 7.
        BACKGROUND: Maternity care practices have been linked with higher chances of meeting breastfeeding intentions, but this relationship has not been examined using national data on US low-income women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: Using data from the WIC Infant and Toddler Feeding Practices Study-2 on 1080 women who intended to breastfeed, we estimated risk ratios for associations between (1) each of 6 maternity care practices supportive of breastfeeding (breastfeeding within 1 hour of birth, showing mothers how to breastfeed, giving only breast milk, rooming-in, breastfeeding on demand, no pacifiers), (2) each practice adjusted for all other practices, and (3) total number of practices experienced with whether women met their intention to feed only breast milk at 1 month old. Models were adjusted for demographics. RESULTS: In adjusted models (1), breastfeeding within 1 hour of birth, giving only breast milk, and no pacifiers were associated with higher likelihood of meeting prenatal breastfeeding intentions. Adjusting for all other practices (2), initiating breastfeeding within 1 hour of birth (risk ratio: 1.3; 95% confidence interval: 1.0-1.6) and giving only breast milk (risk ratio: 4.4; 95% confidence interval: 3.4-5.7) remained associated with meeting breastfeeding intention. There was a dose-response relationship between number of steps experienced and higher likelihood of meeting prenatal breastfeeding intentions (3). CONCLUSIONS: Women who experienced maternity care practices supportive of breastfeeding were more likely to meet their prenatal breastfeeding intentions, underscoring the importance of breastfeeding support during the birth hospitalization in enabling mothers to achieve their breastfeeding goals.

    • Medicine
      1. Urethrocutaneous fistula following VMMC: a case series from March 2013 to October 2019 in ZAZIC's voluntary medical male circumcision program in Zimbabweexternal icon
        Murenje V, Omollo V, Gonouya P, Hove J, Munyaradzi T, Marongwe P, Tshimanga M, Chitimbire V, Xaba S, Mandisarisa J, Balachandra S, Makunike-Chikwinya B, Holec M, Mangwiro T, Barnhart S, Feldacker C.
        BMC Urol. 2022 Feb 16;22(1):20.
        BACKGROUND: Urethrocutaneous fistula (subsequently, fistula) is a rare adverse event (AE) in voluntary medical male circumcision (VMMC) programs. Global fistula rates of 0.19 and 0.28 per 100,000 VMMCs were reported. Management of fistula can be complex and requires expert skills. We describe seven cases of fistula in our large-scale VMMC program in Zimbabwe. We present fistula rates; provide an overview of initial management, surgical interventions, and patient outcomes; discuss causes; and suggest future prevention efforts. RESULTS: Case details are presented on fistulas identified between March 2013 and October 2019. Among the seven fistula clients, ages ranged from 10 to 22 years; 6 cases were among boys under 15 years of age. All clients received surgical VMMC by trained providers in an outreach setting. Clients presented with fistulae 2-42 days after VMMC. Secondary infection was identified in 6 of 7 cases. Six cases were managed through surgical repair. The number of repair attempts ranged from 1 to 10. One case healed spontaneously with conservative management. Fistula rates are presented as cases/100,000 VMMCs. CONCLUSION: Fistula is an uncommon but severe AE that requires clinical expertise for successful management and repair. High-quality AE surveillance should identify fistula promptly and include consultation with experienced urologists. Strengthening provider surgical skills and establishment of standard protocols for fistula management would aid future prevention efforts in VMMC programs.

    • Occupational Safety and Health
      1. Like their counterparts in healthcare, workers in medical examiner and coroners' offices are considered essential workers. The frequency and urgency of their work during the coronavirus disease 2019 (COVID-19) pandemic have only become of greater importance. Because of the increased mortality in the general population due to SARS-CoV-2, the virus that causes COVID-19, it is reasonable to assume that the workload and risk of occupational exposure to SARS-CoV-2 has increased for these workers who are required by state law to investigate deaths known or suspected to be due to a contagious disease that constitutes a public hazard. Studies investigating the impact of the COVID-19 pandemic on these workers and their operations have been limited. The objective of this study was to conduct an assessment of routine medical examiner and coroners' office duties (e.g., infectious disease testing and decedent transport) by surveying the 67 county medical examiner and coroners' offices in Pennsylvania to characterize how the rise in infectious disease cases from COVID-19 influenced workload and resource needs. Quantitative results demonstrated an increase in workload and use of personal protective equipment (PPE) while engineering control usage remained the same. Qualitative results revealed various challenges experienced by the offices during the pandemic including limitations in access to PPE, insufficient storage space for increased numbers of decedents, personnel shortage/burnout, and limited or no engagement at the state level for emergency response planning and implementation. These data are valuable to inform the need for additional guidance or supplies and may be used to optimize resource planning and implementation (e.g., personnel, facilities, and supplies) for both routine and surge demand scenarios.

    • Parasitic Diseases
      1. Factors associated with knowledge about malaria prevention among women of reproductive age, Tete Province, Mozambique, 2019-2020external icon
        Afai G, Rossetto EV, Baltazar CS, Candrinho B, Saifodine A, Zulliger R.
        Malar J. 2022 Mar 5;21(1):76.
        BACKGROUND: Mozambique is a malaria endemic country with an estimated prevalence of malaria in children 6-59 months old that is twice as high in rural areas (46.0%) as in urban areas (18.0%). However, only 46.0% of women aged 15-49 years had complete knowledge about malaria in 2018. This study aimed to identify the factors associated with malaria knowledge among women of reproductive age in a high malaria burden district. METHODS: Data from a cross-sectional study, using a population-based malaria research study in Mágoe District, 2019, were analysed. This analysis included women aged 15-49 years. A multivariate logistic regression model was developed to determine factors associated with complete knowledge of malaria that calculated adjusted odds ratio (aOR) and 95% confidence interval (CI) at a p < 0.05 significance level. Complete malaria knowledge was defined as when a woman correctly identified: fever as a malaria symptom, mosquito bites as the means of malaria transmission, mosquito nets as a tool for malaria prevention, malaria as curable, and were able to name an anti-malarial. RESULTS: A total of 1899 women were included in this analysis. There was complete malaria knowledge among 49% of the respondents. Seventy one percent mentioned fever as one of malaria symptoms, 92% mentioned mosquito bite as the cause of malaria infection, 94% identified that mosquito nets prevent malaria, 92% agreed that malaria has cure, and 76% were able to name at least one anti-malarial medicine. In the multivariate analysis, the following characteristics were associated with significantly higher odds of having complete malaria knowledge: having a secondary school or above education level (adjusted Odds Ratio, aOR = 2.5 CI [1.3-4.6] p = 0.005), being from the middle socioeconomic status group (aOR = 1.5 CI [1.1-2.1] p = 0.005), being from older age group of 35-39 (aOR = 1.9; CI [1.1-3.1] p < 0.001), having 1-2 children (aOR = 1.8; CI [1.2-2.6] p = 0.003), and having interviews completed in Portuguese or Cinyungwe (aOR = 2.3; CI [1.3-4.1] p = 0.004 and aOR = 2.1; CI [1.5-2.8] p < 0.001, respectively). CONCLUSION: Most women in this study had some malaria knowledge, but gaps in complete knowledge remained. In order to broaden knowledge, educational messages about malaria prevention should be more effectively targeted to reach younger, less-educated women and in non-dominant languages.

      2. Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015external icon
        Leonard CM, Assefa A, McCaffery JN, Herman C, Plucinski M, Sime H, Mohammed H, Kebede A, Solomon H, Haile M, Murphy M, Hwang J, Rogier E.
        Malar J. 2022 Mar 4;21(1):70.
        BACKGROUND: Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting. METHODS: The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual's RDT results. Dose-response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey. RESULTS: Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively). CONCLUSIONS: There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings.

    • Physical Activity
      1. Daily steps and all-cause mortality: a meta-analysis of 15 international cohortsexternal icon
        Paluch AE, Bajpai S, Bassett DR, Carnethon MR, Ekelund U, Evenson KR, Galuska DA, Jefferis BJ, Kraus WE, Lee IM, Matthews CE, Omura JD, Patel AV, Pieper CF, Rees-Punia E, Dallmeier D, Klenk J, Whincup PH, Dooley EE, Pettee Gabriel K, Palta P, Pompeii LA, Chernofsky A, Larson MG, Vasan RS, Spartano N, Ballin M, Nordström P, Nordström A, Anderssen SA, Hansen BH, Cochrane JA, Dwyer T, Wang J, Ferrucci L, Liu F, Schrack J, Urbanek J, Saint-Maurice PF, Yamamoto N, Yoshitake Y, Newton RL, Yang S, Shiroma EJ, Fulton JE.
        Lancet Public Health. 2022 Mar;7(3):e219-e228.
        BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention.

    • Substance Use and Abuse
      1. Pulmonary and critical care considerations for e-cigarette, or vaping, product use-associated lung injury (EVALI)external icon
        Hayes D, Board A, Calfee C, Ellington S, Pollack LA, Kathuria H, Eakin MN, Weissman DN, Callahan SJ, Esper AM, Crotty Alexander LE, Sharma NS, Meyer NJ, Smith LS, Novosad S, Evans ME, Goodman AB, Click ES, Robinson RT, Ewart G, Twentyman E.
        Chest. 2022 Mar 4.
        BACKGROUND: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than half of these patients required admission to an intensive care unit (ICU). METHODS: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, we examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts. RESULTS: Of the 2,708 confirmed or probable EVALI patients requiring hospitalization as of January 21, 2020, 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%), and in severe cases required intubation (36.1%), or extracorporeal membrane oxygenation (ECMO) (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antivirals, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and ECMO; and patient outcomes. CONCLUSIONS: Review of the clinical course of EVALI patients requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. As a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.

      2. Concerns among people who use opioids during the COVID-19 pandemic: a natural language processing analysis of social media postsexternal icon
        Sarker A, Nataraj N, Siu W, Li S, Jones CM, Sumner SA.
        Subst Abuse Treat Prev Policy. 2022 Mar 5;17(1):16.
        BACKGROUND: Timely data from official sources regarding the impact of the COVID-19 pandemic on people who use prescription and illegal opioids is lacking. We conducted a large-scale, natural language processing (NLP) analysis of conversations on opioid-related drug forums to better understand concerns among people who use opioids. METHODS: In this retrospective observational study, we analyzed posts from 14 opioid-related forums on the social network Reddit. We applied NLP to identify frequently mentioned substances and phrases, and grouped the phrases manually based on their contents into three broad key themes: (i) prescription and/or illegal opioid use; (ii) substance use disorder treatment access and care; and (iii) withdrawal. Phrases that were unmappable to any particular theme were discarded. We computed the frequencies of substance and theme mentions, and quantified their volumes over time. We compared changes in post volumes by key themes and substances between pre-COVID-19 (1/1/2019-2/29/2020) and COVID-19 (3/1/2020-11/30/2020) periods. RESULTS: Seventy-seven thousand six hundred fifty-two and 119,168 posts were collected for the pre-COVID-19 and COVID-19 periods, respectively. By theme, posts about treatment and access to care increased by 300%, from 0.631 to 2.526 per 1000 posts between the pre-COVID-19 and COVID-19 periods. Conversations about withdrawal increased by 812% between the same periods (0.026 to 0.235 per 1,000 posts). Posts about drug use did not increase (0.219 to 0.218 per 1,000 posts). By substance, among medications for opioid use disorder, methadone had the largest increase in conversations (20.751 to 56.313 per 1,000 posts; 171.4% increase). Among other medications, posts about diphenhydramine exhibited the largest increase (0.341 to 0.927 per 1,000 posts; 171.8% increase). CONCLUSIONS: Conversations on opioid-related forums among people who use opioids revealed increased concerns about treatment and access to care along with withdrawal following the emergence of COVID-19. Greater attention to social media data may help inform timely responses to the needs of people who use opioids during COVID-19.

      3. High-risk injection-related practices associated with anti-HCV positivity among young adults seeking services in three small cities in Wisconsinexternal icon
        Rogers-Brown J, Sublett F, Canary L, Rein DB, Bhat M, Thompson WW, Vellozzi C, Asher A.
        Subst Use Misuse. 2022 Mar 4:1-9.
        BACKGROUND: Hepatitis C virus (HCV) infection has been increasing among people who inject drugs (PWID), younger than 30 years, and living in rural or suburban areas. We examined injection-related behaviors of young PWID to determine factors associated with HCV infection. METHODS: From September 2013-May 2015, respondent-driven and snowball sampling were used in 3 suburban areas of Wisconsin to recruit PWID 18-29 years who reported injection drug use in the previous 12 months. Participants were tested for HCV antibody (anti-HCV) and reported injection-related behaviors/practices via self-administered computer-based survey. We calculated anti-HCV prevalence and assessed associated factors using multivariable logistic regression. RESULTS: Forty-two percent (117/280) of participants were male, 83% (231/280) were white, and median age was 23 years. Overall HCV prevalence was 33%, but HCV prevalence among males was 39%. Adjusting for age, sex, race/ethnicity, education, relationship status, insurance status and income, anti-HCV positivity was associated with higher injection frequency (> 100 times in the past six months) (aOR = 3.07; 95% Confidence Interval (95% CI): 1.72-5.45), ever shared syringes (aOR = 5.15; 95% CI: 2.52-10.51), past week/last use receptive rinse water sharing (aOR = 1.88; 95% CI: 1.06-3.33), past week/last use receptive filter sharing (aOR = 3.25; 95% CI: 1.61-6.54), reusing syringes (aOR = 1.91, 95% CI: 1.08-3.37), history of overdose (aOR = 8.82; 95% CI: 2.26-3.95), and having ever injected another PWID (aOR = 8.82; 95%CI 3.94-19.76). DISCUSSION: Anti-HCV positivity is associated with high-risk injection practices. Young PWID would benefit from access to evidence-based interventions that reduce their risk of infection, link those infected to HCV treatment, and provide education to reduce further transmission.

    • Veterinary Medicine
      1. Coxiella burnetii is an intracellular bacterial pathogen that can be associated with significant reproductive disease or acute mortality in livestock and wildlife. A novel marine mammal-associated strain of C. burnetii has been identified in pinnipeds of the Northwestern Pacific Ocean. Little is known about C. burnetii infection in regard to reproductive success or population status. Our objective was to characterize the severity and extent of histologic lesions in 117 opportunistically collected placentas from presumed-normal northern fur seals (Callorhinus ursinus) in July 2011 on St. Paul Island, Alaska, where a high placental prevalence of C. burnetii had been reported. Sections were examined by histology and immunohistochemistry and impression smears with modified acid-fast stain. The nature and frequency of histologic changes were compared with target COM1 PCR-confirmed C. burnetii positive and negative placentas. Overall, histologic changes were similar to placental lesions described in aborting ruminants; however, changes were variable within and between placentas. Vasculitis and occasional intracellular bacteria were seen only in C. burnetii PCR-positive placentas. Dystrophic mineralization, edema, and inflammation were seen in PCR-positive and negative placentas, although they were statistically more common in PCR-positive placentas. Results suggest that C. burnetti and associated pathologic changes are multifocal and variable in placentas from these presumably live-born pups. Therefore, multiple sections of tissue from different placental areas should be examined microscopically and screened by PCR to ensure accurate diagnosis, as the genomes per gram of placenta may not necessarily represent the severity of placental disease. These limitations should inform field biologists, diagnosticians, and pathologists how best to screen and sample for pathogens and histopathology in marine mammal placental samples.

    • Zoonotic and Vectorborne Diseases
      1. Knowledge, attitudes, and behaviors regarding tick-borne disease prevention in Lyme disease-endemic areas of the Upper Midwest, United Statesexternal icon
        Beck A, Bjork J, Biggerstaff BJ, Eisen L, Eisen R, Foster E, Signs K, Tsao JI, Kough E, Peterson M, Schiffman E, Muganda CP, Osborn R, Wozniak R, Bron GM, Phaneuf D, Smith D, Bartholomay L, Paskewitz S, Hinckley AF.
        Ticks Tick Borne Dis. 2022 Feb 19;13(3):101925.
        Lyme disease and other tick-borne diseases are a major public health threat in the Upper Midwestern United States, including Michigan, Minnesota, and Wisconsin. To prevent tick bites and tick-borne diseases, public health officials commonly recommend personal protective measures and property management techniques. Adoption of tick-borne disease prevention behaviors and practices by individuals are, however, highly variable. We aimed to characterize current tick-borne disease knowledge, attitudes, and prevention behaviors (KAB) practiced by the public in these states, as well as their willingness to use specific tick control methods. We conducted a population-based survey in summer 2019 in 48 high-risk counties (those having a five-year average (2013-2017) Lyme disease incidence of ≥ 10 cases per 100,000 persons per year), in Michigan, Minnesota, and Wisconsin. A total of 2713 surveys were analyzed; survey weights were used to account for household selection probability and post-stratified to match county-level joint age and sex population distributions in population-level inference. An estimated 98% of the population had heard of Lyme disease, with most perceiving it as very or extremely serious (91%); however, only an estimated 25% perceived tick-borne diseases as very or extremely common in their community. Among those who spent time in places with ticks from April through October, an estimated 68% check themselves thoroughly for ticks most of the time or always and 43% use bug repellent on skin or clothing most of the time or always. An estimated 13% of the population had ever treated their property with a pesticide to kill ticks, and 3% had ever used devices that apply pesticide to rodents to kill ticks on their property. Willingness to practice tick bite prevention behaviors, however, was estimated to be much higher; with 82% being willing to perform tick checks at least once a day, and more than 60% willing to use bug repellent, tick control products on pets, or to bathe within two hours of being outdoors. We found that residents would likely be willing to support a county-wide tick control program to reduce the risk of tick-borne disease in their community (81%) or to apply tick control products to their property to reduce the risk of tick-borne disease in their household (79%). Tick checks were more likely to be practiced among participants who perceived tick-borne diseases to be highly prevalent in their community, if they or a household member had been previously diagnosed with a tick-borne disease?, or if they perceived tick exposure to be likely around their home, cabin, or vacation home. In addition, property-based tick control methods were associated with perceived risk of encountering ticks around the home, cabin, or vacation home. Participants who had seen information from state health departments were also more likely to practice preventive measures. The most common reported barriers to using any of these methods were forgetfulness, safety concerns, and lack of awareness. Our survey findings shed light on how residents from these Upper Midwest states may adopt tick control and tick bite prevention measures and how public health outreach may be most effective for this population.

      2. Anaplasmosis-related fatality in Vermont: A case reportexternal icon
        Leikauskas JA, Read JS, Kelso P, Nichols Heitman K, Armstrong PA, Kwit NA.
        Vector Borne Zoonotic Dis. 2022 Mar 9.
        Human granulocytic anaplasmosis is an acute febrile tick-borne illness caused by the bacterium Anaplasma phagocytophilum. An anaplasmosis-related fatality in a Vermont resident with multiple comorbidities is described. Clinicians should be aware of the risk factors for severe outcomes of this emerging disease and promptly treat when suspected.

      3. Potential quantitative effect of a laboratory-based approach to Lyme disease surveillance in high-incidence statesexternal icon
        Kugeler KJ, Cervantes K, Brown CM, Horiuchi K, Schiffman E, Lind L, Barkley J, Broyhill J, Murphy J, Crum D, Robinson S, Kwit NA, Mullins J, Sun J, Hinckley AF.
        Zoonoses Public Health. 2022 Mar 6.
        Historically, public health surveillance for Lyme disease has required clinical follow-up on positive laboratory reports for the purpose of case classification. In areas with sustained high incidence of the disease, this resource-intensive activity yields a limited benefit to public health practice. A range of burden-reducing strategies have been implemented in many states, creating inconsistencies that limit the ability to decipher trends. Laboratory-based surveillance, or surveillance based solely on positive laboratory reports without follow-up for clinical information on positive laboratory reports, emerged as a feasible alternative to improve standardization in already high-incidence areas. To inform expectations of a laboratory-based surveillance model, we conducted a retrospective analysis of Lyme disease data collected during 2012-2018 from 10 high-incidence states. The number of individuals with laboratory evidence of infection ranged from 1302 to 20,994 per state and year. On average, 55% of those were ultimately classified as confirmed or probable cases (range: 29%-86%). Among all individuals with positive laboratory evidence, 18% (range: 2%-37%) were determined to be 'not a case' upon investigation and 23% (range: 2%-52%) were classified as suspect cases due to lack of associated clinical information and thus were not reported to the Centers for Disease Control and Prevention (CDC). The number of reported cases under a laboratory-based approach to surveillance in high-incidence states using recommended two-tier testing algorithms is likely to be, on average, 1.2 times higher (range: 0.6-1.8 times) than what was reported to CDC during 2012-2018. A laboratory-based surveillance approach for high-incidence states will improve standardization and reduce burden on public health systems, allowing public health resources to focus on prevention messaging, exploration of novel prevention strategies and alternative data sources to yield information on the epidemiology of Lyme disease.

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