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Issue 15, April 11, 2023

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CDC Science Clips: Volume 15, Issue 15, April 11, 2023

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

The report consists of these components:

  1. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. First known report of mcr-harboring enterobacteriaceae in the Dominican Republic
        Perdomo A, Webb HE, Bugarel M, Friedman CR, Francois Watkins LK, Loneragan GH, Calle A.
        Int J Environ Res Public Health. 2023 ;20(6).
        Colistin is a last-resort antibiotic used to treat infections caused by multidrug-resistant Gram-negative bacteria. People with a history of travel to the Dominican Republic have become sick with pathogenic bacteria carrying the mobile colistin resistance gene, mcr-1, during and after traveling. This investigation aimed to identify mcr genes in Enterobacteriaceae isolated from food animal sources in the Dominican Republic. Three hundred and eleven samples were tested, from which 1354 bacterial isolates were obtained. Real-time PCR tests showed that 70.7% (220 out of 311) of the samples and 3.2% (44 out of 1354) of the isolates tested positive for the mcr gene. All RT-PCR presumptive mcr-positive isolates (n = 44) and a subset (n = 133) of RT-PCR presumptive mcr-negative isolates were subjected to whole-genome sequencing. WGS analysis showed that 39 isolates carried the mcr gene, with 37 confirmed as positive through RT-PCR and two as negative. Further, all of the mcr-positive genomes were identified as Escherichia coli and all contained a IncX4 plasmid replicon. Resistant determinants for other antibiotics important for human health were found in almost all isolates carrying mcr genes.

        Webb, H. E. Friedman, C. R. Francois Watkins, L. K.

    • Chronic Diseases and Conditions
      1. PURPOSE: We assessed an educational intervention to reduce the number of emergency department (ED) and inpatient stays for cardiovascular diagnoses, among South Carolina adult Medicaid Members with intellectual and developmental disability and hypertension (Members). DESIGN: This Randomized Controlled Trial (RCT) included Members or the person who helped them with their medications (Helpers). Participants, who included Members and/or their Helpers, were randomly assigned to an Intervention or Control group. SETTING: South Carolina Department of Health and Human Services, which administers Medicaid, identified eligible Members. SAMPLE: 412 Medicaid Members - 214 Intervention (54 Members participating directly; 160 Helpers participating in lieu of Members) who received the messages about hypertension and surveys about knowledge and behavior and 198 Controls (62 Members; 136 Helpers) who only received surveys of knowledge and behavior. INTERVENTION: Educational intervention about hypertension included a flyer and monthly text or phone messages for one year. MEASURES: Input measures - characteristics of the Members; Outcome measures - hospital emergency department (ED) and inpatient visits for cardiovascular conditions. ANALYSIS: Quantile regression tested the association of Intervention/Control group status with ED and inpatient visits. We also estimated models using Zero-inflated Poisson (ZIP) models for sensitivity analysis. RESULTS: Participants in the Intervention group with highest baseline hospital use (top 20% ED; top 15% Inpatient) had significant reductions in Year 1 (.57 fewer ED and 2 fewer inpatient days) compared to the Control group. For ED visits, improvement continued in year two. CONCLUSION: The intervention reduced the frequency of cardiovascular disease-related ED visits and Inpatient days for participants in the Intervention group in the highest quantiles of hospital use, and the improvement was better for those who had a Helper.

        Hollis, N. D.

      2. Clinical characteristics of children with Tourette syndrome with and without sleep disorder
        Ricketts EJ, Wolicki SB, Holbrook JR, Rozenman M, McGuire JF, Charania SN, Piacentini J, Mink JW, Walkup JT, Woods DW, Claussen AH.
        Pediatr Neurol. 2023 ;141:18-24.
        BACKGROUND: Sleep problems are common in children with Tourette Syndrome (TS). However, research regarding their demographic and clinical profile is limited. METHODS: We examined characteristics of 114 children aged five to 17 years with a lifetime diagnosis of TS and compared children with sleep disorder (n = 32) and without sleep disorder (n = 82). Parent report from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome provided demographics and clinical information, other diagnosed disorders, medication use, TS severity, and impairment. RESULTS: More children with TS with sleep disorder were from households with lower parental education (P < 0.01) and poverty (P = 0.04); had other diagnoses (P = 0.03), including obsessive-compulsive disorder (P < 0.01), oppositional defiant disorder or conduct disorder (P < 0.01), attention-deficit/hyperactivity disorder (ADHD) (P = 0.02), and autism (P = 0.03); and had ever used TS medication (P = 0.01) than children with TS without sleep disorder. More children with TS with sleep disorder had severe TS symptoms (P <0.01), tic-related impairment (P<0.01), and severe ADHD symptoms (P < 0.01) compared with children with TS without sleep disorder. CONCLUSIONS: Findings suggest greater parent-reported impact and tic-related interference in children with TS with sleep disorder compared with TS without sleep disorder. Results underscore the importance of monitoring and intervention for TS exacerbations, other diagnosed disorders, and medication use, and consideration of socioeconomic context in sleep disorder management and prevention in children with TS.

        Wolicki, S. B. Holbrook, J. R. Charania, S. N.

    • Communicable Diseases
      1. Linkage to HIV care and early retention in care rates in the universal test-and-treat era: A population-based prospective study in KwaZulu-Natal, South Africa
        Nicol E, Basera W, Mukumbang FC, Cheyip M, Mthethwa S, Lombard C, Jama N, Pass D, Laubscher R, Bradshaw D.
        AIDS Behav. 2023 ;27(4):1068-1081.
        HIV linkage, and retention are key weaknesses in South Africa's national antiretroviral therapy (ART) program, with the greatest loss of patients in the HIV treatment pathway occurring before ART initiation. This study investigated linkage-to and early-retention-in-care (LTRIC) rates among adults newly diagnosed with HIV in a high-HIV prevalent rural district. We conducted an observational prospective cohort study to investigate LTRIC rates for adults with a new HIV diagnosis in South Africa. Patient-level survey and clinical data were collected using a one-stage-cluster design from 18 healthcare facilities and triangulated between HIV and laboratory databases and registered deaths from Department of Home Affairs. We used Chi-square tests to assess associations between categorical variables, and results were stratified by HIV status, sex, and age. Of the 5,637 participants recruited, 21.2% had confirmed HIV, of which 70.9% were women, and 46.5% were aged 25-34 years. Although 82.7% of participants were linked-to-care within 3 months, only 46.1% remained-in-care 12 months after initiating ART and 5.2% were deceased. While a significantly higher proportion of men were linked-to-care at 3 months compared to women, a significant proportion of women (49.5%) remained-in-care at 12 months than men (38.0%). Post-secondary education and child support grants were significantly associated with retention. We found high linkage-to-care rates, but less than 50% of participants remained-in-care at 12 months. Significant effort is required to retain people living with HIV in care, especially during the first year after ART initiation. Our findings suggest that interventions could target men to encourage HIV testing.

        Cheyip, M. Mthethwa, S.

      2. Evaluation of correctional facility COVID-19 outbreaks with layered mitigation strategies including vaccination: Colorado, 2020-2021
        Martinez HE, Marshall KE, Showell VW, Tate JE, Kirking HL, Broudy M, Matzinger SR, Burakoff A, Deng L, Payne DC, Fleming-Dutra K, Jervis RH.
        J Correct Health Care. 2023 .
        In 2020-2021, a Colorado corrections facility experienced four COVID-19 outbreaks. Case counts, attack rates (ARs) in people who are detained or incarcerated (PDI), and mitigation measures used in each outbreak were compared to evaluate effects of combined strategies. Serial PCR testing, isolation/quarantine, and masking were implemented in outbreak 1. Daily staff antigen testing began in outbreak 2. Facility-wide COVID-19 vaccination started in outbreak 3 and coverage increased by the end of outbreak 4 (PDI: <1% to 59%, staff: 27% to 40%). Despite detection of variants of concern, outbreaks 3 and 4 had 97% lower PDI ARs (both 1%) than outbreak 2 (29%). Daily staff testing and increasing vaccination coverage, with other outbreak mitigation strategies, are important to reduce COVID-19 transmission in congregate settings.

        Marshall, K. E. Tate, J. E. Kirking, H. L. Deng, L. Payne, D. C. Fleming-Dutra, K.

      3. Vital Signs: Progress toward eliminating HIV as a global public health threat through scale-up of antiretroviral therapy and health system strengthening supported by the U.S. President's Emergency Plan for AIDS Relief - Worldwide, 2004-2022
        Chun HM, Dirlikov E, Cox MH, Sherlock MW, Obeng-Aduasare Y, Sato K, Voetsch AC, Ater AD, Romano ER, Tomlinson H, Modi S, Achrekar A, Nkengasong J.
        MMWR Morb Mortal Wkly Rep. 2023 ;72(12):317-324.
        INTRODUCTION: In 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), with CDC as a major U.S. government implementing agency, began providing HIV antiretroviral therapy (ART) worldwide. Through suppression of HIV viral load, effective ART reduces morbidity and mortality among persons with HIV infection and prevents vertical and sexual transmission. METHODS: To describe program impact, data were analyzed from all PEPFAR programs and from six countries that have conducted nationally representative Population-based HIV Impact Assessment (PHIA) surveys, including PEPFAR programmatic data on the number of persons with HIV infection receiving PEPFAR-supported ART (2004-2022), rates of viral load coverage (the proportion of eligible persons with HIV infection who received a viral load test) and viral load suppression (proportion of persons who received a viral load test with <1,000 HIV copies per mL of blood) (2015-2022), and population viral load suppression rates in six countries that had two PHIA surveys conducted during 2015-2021. To assess health system strengthening, data on workforce and laboratory systems were analyzed. RESULTS: By September 2022, approximately 20 million persons with HIV infection in 54 countries were receiving PEPFAR-supported ART (62% CDC-supported); this number increased 300-fold from the 66,550 reported in September 2004. During 2015-2022, viral load coverage more than tripled, from 24% to 80%, and viral load suppression increased from 80% to 95%. Despite increases in viral load suppression rates and health system strengthening investments, variability exists in viral load coverage among some subpopulations (children aged <10 years, males, pregnant women, men who have sex with men [MSM], persons in prisons and other closed settings [persons in prisons], and transgender persons) and in viral load suppression among other subpopulations (pregnant and breastfeeding women, persons in prisons, and persons aged <20 years). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Since 2004, PEPFAR has scaled up effective ART to approximately 20 million persons with HIV infection in 54 countries. To eliminate HIV as a global public health threat, achievements must be sustained and expanded to reach all subpopulations. CDC and PEPFAR remain committed to tackling HIV while strengthening public health systems and global health security.

        Chun, H. M. Dirlikov, E. Cox, M. H. Sherlock, M. W. Obeng-Aduasare, Y. Sato, K. Voetsch, A. C. Ater, A. D. Romano, E. R. Tomlinson, H. Modi, S. Achrekar, A. Nkengasong, J.

      4. Retaining patients with drug-resistant tuberculosis on treatment during the COVID-19 pandemic - Dharavi, Mumbai, India, 2020-2022
        Gomare MD, Bhide S, Deshmukh R, Kaipilyawar S, Puri V, Moonan PK, Khetade DK, Nyendak M, Yeldandi V, Smith JP, Tobias JL, Date A, Joshi R, Kumar R, Ho CS.
        MMWR Morb Mortal Wkly Rep. 2023 ;72(12):304-308.
        Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum(†); historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies.

        Deshmukh, R. Moonan, P. K. Nyendak, M. Smith, J. P. Tobias, J. L. Date, A. Ho, C. S.

      5. Tuberculosis - United States, 2022
        Schildknecht KR, Pratt RH, Feng PI, Price SF, Self JL.
        MMWR Morb Mortal Wkly Rep. 2023 ;72(12):297-303.
        Incidence of reported tuberculosis (TB) decreased gradually in the United States during 1993-2019, reaching 2.7 cases per 100,000 persons in 2019. Incidence substantially declined in 2020 to 2.2, coinciding with the COVID-19 pandemic (1). Proposed explanations for the decline include delayed or missed TB diagnoses, changes in migration and travel, and mortality among persons susceptible to TB reactivation (1). Disparities (e.g., by race and ethnicity) in TB incidence have been described (2). During 2021, TB incidence partially rebounded (to 2.4) but remained substantially below that during prepandemic years, raising concerns about ongoing delayed diagnoses (1). During 2022, the 50 U.S. states and the District of Columbia (DC) provisionally reported 8,300 TB cases to the National Tuberculosis Surveillance System. TB incidence was calculated using midyear population estimates and stratified by birth origin and by race and ethnicity. During 2022, TB incidence increased slightly to 2.5 although it remained lower than during prepandemic years.* Compared with that in 2021, TB epidemiology in 2022 was characterized by more cases among non-U.S.-born persons newly arrived in the United States; higher TB incidence among non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons and persons aged ≤4 and 15-24 years; and slightly lower incidence among persons aged ≥65 years. TB incidence appears to be returning to prepandemic levels. TB disparities persist; addressing these disparities requires timely TB diagnosis and treatment to interrupt transmission and prevention of TB through treatment of latent TB infection (LTBI).

        Schildknecht, K. R. Pratt, R. H. Feng, P. I. Price, S. F. Self, J. L.

      6. Tuberculosis outbreak in a state prison system - Washington, 2021-2022
        Stalter RM, Pecha M, Dov L, Miller D, Ghazal Z, Wortham J, Althomsons S, Deutsch-Feldman M, Stewart R, Felix D, Hsu S, Strick LB.
        MMWR Morb Mortal Wkly Rep. 2023 ;72(12):309-312.
        During 2014-2020, no tuberculosis (TB) cases were reported within the Washington state prison system. However, during July 2021-June 2022, 25 TB cases were reported among persons incarcerated or formerly incarcerated in two Washington state prisons. Phylogenetic analyses of whole genome sequencing data indicated that Mycobacterium tuberculosis isolates from all 11 patients with culture-confirmed TB were closely related, suggesting that these cases represented a single outbreak. The median infectious period for 12 patients who were considered likely contagious was 170 days. As of November 15, 2022, the Washington State Department of Corrections (WADOC) and Washington State Department of Health (WADOH), with technical assistance from CDC, had identified 3,075 contacts among incarcerated residents and staff members at five state prisons, and 244 contacts without a known TB history received a diagnosis of latent TB infection (LTBI). Persons who were evaluated for TB disease were isolated; those receiving a diagnosis of TB then initiated antituberculosis therapy. Persons with LTBI were offered treatment to prevent progression to TB disease. This ongoing TB outbreak is the largest in Washington in 20 years. Suspension of annual TB screening while limited resources were redirected toward the COVID-19 response resulted in delayed case detection that facilitated TB transmission. In addition, fear of isolation might discourage residents and staff members from reporting symptoms, which likely also leads to delayed TB diagnoses. Continued close collaboration between WADOC and WADOH is needed to end this outbreak and prevent future outbreaks.

        Wortham, J. Althomsons, S. Deutsch-Feldman, M. Stewart, R. Felix, D. Hsu, S.

      7. Use of severe acute respiratory syndrome coronavirus 2 antibody tests by US infectious disease physicians: Results of an emerging infections network survey, March 2022
        Gundlapalli AV, Beekmann SE, Jones JM, Thornburg NJ, Clarke KE, Uyeki TM, Satheshkumar PS, Carroll DS, Plumb ID, Briggs-Hagen M, Santibañez S, David-Ferdon C, Polgreen PM, McDonald LC.
        Open Forum Infect Dis. 2023 ;10(3):ofad091.
        BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. METHODS: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. RESULTS: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. CONCLUSIONS: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance.

        Gundlapalli, A. V. Jones, J. M. Thornburg, N. J. Clarke, K. E. N. Uyeki, T. M. Satheshkumar, P. S. Carroll, D. S. Plumb, I. D. Briggs-Hagen, M. Santibañez, S. David-Ferdon, C. McDonald, L. C.

      8. COVID-19 outbreaks in congregate settings remain a serious threat to the health of disproportionately affected populations such as people experiencing incarceration or homelessness, the elderly, and essential workers. An individual-based model accounting for individual infectiousness over time, staff work schedules, and testing and isolation schedules was developed to simulate community transmission of SARS-CoV-2 to staff in a congregate facility and subsequent transmission within the facility that could cause an outbreak. Systematic testing strategies in which staff are tested on the first day of their workweek were found to prevent up to 16% more infections than testing strategies unrelated to staff schedules. Testing staff at the beginning of their workweek, implementing timely isolation following testing, limiting test turnaround time, and increasing test frequency in high transmission scenarios can supplement additional mitigation measures to aid outbreak prevention in congregate settings.

        Skaff, N. K. Fukunaga, R.

      9. Antiretroviral treatment failure and associated factors among people living with HIV on therapy in Homa Bay, Kenya: A retrospective study
        Masaba R, Woelk G, Siamba S, Ndimbii J, Ouma M, Khaoya J, Kipchirchir A, Ochanda B, Okomo G.
        PLOS Glob Public Health. 2023 ;3(3):e0001007.
        Despite large numbers of patients accessing antiretroviral treatment (ART) in Kenya, few studies have explored factors associated with virologic failure in Western Kenya, specifically. We undertook a study in Homa Bay County, Kenya to assess the extent of virologic treatment failure and factors associated with it. This was an observational retrospective study conducted from September 2020 to January 2021. Data were abstracted from the records of patients who had been on ART for at least six months at the time of data collection after systematic sampling stratified by age group at ART initiation (0-14 and 15+ years), using probability proportion to the numbers of patients attending the facility. Confirmed viral treatment failure was defined as viral load ≥1000 copies/ml based on two consecutive viral load measurements after at least three months of enhanced adherence counseling. Data were analyzed using descriptive statistics and Cox regression modeling. Of the 2,007 patients sampled, 160 (8.0%) had confirmed virologic treatment failure. Significantly higher virologic treatment failure rates were identified among male patients 78/830 (9.4%) and children 115/782 (14.7%). Factors associated with virologic treatment failure (VTF), were age 0-14 years, adjusted hazard ratio (AHR) 4.42, (95% Confidence Interval [CI], 3.12, 6.32), experience of treatment side effects AHD: 2.43, (95% CI, 1.76, 3.37), attending level 2/3 health facility, AHR: 1.87, (95% CI: 1.29, 2,72), and history of opportunistic infections (OIs), AHR: 1.81, (95% CI, 1.76, 3.37). Children, attendees of level 2/3 health facilities, patients with a history of OIs, and those experiencing treatment side-effects are at risk of VTF. Increased focus on children and adolescents on screening for drug resistance, administration of and adherence to medication, and on effective information and education on side-effects is critical. Additionally, there is need for increased training and support for health care workers at primary level care facilities.

        Ochanda, B.

      10. A multicenter survey of asymptomatic cryptococcal antigenemia among patients with advanced HIV disease in Nigeria
        Oladele RO, Jordan AM, Okaa JU, Osaigbovo , Shettima SA, Shehu NY, Davies AA, Mohammed Y, Alex-Wele MA, Iliyasu G, Nwaokenye JC, Fayemiwo SA, Udoh UA, Gbajabiamila T, Denning DW, Chiller TM.
        PLOS Glob Public Health. 2023 ;3(1):e0001313.
        As of 2018, cryptococcal antigen (CrAg) screening in patients with advanced human immunodeficiency virus (HIV) disease (AHD) was not routinely implemented in Nigeria despite being recommended in the national HIV treatment guidelines. Our aim was to determine the prevalence and risk factors for asymptomatic cryptococcal antigenemia in adult people living with HIV (PLHIV) in Nigeria to advocate for the implementation of routine CrAg screening. A descriptive cross-sectional study and CrAg screening of consecutive adult PLHIV with CD4 counts ≤200 cells/μL was conducted from April 2018 to April 2019 at HIV clinics in eleven tertiary hospitals spread across Nigeria's six geopolitical regions. Prevalence of asymptomatic cryptococcal antigenemia was estimated by facility and geopolitical zone. Logistic regression was conducted to identify risk factors for cryptococcal antigenemia. In total, 1,114 patients with AHD were screened. The overall prevalence of asymptomatic cryptococcal antigenemia was 3.9% with wide variation across facilities (range: 0/75 [0%]- 15/122 [12.3%]) and geopolitical zones (range: 0/75 [0%]-19/279 [6.8%]). Prevalence of antigenemia was highest in the South-West (19/279 [6.8%]) and lowest in the North-East (0/75 [0%]). Prevalence was 5.2% (26/512) and 3.2% (18/561) in patients with CD4<100 and CD4 of 101-200, respectively. Of all patients with antigenemia, 50% were on antiretroviral therapy (ART) at the time of having a positive CrAg test. In adjusted analysis, cryptococcal antigenemia was significantly less in patients on ART and patients who had completed any formal education. The survey showed a high overall burden of cryptococcal antigenemia in Nigeria, with variable prevalence across geopolitical regions. We provided valuable evidence for implementing routine CrAg screening of AHD patients in Nigeria which has commenced in selected centres.

        Jordan, A. M. Chiller, T. M.

      11. The future of HIV testing in eastern and southern Africa: Broader scope, targeted services
        Grimsrud A, Wilkinson L, Ehrenkranz P, Behel S, Chidarikire T, Chisenga T, Golin R, Johnson CC, Milanga M, Onyekwena O, Sundaram M, Wong V, Baggaley R.
        PLoS Med. 2023 ;20(3):e1004182.
        In this Policy Forum, Anna Grimsrud and colleagues discuss the future of HIV testing in eastern and southern Africa, using insights gleaned from a 2021 expert consultation.

        Behel, S.

    • Community Health Services
      1. Recommendations for use of video directly observed therapy during tuberculosis treatment - United States, 2023
        Mangan JM, Woodruff RS, Winston CA, Nabity SA, Haddad MB, Dixon MG, Parvez FM, Sera-Josef C, Salmon-Trejo LA, Lam CK.
        MMWR Morb Mortal Wkly Rep. 2023 ;72(12):313-316.
        U.S. clinical practice guidelines recommend directly observed therapy (DOT) as the standard of care for tuberculosis (TB) treatment (1). DOT, during which a health care worker observes a patient ingesting the TB medications, has typically been conducted in person. Video DOT (vDOT) uses video-enabled devices to facilitate remote interactions between patients and health care workers to promote medication adherence and clinical monitoring. Published systematic reviews, a published meta-analysis, and a literature search through 2022 demonstrate that vDOT is associated with a higher proportion of medication doses being observed and similar proportions of cases with treatment completion and microbiologic resolution when compared with in-person DOT (2-5). Based on this evidence, CDC has updated the recommendation for DOT during TB treatment to include vDOT as an equivalent alternative to in-person DOT. vDOT can assist health department TB programs meet the U.S. standard of care for patients undergoing TB treatment, while using resources efficiently.

        Mangan, J. M. Woodruff, R. S. Winston, C. A. Nabity, S. A. Haddad, M. B. Dixon, M. G. Parvez, F. M. Sera-Josef, C. Salmon-Trejo, L. A. T. Lam, C. K.

    • Disaster Preparedness and Emergency Services
      1. Uganda's experience in establishing an electronic compendium for public health emergencies
        Ario AR, Aliddeki DM, Kadobera D, Bulage L, Kayiwa J, Wetaka MM, Kyazze S, Ocom F, Makumbi I, Mbaka P, Behumbiize P, Ayebazibwe I, Balinandi SK, Lutwama JJ, Crawley A, Divi N, Lule JR, Ojwang JC, Harris JR, Boore AL, Nelson LJ, Borchert J, Jarvis D.
        PLOS Glob Public Health. 2023 ;3(2):e0001402.
        Uganda has implemented several interventions that have contributed to prevention, early detection, and effective response to Public Health Emergencies (PHEs). However, there are gaps in collecting and documenting data on the overall response to these PHEs. We set out to establish a comprehensive electronic database of PHEs that occurred in Uganda since 2000. We constituted a core development team, developed a data dictionary, and worked with Health Information Systems Program (HISP)-Uganda to develop and customize a compendium of PHEs using the electronic Integrated Disease Surveillance and Response (eIDSR) module on the District Health Information Software version 2 (DHIS2) platform. We reviewed literature for retrospective data on PHEs for the compendium. Working with the Uganda Public Health Emergency Operations Center (PHEOC), we prospectively updated the compendium with real-time data on reported PHEs. We developed a user's guide to support future data entry teams. An operational compendium was developed within the eIDSR module of the DHIS2 platform. The variables for PHEs data collection include those that identify the type, location, nature and time to response of each PHE. The compendium has been updated with retrospective PHE data and real-time prospective data collection is ongoing. Data within this compendium is being used to generate information that can guide future outbreak response and management. The compendium development highlights the importance of documenting outbreak detection and response data in a central location for future reference. This data provides an opportunity to evaluate and inform improvements in PHEs response.

        Lule, J. R. Ojwang, J. C. Harris, J. R. Boore, A. L. Nelson, L. J. Borchert, J. Jarvis, D.

    • Disease Reservoirs and Vectors
      1. Geographic information system protocol for mapping areas targeted for mosquito control in North Carolina
        Mueller A, Thomas A, Brown J, Young A, Smith K, Connelly R, Richards SL.
        PLoS One. 2023 ;18(3):e0278253.
        Geographic information systems (GIS) can be used to map mosquito larval and adult habitats and human populations at risk for mosquito exposure and possible arbovirus transmission. Along with traditional methods of surveillance-based targeted mosquito control, GIS can help simplify and target efforts during routine surveillance and post-disaster (e.g., hurricane-related flooding) to protect emergency workers and public health. A practical method for prioritizing areas for emergency mosquito control has been developed and is described here. North Carolina (NC) One Map was used to identify state-level data layers of interest based on human population distribution and mosquito habitat in Brunswick, Columbus, Onslow, and Robeson Counties in eastern NC. Relevant data layers were included to create mosquito control treatment areas for targeted control and an 18-step protocol for map development is discussed. This protocol is expected to help state, territorial, tribal, and/or local public health officials and associated mosquito control programs efficiently create treatment area maps to improve strategic planning in advance of a disaster. This protocol may be applied to any NC county and beyond, thereby increasing local disaster preparedness.

        Connelly, R.

    • Environmental Health
      1. Case of primary amebic meningoencephalitis associated with surfing at an artificial surf venue: Environmental investigation
        Miko S, Cope JR, Hlavsa MC, Ali IK, Brown TW, Collins JP, Greeley RD, Kahler AM, Moore KO, Roundtree AV, Roy S, Sanders LL, Shah V, Stuteville HD, Mattioli MC.
        ACS ES T Water. 2022 .
        Naegleria fowleri is a thermophilic ameba found in freshwater that causes primary amebic meningoencephalitis (PAM) when it enters the nose and migrates to the brain. In September 2018, a 29-year-old man died of PAM after traveling to Texas. We conducted an epidemiologic and environmental investigation to identify the water exposure associated with this PAM case. The patient’s most probable water exposure occurred while surfing in an artificial surf venue. The surf venue water was not filtered or recirculated; water disinfection and water quality testing were not documented. N. fowleri and thermophilic amebae were detected in recreational water and sediment samples throughout the facility. Codes and standards for treated recreational water venues open to the public could be developed to address these novel venues. Clinicians and public health officials should also consider novel recreational water venues as a potential exposure for this rare amebic infection. Not subject to U.S. Copyright. Published 2023 by American Chemical Society.

        Miko, S. Cope, J. R. Hlavsa, M. C. Ali, I. K. M. Brown, T. W. Collins, J. P. Kahler, A. M. Roundtree, A. V. Mattioli, M. C.

      2. A prospective nested case-control study of serum concentrations of per- and polyfluoroalkyl substances and aggressive prostate cancer risk
        Rhee J, Barry KH, Huang WY, Sampson JN, Hofmann JN, Silverman DT, Calafat AM, Botelho JC, Kato K, Purdue MP, Berndt SI.
        Environ Res. 2023 :115718.
        Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested an association between PFAS and prostate cancer, but evidence from population-based studies is limited. We investigated the association between pre-diagnostic serum PFAS concentrations and aggressive prostate cancer risk in a large prospective study. We measured pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoate (PFOA), for 750 aggressive prostate cancer cases and 750 individually matched controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We assessed the reproducibility of PFAS concentrations in serial samples collected up to six years apart among 60 controls using intraclass correlation coefficients (ICCs). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with prostate cancer, adjusting for other PFAS and potential confounders. Concentrations of most PFAS were consistent (ICC>0.7) across the serial samples over time. We observed an inverse association between PFOA and aggressive prostate cancer (OR(continuous) = 0.79, 95% CI = 0.63, 0.99), but the association was limited to cases diagnosed ≤3 years after blood collection and became statistically non-significant for cases diagnosed with later follow-up (>3 years, OR(continuous) = 0.90, 95% CI = 0.79, 1.03). Other PFAS were not associated with aggressive prostate cancer risk. Although we cannot rule out an increased risk at higher levels, our findings from a population with PFAS serum concentrations comparable to the general population do not support an association with increased risk of aggressive prostate cancer.

        Botelho, J. C. Kato, K.

      3. BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large group of chemicals that have been integrated into a wide variety of industrial processes and consumer products since the 1950s. Due to their profuse usage and high persistence in human serum, understanding workplace exposures to PFAS is critical. OBJECTIVE: We aimed to characterize the PFAS exposure profiles of relevant occupational populations, elucidate trends in the PFAS exposure characterization process, and identify major research gaps that remain within the occupational PFAS exposure literature. METHODS: A systematic search of four literature databases for peer-reviewed articles published between 1980 and 2021 on PFAS exposure in occupational settings was conducted. RESULTS: Of the 2574 articles identified, 92 met the inclusion criteria. Fluorochemical workers were the target population in most early exposure assessment research; however, studies conducted within the last 10 years have evaluated a wider range of occupational populations and settings. The highest exposures were reported in fluorochemical workers, but, in comparison to reference populations, one or more PFAS were elevated in most workers and in most workplaces that were assessed. PFAS was most frequently assessed in worker serum using a discrete analytical panel of PFAS, with earlier studies restricted to a few long-alkyl chain PFAS while more recent studies have included more expansive panels due to more robust methods. SIGNIFICANCE: Characterization of occupational exposure to PFAS is limited but expanding. Current analytical methods are not robust enough to fully capture the potential range of PFAS present across different workers and workplaces. While exposures to PFAS for certain occupational groups have been studied in detail, exposure information for other occupational groups with high potential for exposure are limited. This review highlights substantial findings and major research gaps within the occupational literature.

        Christensen, B. T. Calkins, M. M.

      4. Legionnaires' disease outbreak associated with a hot tub display at the North Carolina Mountain State Fair, September 2019
        Donovan CV, MacFarquhar JK, Wilson E, Sredl M, Tanz LJ, Mullendore J, Fleischauer A, Smith JC, Lucas C, Kunz J, Moore Z.
        Public Health Rep. 2023 :333549231159159.
        OBJECTIVES: On September 23, 2019, the North Carolina Division of Public Health identified a legionellosis increase in western North Carolina; most patients had recently attended the North Carolina Mountain State Fair. We conducted a source investigation. METHODS: Cases were fair attendees with laboratory-confirmed legionellosis and symptom onset within 2 to 14 days (Legionnaires' disease) or ≤3 days (Pontiac fever). We conducted a case-control study matching cases to non-ill fair attendees as control participants and an environmental investigation, and we performed laboratory testing (Legionella bacteria culture and polymerase chain reaction) of 27 environmental samples from fairgrounds and hot tubs and 14 specimens from case patients. We used multivariable unconditional logistic regression models to calculate adjusted odds ratios for potential Legionella exposure sources and risk factors. RESULTS: Of 136 people identified with fair-associated legionellosis, 98 (72%) were hospitalized and 4 (3%) died. Case patients were more likely than control participants to report walking by hot tub displays (adjusted odds ratio = 10.0; 95% CI, 4.2-24.1). Complete hot tub water treatment records were not kept, precluding evaluation of water maintenance conducted on display hot tubs. Legionella pneumophila sequence types (STs) were consistent among 10 typed clinical specimens (ST224) but distinct from the only positive environmental sample from the fair (ST7 and ST8). CONCLUSIONS: Hot tub displays were identified as the most likely outbreak source, making this the largest hot tub-associated Legionnaires' disease outbreak worldwide. Following the investigation, the North Carolina Division of Public Health and the Centers for Disease Control and Prevention released guidance on mitigating risk of Legionella exposure from hot tub displays. Results highlight the importance of properly maintaining equipment that aerosolizes water, including hot tubs intended for display purposes only.

        Donovan, C. V. MacFarquhar, J. K. Tanz, L. J. Smith, J. C. Lucas, C. Kunz, J.

      5. The U.S. National Council on Radiation Protection and Measurements (NCRP) conducted a retrospective assessment of the U.S. data, and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) performed a similar worldwide assessment for 2009-2018 (with most data from 2014 to 2017). Using the data from those reports, the frequency of radiologic and nuclear medicine studies, annual collective, and per capita effective dose in the United States for 2016 were compared with worldwide estimates from 2009 to 2018. There were an estimated 691 million radiologic, CT, dental, and nuclear medicine studies performed in the United States in 2016, which represented 16.5% of the 4.2 billion performed worldwide. The United States also accounted for 74 million CT procedures (18% of the world's estimated total), 275 million conventional radiology procedures (11% of the world's total), 8.1 million interventional radiologic procedures (34% of the world's total), 320 million dental radiography procedures (29% of the world's total), and 13.5 million nuclear medicine procedures (34% of the world's total). The U.S. collective effective dose was 717 000 person-sieverts (17.6% of the world's total). The average annual individual effective dose in the United States was 2.2 mSv compared with 0.56 mSv worldwide. The United States accounts for a large and disproportionate share of global medical radiation procedures and collective effective dose, but use of CT has increased more in other countries compared with the United States.

        Ansari, A. J.

    • Epidemiology and Surveillance
      1. Sensitivity and uncertainty analysis for two-stream capture-recapture methods in disease surveillance
        Zhang Y, Chen J, Ge L, Williamson JM, Waller LA, Lyles RH.
        Epidemiology. 2023 .
        Capture-recapture methods are widely applied in estimating the number (N) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are two data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically non-identifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist's understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of N. By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is a simulation-based approach designed to more realistically acknowledge variability in the estimated N associated with uncertainty in an expert's opinion about the non-identifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture-recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating N in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from more than two surveillance streams.

        Williamson, J. M.

      2. Population size estimation of men who have sex with men in Rwanda: Three-source capture-recapture method
        Tuyishime E, Kayitesi C, Musengimana G, Malamba S, Moges H, Kankindi I, Escudero HR, Habimana Kabano I, Oluoch T, Remera E, Chukwu A.
        JMIR Public Health Surveill. 2023 ;9:e43114.
        BACKGROUND: Globally, men who have sex with men (MSM) continue to bear a disproportionately high burden of HIV infection. Rwanda experiences a mixed HIV epidemic, which is generalized in the adult population, with aspects of a concentrated epidemic among certain key populations at higher risk of HIV infection, including MSM. Limited data exist to estimate the population size of MSM at a national scale; hence, an important piece is missing in determining the denominators to use in estimates for policy makers, program managers, and planners to effectively monitor HIV epidemic control. OBJECTIVE: The aims of this study were to provide the first national population size estimate (PSE) and geographic distribution of MSM in Rwanda. METHODS: Between October and December 2021, a three-source capture-recapture method was used to estimate the MSM population size in Rwanda. Unique objects were distributed to MSM through their networks (first capture), who were then tagged according to MSM-friendly service provision (second capture), and a respondent-driven sampling survey was used as the third capture. Capture histories were aggregated in a 2k-1 contingency table, where k indicates the number of capture occasions and "1" and "0" indicate captured and not captured, respectively. Statistical analysis was performed in R (version 4.0.5) and the Bayesian nonparametric latent-class capture-recapture package was used to produce the final PSE with 95% credibility sets (CS). RESULTS: We sampled 2465, 1314, and 2211 MSM in capture one, two, and three, respectively. There were 721 recaptures between captures one and two, 415 recaptures between captures two and three, and 422 recaptures between captures one and three. There were 210 MSM captured in all three captures. The total estimated population size of MSM above 18 years old in Rwanda was 18,100 (95% CS 11,300-29,700), corresponding to 0.70% (95% CI 0.4%-1.1%) of total adult males. Most MSM reside in the city of Kigali (7842, 95% CS 4587-13,153), followed by the Western province (2469, 95% CS 1994-3518), Northern province (2375, 95% CS 842-4239), Eastern province (2287, 95% CS 1927-3014), and Southern province (2109, 95% CS 1681-3418). CONCLUSIONS: Our study provides, for the first time, a PSE of MSM aged 18 years or older in Rwanda. MSM are concentrated in the city of Kigali and are almost evenly distributed across the other 4 provinces. The national proportion estimate bounds of MSM out of the total adult males includes the World Health Organization's minimum recommended proportion (at least 1.0%) based on 2012 census population projections for 2021. These results will inform denominators to be used for estimating service coverage and fill existing information gaps to enable policy makers and planners to monitor the HIV epidemic among MSM nationally. There is an opportunity for conducting small-area MSM PSEs for subnational-level HIV treatment and prevention interventions.

        Musengimana, G. Malamba, S. Moges, H. Kankindi, I. Habimana Kabano, I. Oluoch, T.

      3. Sources of variation in estimates of Duchenne and Becker muscular dystrophy prevalence in the United States
        Whitehead N, Erickson SW, Cai B, McDermott S, Peay H, Howard JF, Ouyang L.
        Orphanet J Rare Dis. 2023 ;18(1):65.
        BACKGROUND: Direct estimates of rare disease prevalence from public health surveillance may only be available in a few catchment areas. Understanding variation among observed prevalence can inform estimates of prevalence in other locations. The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducts population-based surveillance of major muscular dystrophies in selected areas of the United States. We identified sources of variation in prevalence estimates of Duchenne and Becker muscular dystrophy (DBMD) within MD STARnet from published literature and a survey of MD STARnet investigators, then developed a logic model of the relationships between the sources of variation and estimated prevalence. RESULTS: The 17 identified sources of variability fell into four categories: (1) inherent in surveillance systems, (2) particular to rare diseases, (3) particular to medical-records-based surveillance, and (4) resulting from extrapolation. For the sources of uncertainty measured by MD STARnet, we estimated each source's contribution to the total variance in DBMD prevalence. Based on the logic model we fit a multivariable Poisson regression model to 96 age-site-race/ethnicity strata. Age accounted for 74% of the variation between strata, surveillance site for 6%, race/ethnicity for 3%, and 17% remained unexplained. CONCLUSION: Variation in estimates derived from a non-random sample of states or counties may not be explained by demographic differences alone. Applying these estimates to other populations requires caution.

        Ouyang, L.

      4. Household surveillance for norovirus gastroenteritis in a Nicaraguan birth cohort: A nested case-control analysis of norovirus risk factors
        Vielot NA, Zepeda O, Reyes Y, González F, Vinjé J, Becker-Dreps S, Bucardo F.
        Pathogens. 2023 ;12(3).
        Norovirus causes a large proportion of pediatric acute gastroenteritis (AGE) worldwide, and no vaccines are currently available. To inform public health measures against norovirus gastroenteritis, we assessed risk factors in a case-control study nested in a birth cohort study in Nicaragua. Between June 2017 and January 2022, we followed children weekly for AGE episodes, and collected stool specimens from symptomatic children. Risk factors for AGE were collected during routine weekly visits. Norovirus was detected in stools using real-time reverse transcriptase polymerase chain reaction and positive specimens were genotyped using Sanger sequencing. We included 40 norovirus-positive AGE children matched 1:2 to controls and conducted bivariate and multivariable analyses of norovirus AGE risk factors. Among typeable norovirus infections, GII.4 were more severe than non-GII.4 (four/twenty-one vs. one/nine) and accounted for all emergency visits and hospitalizations. Adjusted conditional logistic regression found that female sex and higher length-for-age Z score were protective against norovirus AGE; a dirt floor in the home, sharing cups or bottles, and recent contact with someone with AGE symptoms were associated with norovirus AGE, though estimates were highly imprecise. Reducing contact with symptomatic persons and with saliva or other bodily fluids on cups or floors could reduce infant norovirus incidence.

        Vinjé, J.

      5. Etiologies of influenza-like illness and severe acute respiratory infections in Tanzania, 2017-2019
        Kelly ME, Gharpure R, Shivji S, Matonya M, Moshi S, Mwafulango A, Mwalongo V, Mghamba J, Simba A, Balajee SA, Gatei W, Mponela M, Saguti G, Whistler T, Moremi N, Mmbaga V.
        PLOS Glob Public Health. 2023 ;3(2):e0000906.
        In 2016, Tanzania expanded sentinel surveillance for influenza-like illness (ILI) and severe acute respiratory infection (SARI) to include testing for non-influenza respiratory viruses (NIRVs) and additional respiratory pathogens at 9 sentinel sites. During 2017-2019, respiratory specimens from 2730 cases underwent expanded testing: 2475 specimens (90.7%) were tested using a U.S. Centers for Disease Control and Prevention (CDC)-developed assay covering 7 NIRVs (respiratory syncytial virus [RSV], rhinovirus, adenovirus, human metapneumovirus, parainfluenza virus 1, 2, and 3) and influenza A and B viruses. Additionally, 255 specimens (9.3%) were tested using the Fast-Track Diagnostics Respiratory Pathogens 33 (FTD-33) kit which covered the mentioned viruses and additional viral, bacterial, and fungal pathogens. Influenza viruses were identified in 7.5% of all specimens; however, use of the CDC assay and FTD-33 kit increased the number of specimens with a pathogen identified to 61.8% and 91.5%, respectively. Among the 9 common viruses between the CDC assay and FTD-33 kit, the most identified pathogens were RSV (22.9%), rhinovirus (21.8%), and adenovirus (14.0%); multi-pathogen co-detections were common. Odds of hospitalization (SARI vs. ILI) varied by sex, age, geographic zone, year of diagnosis, and pathogen identified; hospitalized illnesses were most common among children under the age of 5 years. The greatest number of specimens were submitted for testing during December-April, coinciding with rainy seasons in Tanzania, and several viral pathogens demonstrated seasonal variation (RSV, human metapneumovirus, influenza A and B, and parainfluenza viruses). This study demonstrates that expanding an existing influenza platform to include additional respiratory pathogens can provide valuable insight into the etiology, incidence, severity, and geographic/temporal patterns of respiratory illness. Continued respiratory surveillance in Tanzania, and globally, can provide valuable data, particularly in the context of emerging respiratory pathogens such as SARS-CoV-2, and guide public health interventions to reduce the burden of respiratory illnesses.

        Gharpure, R. Shivji, S. Balajee, S. A. Gatei, W. Whistler, T.

      6. Tracking COVID-19 in the United States with surveillance of aggregate cases and deaths
        Khan D, Park M, Burkholder J, Dumbuya S, Ritchey MD, Yoon P, Galante A, Duva JL, Freeman J, Duck W, Soroka S, Bottichio L, Wellman M, Lerma S, Lyons BC, Dee D, Haile S, Gaughan DM, Langer A, Gundlapalli AV, Suthar AB.
        Public Health Rep. 2023 :333549231163531.
        Early during the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) leveraged an existing surveillance system infrastructure to monitor COVID-19 cases and deaths in the United States. Given the time needed to report individual-level (also called line-level) COVID-19 case and death data containing detailed information from individual case reports, CDC designed and implemented a new aggregate case surveillance system to inform emergency response decisions more efficiently, with timelier indicators of emerging areas of concern. We describe the processes implemented by CDC to operationalize this novel, multifaceted aggregate surveillance system for collecting COVID-19 case and death data to track the spread and impact of the SARS-CoV-2 virus at national, state, and county levels. We also review the processes established to acquire, process, and validate the aggregate number of cases and deaths due to COVID-19 in the United States at the county and jurisdiction levels during the pandemic. These processes include time-saving tools and strategies implemented to collect and validate authoritative COVID-19 case and death data from jurisdictions, such as web scraping to automate data collection and algorithms to identify and correct data anomalies. This topical review highlights the need to prepare for future emergencies, such as novel disease outbreaks, by having an event-agnostic aggregate surveillance system infrastructure in place to supplement line-level case reporting for near-real-time situational awareness and timely data.

        Khan, D. Park, M. Burkholder, J. Dumbuya, S. Ritchey, M. D. Yoon, P. Duck, W. Soroka, S. Bottichio, L. Wellman, M. Lerma, S. Lyons, B. C. Dee, D. Haile, S. Gaughan, D. M. Langer, A. Gundlapalli, A. V. Suthar, A. B.

    • Genetics and Genomics
      1. Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
        Eriksen HB, Fuursted K, Jensen A, Jensen CS, Nielsen X, Christensen JJ, Shewmaker P, Rebelo AR, Aarestrup FM, Schønning K, Slotved HC.
        Front Microbiol. 2023 ;14:1120023.
        INTRODUCTION: For Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS. METHOD: Isolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression. RESULTS: Among 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone). CONCLUSION: Using a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.

        Shewmaker, P.

      2. Discovery and characterization of pneumococcal serogroup 36 capsule subtypes, serotypes 36A and 36B
        Ganaie FA, Saad JS, Lo SW, McGee L, Bentley SD, van Tonder AJ, Hawkins P, Keenan JD, Calix JJ, Nahm MH.
        J Clin Microbiol. 2023 :e0002423.
        Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized. Prior sequence analysis of pneumococcal capsule synthesis (cps) loci suggested the existence of capsule subtypes among isolates identified as "serotype 36" according to conventional capsule typing methods. We discovered these subtypes represent two antigenically similar but distinguishable pneumococcal capsule serotypes, 36A and 36B. Biochemical analysis of their capsule PS structure reveals that both have the shared repeat unit backbone [→5)-α-d-Galf-(1→1)-d-Rib-ol-(5→P→6)-β-d-ManpNAc-(1→4)-β-d-Glcp-(1→] with two branching structures. Both serotypes have a β-d-Galp branch to Ribitol. Serotypes 36A and 36B differ by the presence of a α-d-Glcp-(1→3)-β-d-ManpNAc or α-d-Galp-(1→3)-β-d-ManpNAc branch, respectively. Comparison of the phylogenetically distant serogroup 9 and 36 cps loci, which all encode this distinguishing glycosidic bond, revealed that the incorporation of Glcp (in types 9N and 36A) versus Galp (in types 9A, 9V, 9L, and 36B) is associated with the identity of four amino acids in the cps-encoded glycosyltransferase WcjA. Identifying functional determinants of cps-encoded enzymes and their impact on capsule PS structure is key to improving the resolution and reliability of sequencing-based capsule typing methods and discovering novel capsule variants indistinguishable by conventional serotyping methods.

        McGee, L.

    • Global Health
      1. Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021
        Dunajcik A, Haire K, Thomas JD, Moriarty LF, Springer Y, Villanueva JM, MacNeil A, Silk B, Nemhauser JB, Byrkit R, Taylor M, Queen K, Tong S, Lee J, Batra D, Paden C, Henderson T, Kunkes A, Ojo M, Firestone M, Martin Webb L, Freeland M, Brown CM, Williams T, Allen K, Kauerauf J, Wilson E, Jain S, McDonald E, Silver E, Stous S, Wadford D, Radcliffe R, Marriott C, Owes JP, Bart SM, Sosa LE, Oakeson K, Wodniak N, Shaffner J, Brown Q, Westergaard R, Salinas A, Hallyburton S, Ogale Y, Offutt-Powell T, Bonner K, Tubach S, Van Houten C, Hughes V, Reeb V, Galeazzi C, Khuntia S, McGee S, Hicks JT, Dinesh Patel D, Krueger A, Hughes S, Jeanty F, Wang JC, Lee EH, Assanah-Deane T, Tompkins M, Dougherty K, Naqvi O, Donahue M, Frederick J, Abdalhamid B, Powers AM, Anderson M.
        PLOS Glob Public Health. 2023 ;3(3):e0001252.
        The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs.

        Dunajcik, A. Haire, K. Thomas, J. D. Moriarty, L. F. Springer, Y. Villanueva, J. M. MacNeil, A. Silk, B. Nemhauser, J. B. Byrkit, R. Taylor, M. Queen, K. Tong, S. Lee, J. Batra, D. Paden, C. Shaffner, J. Powers, A. M. Anderson, M.

    • Health Economics
      1. Delivery cost of the first public sector introduction of typhoid conjugate vaccine in Navi Mumbai, India
        Song D, Pallas SW, Shimpi R, Ramaswamy N, Haldar P, Harvey P, Bhatnagar P, Katkar A, Jayaprasad N, Kunwar A, Bahl S, Morgan W, Hutubessy R, Date K, Mogasale V.
        PLOS Glob Public Health. 2023 ;3(1):e0001396.
        Navi Mumbai Municipal Corporation (NMMC), a local government in Mumbai, India, implemented the first public sector TCV campaign in 2018. This study estimated the delivery costs of this TCV campaign using a Microsoft Excel-based tool based on a micro-costing approach from the government (NMMC) perspective. The campaign's financial (direct expenditures) and economic costs (financial costs plus the monetized value of additional donated or existing items) incremental to the existing immunization program were collected. The data collection methods involved consultations with NMMC staff, reviews of financial and programmatic records of NMMC and the World Health Organization (WHO), and interviews with the health staff of sampled urban health posts (UHPs). Three UHPs were purposively sampled, representing the three dominant residence types in the catchment area: high-rise, slum, and mixed (high-rise and slum) areas. The high-rise area UHP had lower vaccination coverage (47%) compared with the mixed area (71%) and slum area UHPs (76%). The financial cost of vaccine and vaccination supplies (syringes, safety boxes) was $1.87 per dose, and the economic cost was $2.96 per dose in 2018 US dollars. Excluding the vaccine and vaccination supplies cost, the financial delivery cost across the 3 UHPs ranged from $0.37 to $0.53 per dose, and the economic delivery cost ranged from $1.37 to $3.98 per dose, with the highest delivery costs per dose in the high-rise areas. Across all 11 UHPs included in the campaign, the weighted average financial delivery cost was $0.38 per dose, and the economic delivery cost was $1.49 per dose. WHO has recommended the programmatic use of TCV in typhoid-endemic countries, and Gavi has included TCV in its vaccine portfolio. This first costing study of large-scale TCV introduction within a public sector immunization program provides empirical evidence for policymakers, stakeholders, and future vaccine campaign planning.

        Pallas, S. W.

      2. The epidemiology and costs of disease intervention specialist retention
        Becher J, Salmon ME, Gift TL.
        Sex Transm Dis. 2023 .
        INTRODUCTION: The COVID-19 pandemic changed the environment in which disease intervention specialists (DIS) operate, as their skills were in demand beyond STD control programs. Workforce conditions generally have changed in the last 2 years, imposing additional challenges. Retaining STD DIS has become more difficult in the changed environment. MATERIALS AND METHODS: We conducted a landscape scan and obtained data from literature and personal observations to characterize current DIS workforce issues. We used published employment data to characterize current labor market conditions and described how cost-effectiveness analysis could be used to assess potential DIS retention interventions. An example illustrating cost-effectiveness concepts was developed. RESULTS: Many STD control programs faced difficulties in retaining STD DIS, because competing positions often could be done without field work. Economic and crime issues posed additional challenges. General workforce turnover has increased 33% since 2016. Turnover varies by age, gender, and education. Cost-effectiveness analysis can be used to assess DIS retention interventions, but data on costs and outcomes are needed on an ongoing basis. Changes in the workforce environment could impact both retention and the effectiveness of retention interventions. CONCLUSIONS: Workforce changes have impacted employee retention. Increased federal funding makes expansion of the DIS workforce possible, but the labor market environment will continue to pose challenges to recruitment and retention.

        Becher, J. Salmon, M. E. Gift, T. L.

    • Health Equity and Health Disparities
      1. Neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis
        Neo DT, Desrosiers TA, Martin CL, Carmichael SL, Gucsavas-Calikoglu M, Conway KM, Evans SP, Feldkamp ML, Gilboa SM, Insaf TZ, Musfee FI, Shaw GM, Shumate CJ, Werler MM, Olshan AF.
        Epidemiology. 2023 .
        BACKGROUND: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the understudied association between neighborhood-level socioeconomic position during early pregnancy and risk of gastroschisis, an abdominal birth defect of increasing prevalence. METHODS: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997 - 2011). To characterize neighborhood-level socioeconomic position, we conducted principal component analysis to construct two indices - Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputation for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence. RESULTS: Mothers residing in moderate (NDI Tertile 2 aOR: 1.2; 95% CI: 1.0, 1.5 and nSEPI Tertile 2 aOR: 1.2; 95% CI: 1.0, 1.5) or low socioeconomic neighborhoods (NDI Tertile 3 aOR: 1.3; 95% CI: 1.01, 1.6 and nSEPI Tertile 3 aOR: 1.3, 95% CI: 1.1, 1.6) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods. CONCLUSIONS: Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis.

        Gilboa, S. M.

      2. Food insecurity and adequacy of dietary intake in youth and young adults with youth-onset type 1 and type 2 diabetes
        Bercaw H, Reid LA, Mendoza JA, Frongillo EA, Sauder KA, Reboussin BA, Mayer-Davis EJ, Dabelea D, Marcovina SM, Mercado C, Liese AD.
        J Acad Nutr Diet. 2023 .
        BACKGROUND: Household food insecurity is associated with poor dietary intake in the general population, but little is known about this association in persons with diabetes. OBJECTIVE: We examined the degree of adherence to the dietary reference intakes and 2020-2025 Dietary Guidelines for Americans overall and according to food security status and diabetes type among youth and young adults (YYA) with youth-onset diabetes. DESIGN: /Participants/Setting: The SEARCH for Diabetes in Youth study includes 1,197 YYA with type 1 diabetes (T1D, mean age: 21 years ± 5) and 319 YYA with type 2 diabetes (T2D, 25 years ± 4). Participants (or parents if <18 years) completed the USDA Household Food Security Survey Module, wherein ≥3 affirmations indicate food insecurity. MAIN OUTCOME MEASURES: Diet was assessed via food frequency questionnaire and compared to age- and sex-specific dietary reference intakes for 10 nutrients and dietary components (calcium, fiber, magnesium, potassium, sodium, vitamins C, D, E, added sugar, saturated fat). STATISTICAL ANALYSES PERFORMED: Median regression models controlled for sex- and type-specific means for age, diabetes duration, and daily energy intake. RESULTS: Prevalence of guideline adherence was overarchingly poor, with <40% of participants meeting recommendations for 8 of 10 nutrients and dietary components; however, higher adherence (>47%) was observed for vitamin C and added sugars. YYA with T1D who were food insecure were more likely to meet recommendations for calcium, magnesium, and vitamin E (p<0.05), and less likely for sodium (p<0.05) than those food secure. In adjusted models, YYA with T1D who were food secure had closer median adherence to sodium (p=0.002) and fiber (p=0.042) guidelines than those food insecure. No associations were observed in YYA with T2D. CONCLUSIONS: Food insecurity is associated with lesser adherence to fiber and sodium guidelines in YYA with T1D, which may lead to diabetes complications, and other chronic diseases.

        Mercado, C.


    • Immunity and Immunization
      1. Influenza vaccine effectiveness among children: 2011-2020
        Hood N, Flannery B, Gaglani M, Beeram M, Wernli K, Jackson ML, Martin ET, Monto AS, Zimmerman R, Raviotta J, Belongia EA, McLean HQ, Kim S, Patel MM, Chung JR.
        Pediatrics. 2023 .
        BACKGROUND AND OBJECTIVES: Infants and children are at increased risk of severe influenza virus infection and its complications. Influenza vaccine effectiveness (VE) varies by age, influenza season, and influenza virus type/subtype. This study's objective was to examine the effectiveness of inactivated influenza vaccine against outpatient influenza illness in the pediatric population over 9 influenza seasons after the 2009 A(H1N1) pandemic. METHODS: During the 2011-2012 through the 2019-2020 influenza seasons at outpatient clinics at 5 sites of the US Influenza Vaccine Effectiveness Network, children aged 6 months to 17 years with an acute respiratory illness were tested for influenza using real-time, reverse-transcriptase polymerase chain reaction. Vaccine effectiveness was estimated using a test-negative design. RESULTS: Among 24 148 enrolled children, 28% overall tested positive for influenza, 3017 tested positive for influenza A(H3N2), 1459 for influenza A(H1N1)pdm09, and 2178 for influenza B. Among all enrollees, 39% overall were vaccinated, with 29% of influenza cases and 43% of influenza-negative controls vaccinated. Across all influenza seasons, the pooled VE for any influenza was 46% (95% confidence interval, 43-50). Overall and by type/subtype, VE against influenza illness was highest among children in the 6- to 59-month age group compared with older pediatric age groups. VE was lowest for influenza A(H3N2) virus infection. CONCLUSIONS: Analysis of multiple seasons suggested substantial benefit against outpatient illness. Investigation of host-specific or virus-related mechanisms that may result in differences by age and virus type/subtype may help further efforts to promote increased vaccination coverage and other influenza-related preventative measures.

        Hood, N. Flannery, B. Kim, S. Patel, M. M. Chung, J. R.

      2. Health care provider knowledge around shared clinical decision-making regarding HPV vaccination of adults aged 27-45 years in the United States
        Gidengil CA, Parker AM, Markowitz LE, Gedlinske AM, Askelson NM, Petersen CA, Meites E, Lindley MC, Scherer AM.
        Vaccine. 2023 .
        BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends shared clinical decision-making (SCDM) regarding HPV vaccination for adults aged 27-45 years who are not adequately vaccinated. The objective of this survey was to understand physician knowledge, attitudes, and practices regarding HPV vaccination in this age group. METHODS: An online survey was administered in June 2021 to physicians who reported practicing internal medicine, family medicine, or obstetrics and gynecology (targeted N = 250 in each practice specialty), selected randomly from potentially eligible physicians from a panel of 2 million U.S. health care providers. RESULTS: In total, 753 physicians participated in the survey: 33.3% practiced internal medicine, 33.1% practiced family medicine, and 33.6% practiced obstetrics/gynecology; 62.5% were male and mean physician age was 52.7 years. Despite the COVID-19 pandemic, at least a third of participating physicians in each practice specialty reported having more HPV vaccine SCDM discussions with patients aged 27-45 years in the past 12 months. While a majority of physicians (79.7%) reported being aware of the SCDM recommendation for adults in this age group, only half of physicians answered an objective knowledge question about SCDM recommendations correctly. CONCLUSIONS: Findings suggest that there are physician knowledge gaps related to SCDM for HPV vaccination. To improve access to HPV vaccination for people most likely to benefit, increasing availability and use of decision aids to support SCDM discussions might help healthcare providers and patients jointly make the most informed decisions about HPV vaccination.

        Markowitz, L. E. Meites, E. Lindley, M. C.

      3. Serologic responses to COVID-19 vaccination in children with history of multisystem inflammatory syndrome (MIS-C)
        Perez MA, Hsiao HM, Chen X, Kunkel A, Baida N, Hussaini L, Lu AT, Kao CM, Laham FR, Hunstad DA, Beltran Y, Hammett TA, Godfred-Cato S, Chahroudi A, Anderson EJ, Belay E, Rostad CA.
        Vaccine. 2023 .
        Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled seven children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies variably waned following acute MIS-C, but were significantly boosted with vaccination and maintained for up to 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n = 16) and children with history of MIS-C (n = 7) or COVID-19 (n = 8). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were significantly reduced to the Omicron variant.

        Kunkel, A. Hammett, T. A. Godfred-Cato, S.

    • Informatics
      1. Operational characteristics of central cancer registries that support the generation of high-quality surveillance data
        Edwards P, Bernacet A, Tangka FK, Pordell P, Beizer J, Wilson R, Blumenthal W, Jones SF, Cole-Beebe M, Subramanian S.
        J Registry Manag. 2022 ;49(1):10-16.
        OBJECTIVES: We aim to assess external and internal attributes and operations of the Centers for Disease Control and Prevention (CDC)'s National Program of Cancer Registries (NPCR) central cancer registries by their consistency in meeting national data quality standards. METHODS: The NPCR 2017 Program Evaluation Instrument (PEI) data were used to assess registry operational attributes, including adoption of electronic reporting, compliance with reporting, staffing, and software used among 46 NPCR registries. These factors were stratified by (1) registries that met the NPCR 12-month standards for all years 2014-2017; (2) registries that met the NPCR 12-month standards at least once in 2014-2017 and met the NPCR 24-month standards for all years 2014-2017; and (3) registries that did not meet the NPCR 24-month standards for all years 2014-2017. Statistical tests helped identify significant differences among registries that consistently, sometimes, or seldom/never achieved data standards. RESULTS: Registries that always met the standards had a higher level of electronic reporting and a higher compliance with reporting among hospitals than registries that sometimes or seldom/never met the standards. Although not a statistically significant finding, the same registries also had a higher proportion of staffing positions filled, a higher proportion of certified tumor registrars, and more quality assurance and information technology staff. CONCLUSIONS: This information may be used to understand the importance of various factors and characteristics, including the adoption of electronic reporting, that may be associated with a registry's ability to consistently meet NPCR standards. The findings may be helpful in identifying best practices for processing high-quality cancer data.

        Tangka, F. K. L. Pordell, P. Wilson, R. Blumenthal, W. Jones, S. F.

      2. Fungal diseases are frequently coded as "unspecified mycoses" in data sets used to estimate disease burden. In a large administrative database, 50.9% of unspecified mycosis hospitalizations during 2019-2021 had positive fungal laboratory testing, most commonly Candida (79.1%), highlighting a potential need for improved coding practices and greater fungal laboratory testing.

        Benedict, K. Baggs, J. Wolford, H. Jackson, B. R. Gold, J. A. W.

    • Injury and Violence
      1. Purpose: The pathways by which adverse childhood experiences (ACEs) are associated with early marriage and early pregnancy are poorly understood. Early marriage and early pregnancy may be risk factors for adulthood intimate partner violence (IPV). The aim of this study was to assess the relationships among ACEs, early marriage, early pregnancy, and IPV among women in Honduras. Method: We used weighted data from 1,436 women aged 18–24 years from the nationally representative 2017 Honduras Violence Against Children and Youth Survey. We used path analysis to estimate relationships and accounted for sample design, non-response, and within-country clustering. Results: We found that ACEs had differential relationships with outcomes of interest. For example, witnessing violence in the community was directly associated with increased probability of early pregnancy (10 percentage points (PP); 95% CI: 0.04, 0.15) and IPV (6 PP; 95% CI: 0.01, 0.10), while emotional violence was not directly or indirectly associated with any outcome. Early marriage and early pregnancy had no direct or indirect effect on IPV, but the total effect of early marriage on IPV was significant. Conclusions: Understanding the relationship between ACEs, early marriage, early pregnancy, and IPV may help inform prevention efforts. For example, programs aiming to reduce early pregnancy may consider addressing sexual violence experienced in childhood. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

        Huber-Krum, S. Miedema, S. S. Shortt, J. W. Villaveces, A. Kress, H.

      2. OBJECTIVE: To develop syndromic surveillance definitions for unintentional fall- and hip fracture-related emergency department (ED) visits among older adults (aged ≥65 years) for use in the Centers for Disease Control and Prevention's National Syndromic Surveillance Program (NSSP) data and compare the percentage of ED visits captured using these new syndromes with ED visits from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample (HCUP-NEDS), a nationally representative administrative data set. DESIGN/SETTING: Syndromic definitions were developed using chief complaint terms and discharge diagnosis codes in NSSP data. The percentages of ED visits among older adults related to falls and hip fractures in NSSP were compared with the percentages in HCUP-NEDS in 2017 and 2018. MEASURES: Prevalence ratios were calculated as the relative difference in the percentage of ED visits related to falls or hip fractures in NSSP compared with HCUP-NEDS. Counts and percentages calculated using HCUP-NEDS were weighted to produce nationally representative estimates. Data were analyzed overall and by sex and age group. RESULTS: The percentage of ED visits among older adults related to falls in NSSP was 12% less in 2017 (10.81%) and 7% less in 2018 (11.42%) compared with HCUP-NEDS (2017: 12.30%; 2018: 12.26%). The percentage of ED visits among older adults related to hip fractures in NSSP was 41% less in 2017 (0.65%) and 30% less in 2018 (0.76%) compared with HCUP-NEDS (2017: 1.10%; 2018: 1.09%). In both 2017 and 2018, a higher percentage of ED visits among older women and adults aged 85 years or older were related to falls or hip fractures compared with older men and younger age groups across both data sets. CONCLUSION: A smaller percentage of older adults' ED visits met the falls and hip fracture definitions in NSSP compared with HCUP-NEDS in 2017 and 2018. However, demographic trends remained similar across both data sets.

        Moreland, B. Shakya, I. Idaikkadar, N.

      3. Evaluation of the Nigeria national HIV rapid testing algorithm
        Iriemenam NC, Mpamugo A, Ikpeazu A, Okunoye OO, Onokevbagbe E, Bassey OO, Tapdiyel J, Alagi MA, Meribe C, Ahmed ML, Ikwulono G, Aguolu R, Ashefor G, Nzelu C, Ehoche A, Ezra B, Obioha C, Baffa Sule I, Adedokun O, Mba N, Ihekweazu C, Charurat M, Lindsay B, Stafford KA, Ibrahim D, Swaminathan M, Yufenyuy EL, Parekh BS, Adebajo S, Abimiku A, Okoye MI.
        PLOS Glob Public Health. 2022 ;2(11):e0001077.
        Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary.

        Iriemenam, N. C. Okunoye, O. O. Bassey, O. O. Tapdiyel, J. Alagi, M. A. Meribe, C. Ahmed, M. L. Ibrahim, D. Swaminathan, M. Yufenyuy, E. L. Okoye, M. I.

    • Laboratory Sciences
      1. Design and optimization of a monkeypox virus specific serological assay
        Taha TY, Townsend MB, Pohl J, Karem KL, Damon IK, Mbala Kingebeni P, Muyembe Tamfum JJ, Martin JW, Pittman PR, Huggins JW, Satheshkumar PS, Bagarozzi DA, Reynolds MG, Hughes LJ.
        Pathogens. 2023 ;12(3).
        Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak.

        Taha, T. Y. Townsend, M. B. Pohl, J. Karem, K. L. Damon, I. K. Satheshkumar, P. S. Bagarozzi, D. A., Jr. Reynolds, M. G. Hughes, L. J.

      2. Implementing mailed colorectal cancer fecal screening tests in real-world primary care settings: Promising implementation practices and opportunities for improvement
        Hohl SD, Maxwell AE, Sharma KP, Sun J, Vu TT, DeGroff A, Escoffery C, Schlueter D, Hannon PA.
        Prev Sci. 2023 :1-12.
        Colorectal cancer (CRC) screening reduces morbidity and mortality, but screening rates in the USA remain suboptimal. The Colorectal Cancer Control Program (CRCCP) was established in 2009 to increase screening among groups disproportionately affected. The CRCCP utilizes implementation science to support health system change as a strategy to reduce disparities in CRC screening by directing resources to primary care clinics to implement evidence-based interventions (EBIs) proven to increase CRC screening. As COVID-19 continues to impede in-person healthcare visits and compel the unpredictable redirection of clinic priorities, understanding clinics' adoption and implementation of EBIs into routine care is crucial. Mailed fecal testing is an evidence-based screening approach that offers an alternative to in-person screening tests and represents a promising approach to reduce CRC screening disparities. However, little is known about how mailed fecal testing is implemented in real-world settings. In this retrospective, cross-sectional analysis, we assessed practices around mailed fecal testing implementation in 185 clinics across 62 US health systems. We sought to (1) determine whether clinics that do and do not implement mailed fecal testing differ with respect to characteristics (e.g., type, location, and proportion of uninsured patients) and (2) identify implementation practices among clinics that offer mailed fecal testing. Our findings revealed that over half (58%) of clinics implemented mailed fecal testing. These clinics were more likely to have a CRC screening policy than clinics that did not implement mailed fecal testing (p = 0.007) and to serve a larger patient population (p = 0.004), but less likely to have a large proportion of uninsured patients (p = 0.01). Clinics that implemented mailed fecal testing offered it in combination with EBIs, including patient reminders (92%), provider reminders (94%), and other activities to reduce structural barriers (95%). However, fewer clinics reported having the leadership support (58%) or funding stability (29%) to sustain mailed fecal testing. Mailed fecal testing was widely implemented alongside other EBIs in primary care clinics participating in the CRCCP, but multiple opportunities for enhancing its implementation exist. These include increasing the proportion of community health centers/federally qualified health centers offering mailed screening; increasing the proportion that provide pre-paid return mail supplies with the screening kit; increasing the proportion of clinics monitoring both screening kit distribution and return; ensuring patients with abnormal tests can obtain colonoscopy; and increasing sustainability planning and support.

        DeGroff, A. Schlueter, D.

    • Maternal and Child Health
      1. Multi-laboratory evaluation of prototype dried blood spot quality control materials for creatine kinase-MM newborn screening assays
        Dantonio P, Tavakoli NP, Migliore B, McCown E, Lim T, Park S, Caggana M, Kucera KS, Phan H, Street N, Petritis K, Vogt RF.
        Int J Neonatal Screen. 2023 ;9(1).
        Pilot studies to detect newborns with Duchenne Muscular Dystrophy (DMD) by newborn bloodspot screening (NBS) have been conducted under the New York State Newborn Screening Program (NYS) and are currently in progress as part of the Early Check Program at Research Triangle Institute (RTI) International. The Newborn Screening Quality Assurance Program (NSQAP) at the U.S. Centers for Disease Control and Prevention (CDC) produced a set of seven prototype dried blood spot (DBS) reference materials spiked with varying levels of creatine kinase MM isoform (CK-MM). These DBS were evaluated over a 3-week period by CDC, NYS, and RTI, all using the same CK-MM isoform-specific fluoroimmunoassay. Results from each laboratory were highly correlated with the relative proportion of CK-MM added to each of the six spiked pools. Based on reference ranges established by NYS and RTI for their pilot studies, these contrived DBS collectively spanned the CK-MM ranges found in typical newborns and the elevated ranges associated with DMD. This set allows quality assessment over the wide range of fluctuating CK-MM levels in typical and DMD-affected newborns.

        Dantonio, P. Tavakoli, N. P. Migliore, B. McCown, E. Lim, T. Street, N. Petritis, K. Vogt, R. F.

      2. Harmonization of newborn screening results for Pompe disease and Mucopolysaccharidosis Type I
        Dorley MC, Dizikes GJ, Pickens CA, Cuthbert C, Basheeruddin K, Gulamali-Majid F, Hetterich P, Hietala A, Kelsey A, Klug T, Lesko B, Mills M, Moloney S, Neogi P, Orsini J, Singer D, Petritis K.
        Int J Neonatal Screen. 2023 ;9(1).
        In newborn screening, false-negative results can be disastrous, leading to disability and death, while false-positive results contribute to parental anxiety and unnecessary follow-ups. Cutoffs are set conservatively to prevent missed cases for Pompe and MPS I, resulting in increased falsepositive results and lower positive predictive values. Harmonization has been proposed as a way to minimize false-negative and false-positive results and correct for method differences, so we harmonized enzyme activities for Pompe and MPS I across laboratories and testing methods (Tandem Mass Spectrometry (MS/MS) or Digital Microfluidics (DMF)). Participating states analyzed proofof- concept calibrators, blanks, and contrived specimens and reported enzyme activities, cutoffs, and other testing parameters to Tennessee. Regression and multiples of the median were used to harmonize the data. We observed varied cutoffs and results. Six of seven MS/MS labs reported enzyme activities for one specimen for MPS I marginally above their respective cutoffs with results classified as negative, whereas all DMF labs reported this specimen's enzyme activity below their respective cutoffs with results classified as positive. Reasonable agreement in enzyme activities and cutoffs was achieved with harmonization; however, harmonization does not change how a value would be reported as this is dependent on the placement of cutoffs.

        Pickens, C. A. Cuthbert, C. Petritis, K.


      4. Prevalence and characteristics of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2020
        Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Ladd-Acosta CM, McArthur D, Pas ET, Salinas A, Vehorn A, Williams S, Esler A, Grzybowski A, Hall-Lande J, Nguyen RH, Pierce K, Zahorodny W, Hudson A, Hallas L, Mancilla KC, Patrick M, Shenouda J, Sidwell K, DiRienzo M, Gutierrez J, Spivey MH, Lopez M, Pettygrove S, Schwenk YD, Washington A, Shaw KA.
        MMWR Surveill Summ. 2023 ;72(2):1-14.
        PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2020. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years. In 2020, there were 11 ADDM Network sites across the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. A child met the case definition if their record documented 1) an ASD diagnostic statement in an evaluation, 2) a classification of ASD in special education, or 3) an ASD International Classification of Diseases (ICD) code. RESULTS: For 2020, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 23.1 in Maryland to 44.9 in California. The overall ASD prevalence was 27.6 per 1,000 (one in 36) children aged 8 years and was 3.8 times as prevalent among boys as among girls (43.0 versus 11.4). Overall, ASD prevalence was lower among non-Hispanic White children (24.3) and children of two or more races (22.9) than among non-Hispanic Black or African American (Black), Hispanic, and non-Hispanic Asian or Pacific Islander (A/PI) children (29.3, 31.6, and 33.4 respectively). ASD prevalence among non-Hispanic American Indian or Alaska Native (AI/AN) children (26.5) was similar to that of other racial and ethnic groups. ASD prevalence was associated with lower household income at three sites, with no association at the other sites.Across sites, the ASD prevalence per 1,000 children aged 8 years based exclusively on documented ASD diagnostic statements was 20.6 (range = 17.1 in Wisconsin to 35.4 in California). Of the 6,245 children who met the ASD case definition, 74.7% had a documented diagnostic statement of ASD, 65.2% had a documented ASD special education classification, 71.6% had a documented ASD ICD code, and 37.4% had all three types of ASD indicators. The median age of earliest known ASD diagnosis was 49 months and ranged from 36 months in California to 59 months in Minnesota.Among the 4,165 (66.7%) children with ASD with information on cognitive ability, 37.9% were classified as having an intellectual disability. Intellectual disability was present among 50.8% of Black, 41.5% of A/PI, 37.8% of two or more races, 34.9% of Hispanic, 34.8% of AI/AN, and 31.8% of White children with ASD. Overall, children with intellectual disability had earlier median ages of ASD diagnosis (43 months) than those without intellectual disability (53 months). INTERPRETATION: For 2020, one in 36 children aged 8 years (approximately 4% of boys and 1% of girls) was estimated to have ASD. These estimates are higher than previous ADDM Network estimates during 2000-2018. For the first time among children aged 8 years, the prevalence of ASD was lower among White children than among other racial and ethnic groups, reversing the direction of racial and ethnic differences in ASD prevalence observed in the past. Black children with ASD were still more likely than White children with ASD to have a co-occurring intellectual disability. PUBLIC HEALTH ACTION: The continued increase among children identified with ASD, particularly among non-White children and girls, highlights the need for enhanced infrastructure to provide equitable diagnostic, treatment, and support services for all children with ASD. Similar to previous reporting periods, findings varied considerably across network sites, indicating the need for additional research to understand the nature of such differences and potentially apply successful identification strategies across states.

        Maenner, M. J. Williams, A. R. Amoakohene, E. McArthur, D. Williams, S. Patrick, M. DiRienzo, M. Washington, A. Shaw, K. A.

      5. Early identification of autism spectrum disorder among children aged 4 years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020
        Shaw KA, Bilder DA, McArthur D, Williams AR, Amoakohene E, Bakian AV, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Pas ET, Salinas A, Warren Z, Williams S, Esler A, Grzybowski A, Ladd-Acosta CM, Patrick M, Zahorodny W, Green KK, Hall-Lande J, Lopez M, Mancilla KC, Nguyen RH, Pierce K, Schwenk YD, Shenouda J, Sidwell K, Vehorn A, DiRienzo M, Gutierrez J, Hallas L, Hudson A, Spivey MH, Pettygrove S, Washington A, Maenner MJ.
        MMWR Surveill Summ. 2023 ;72(1):1-15.
        PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2020. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2020, a total of 11 sites (located in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) conducted surveillance of ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2020. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in an evaluation, 2) a special education classification of autism (eligibility), or 3) an ASD International Classification of Diseases (ICD) code (revisions 9 or 10). Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had a documented qualified professional's statement indicating a suspicion of ASD. This report focuses on children aged 4 years in 2020 compared with children aged 8 years in 2020. RESULTS: For 2020, ASD prevalence among children aged 4 years varied across sites, from 12.7 per 1,000 children in Utah to 46.4 in California. The overall prevalence was 21.5 and was higher among boys than girls at every site. Compared with non-Hispanic White children, ASD prevalence was 1.8 times as high among Hispanic, 1.6 times as high among non-Hispanic Black, 1.4 times as high among Asian or Pacific Islander, and 1.2 times as high among multiracial children. Among the 58.3% of children aged 4 years with ASD and information on intellectual ability, 48.5% had an IQ score of ≤70 on their most recent IQ test or an examiner's statement of intellectual disability. Among children with a documented developmental evaluation, 78.0% were evaluated by age 36 months. Children aged 4 years had a higher cumulative incidence of ASD diagnosis or eligibility by age 48 months compared with children aged 8 years at all sites; risk ratios ranged from 1.3 in New Jersey and Utah to 2.0 in Tennessee. In the 6 months before the March 2020 COVID-19 pandemic declaration by the World Health Organization, there were 1,593 more evaluations and 1.89 more ASD identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. After the COVID-19 pandemic declaration, this pattern reversed: in the 6 months after pandemic onset, there were 217 fewer evaluations and 0.26 fewer identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. Patterns of evaluation and identification varied among sites, but there was not recovery to pre-COVID-19 pandemic levels by the end of 2020 at most sites or overall. For 2020, prevalence of suspected ASD ranged from 0.5 (California) to 10.4 (Arkansas) per 1,000 children aged 4 years, with an increase from 2018 at five sites (Arizona, Arkansas, Maryland, New Jersey, and Utah). Demographic and cognitive characteristics of children aged 4 years with suspected ASD were similar to children aged 4 years with ASD. INTERPRETATION: A wide range of prevalence of ASD by age 4 years was observed, suggesting differences in early ASD identification practices among communities. At all sites, cumulative incidence of ASD by age 48 months among children aged 4 years was higher compared with children aged 8 years in 2020, indicating improvements in early identification of ASD. Higher numbers of evaluations and rates of identification were evident among children aged 4 years until the COVID-19 pandemic onset in 2020. Sustained lower levels of ASD evaluations and identification seen at a majority of sites after the pandemic onset could indicate disruptions in typical practices in evaluations and identification for health service providers and schools through the end of 2020. Sites with more recovery could indicate successful strategies to mitigate service interruption, such as pivoting to telehealth approaches for evaluation. PUBLIC HEALTH ACTION: From 2016 through February of 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing ASD evaluation and identification 4 years earlier (from 2012 until March 2016) among the cohort of children aged 8 years in 2020 . From 2016 to March 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing that among children aged 8 years in 2020 from 2012 until March 2016. The disruptions in evaluation that coincided with the start of the COVID-19 pandemic and the increase in prevalence of suspected ASD in 2020 could have led to delays in ASD identification and interventions. Communities could evaluate the impact of these disruptions as children in affected cohorts age and consider strategies to mitigate service disruptions caused by future public health emergencies.

        Shaw, K. A. McArthur, D. Williams, A. R. Amoakohene, E. Hughes, M. M. Williams, S. Patrick, M. Green, K. K. DiRienzo, M. Washington, A. Maenner, M. J.

      6. Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveillance (CHAMPS), December 2016 -December 2021
        Mahtab S, Madhi SA, Baillie VL, Els T, Thwala BN, Onyango D, Tippet-Barr BA, Akelo V, Igunza KA, Omore R, Arifeen SE, Gurley ES, Alam M, Chowdhury AI, Rahman A, Bassat Q, Mandomando I, Ajanovic S, Sitoe A, Varo R, Sow SO, Kotloff KL, Badji H, Tapia MD, Traore CB, Ogbuanu IU, Bunn J, Luke R, Sannoh S, Swarray-Deen A, Assefa N, Scott JA, Madrid L, Marami D, Fentaw S, Diaz MH, Martines RB, Breiman RF, Madewell ZJ, Blau DM, Whitney CG.
        PLOS Glob Public Health. 2023 ;3(3):e0001612.
        Each year, 2.4 million children die within their first month of life. Child Health and Mortality Prevention Surveillance (CHAMPS) established in 7 countries aims to generate accurate data on why such deaths occur and inform prevention strategies. Neonatal deaths that occurred between December 2016 and December 2021 were investigated with MITS within 24-72 hours of death. Testing included blood, cerebrospinal fluid and lung cultures, multi-pathogen PCR on blood, CSF, nasopharyngeal swabs and lung tissue, and histopathology examination of lung, liver and brain. Data collection included clinical record review and family interview using standardized verbal autopsy. The full set of data was reviewed by local experts using a standardized process (Determination of Cause of Death) to identify all relevant conditions leading to death (causal chain), per WHO recommendations. For analysis we stratified neonatal death into 24-hours of birth, early (1-<7 days) and late (7-<28 days) neonatal deaths. We analyzed 1458 deaths, 41% occurring within 24-hours, 41% early and 18% late neonatal deaths. Leading underlying causes of death were complications of intrapartum events (31%), complications of prematurity (28%), infections (17%), respiratory disorders (11%), and congenital malformations (8%). In addition to the underlying cause, 62% of deaths had additional conditions and 14% had ≥3 other conditions in the causal chain. The most common causes considering the whole causal chain were infection (40%), prematurity (32%) and respiratory distress syndrome (28%). Common maternal conditions linked to neonatal death were maternal hypertension (10%), labour and delivery complications (8%), multiple gestation (7%), placental complications (6%) obstructed labour and chorioamnionitis (5%, each). CHAMPS' findings showing the full causal chain of events that lead to death, in addition to maternal factors, highlights the complexities involved in each death along with the multiple opportunities for prevention. Highlighting improvements to prenatal and obstetric care and infection prevention are urgently needed in high-mortality settings.

        Tippet-Barr, B. A. Akelo, V. Diaz, M. H. Martines, R. B. Madewell, Z. J. Blau, D. M.

      7. HIV retesting for pregnant and breastfeeding women across maternal child health services in Nampula, Mozambique
        Teasdale CA, Choy M, Tsiouris F, De Gusmao EP, Banqueiro EC, Couto A, Tibana K, Flowers N, Urso M, Vitale M, Abrams EJ.
        PLoS One. 2023 ;18(3):e0283558.
        BACKGROUND: Repeat HIV testing during pregnancy and breastfeeding identifies women with incident infections, those living with HIV who have been lost to care, and infants at risk for HIV infection. We report data from repeat testing for women in maternal and child health (MCH) services at 10 health facilities in Mozambique. METHODS: Routinely collected data from health facility registers are reported from April-November 2019. From antenatal care (ANC), we report numbers and proportions of women eligible for retesting; returned for care when retesting eligible; retested; and HIV-positive (HIV+) at retesting. From child welfare clinics (CWC), we report mothers retested; tested HIV-positive; HIV+ mothers linked to ART services; HIV-exposed infants (HEI) tested for HIV with polymerase chain reaction (PCR) tests; HEI testing PCR positive; PCR-positive infants linked to care. RESULTS: In ANC, 28,233 pregnant women tested HIV-negative at first ANC visit, 40.7% had a follow-up visit when retesting eligible, among whom 84.8% were retested and 0.3%(N = 26) tested HIV+. In CWC, 26,503 women were tested; 0.8%(N = 212) tested HIV+ and 74.1%(N = 157) of HIV+ women were linked to care. Among 157 HEI identified in CWC, 68.4%(N = 145) received PCR testing and 19.3%(N = 28) tested positive. CONCLUSION: In ANC, less than half of pregnant women eligible for retesting returned for follow-up visits, and test positivity was low among women retested in ANC and CWC. In CWC, linkage to infant testing was poor and almost 20% of HEI were PCR-positive. Implementing retesting for pregnant and breastfeeding women is challenging due to high numbers of women and low testing yield.

        Flowers, N. Urso, M.

    • Nutritional Sciences
      1. Accelerating action to reduce anemia: Review of causes and risk factors and related data needs
        Hess SY, Owais A, Jefferds ME, Young MF, Cahill A, Rogers LM.
        Ann N Y Acad Sci. 2023 .
        Anemia is a major public health concern. Young children, menstruating adolescent girls and women, and pregnant women are among the most vulnerable. Anemia is the consequence of a wide range of causes, including biological, socioeconomic, and ecological risk factors. Primary causes include: iron deficiency; inherited red blood cell disorders; infections, such as soil-transmitted helminthiasis, schistosomiasis, and malaria; gynecological and obstetric conditions; and other chronic diseases that lead to blood loss, decreased erythropoiesis, or destruction of erythrocytes. The most vulnerable population groups in low- and middle-income countries are often at the greatest risk to suffer from several of these causes simultaneously as low socioeconomic status is linked with an increased risk of anemia through multiple pathways. Targeted and effective action is needed to prevent anemia. Understanding the causes and risk factors of anemia for different population subgroups within a country guides the design and implementation of effective strategies to prevent and treat anemia. A coordinated approach across various expert groups and programs could make the best use of existing data or could help to determine when newer and more relevant data may need to be collected, especially in countries with a high anemia burden and limited information on the etiology of anemia.

        Jefferds, M. E. D.

    • Occupational Safety and Health
      1. Industry, occupation, and exposure history of mesothelioma patients in the U.S. National Mesothelioma Virtual Bank, 2006-2022
        Gao Y, Mazurek JM, Li Y, Blackley D, Weissman DN, Burton SV, Amin W, Landsittel D, Becich MJ, Ye Y.
        Environ Res. 2022 :115085.
        BACKGROUND: Malignant mesothelioma is associated with environmental and occupational exposure to certain mineral fibers, especially asbestos. This study aims to examine work histories of mesothelioma patients and their survival time. METHOD: Using the NIOSH Industry and Occupation Computerized Coding System, we mapped occupations and industries recorded for 748 of 1444 patients in the U.S. National Mesothelioma Virtual Bank (NMVB) during the period 2006-2022. Descriptive and survival analyses were conducted. RESULTS: Among the 1023 industries recorded for those having mesothelioma, the most frequent cases were found for those in manufacturing (n = 225, 22.0%), construction (138, 13.5%), and education services (66, 6.5%); among the 924 occupation records, the most frequent cases were found for those in construction and extraction (174, 18.8%), production (145, 15.7%), and management (84, 9.1%). Males (583) or persons aged >40 years (658) at the time of diagnosis tended to have worked in industries traditionally associated with mesothelioma (e.g., construction), while females (163) or persons aged 20-40 years (27) tended to have worked in industries not traditionally associated with mesothelioma (e.g., health care). Asbestos, unknown substances, and chemical solvents were the most frequently reported exposure, with females most often reporting an unknown substance. A multi-variable Cox Hazard Regression analysis showed that significant prognostic factors associated with decreased survival in mesothelioma cases are sex (male) and work experience in utility-related industry, while factor associated with increased survival are epithelial or epithelioid histological type, prior history of surgery and immunotherapy, and industry experience in accommodation and food services. CONCLUSION: The NMVB has the potential of serving as a sentinel surveillance mechanism for identifying industries and occupations not traditionally associated with mesothelioma. Results indicate the importance of considering all potential sources of asbestos exposures including occupational, environmental, and extra-occupational exposures when evaluating mesothelioma patients and advising family members.

        Mazurek, J. M. Blackley, D. Weissman, D. N. Burton, S. V.

      2. Utilizing Haddon matrix to assess nonfatal commercial fishing injury factors in Oregon and Washington
        Doza S, Bovbjerg V, Case S, Vaughan A, Kincl L.
        Inj Epidemiol. 2023 ;10(1):18.
        BACKGROUND: Commercial fishing is a precarious industry with high fatal and nonfatal injury rates. The Risk Information System of Commercial [RISC] Fishing project at Oregon State University has been tracking both fatal and nonfatal injuries among Oregon and Washington commercial fishermen. We examined the utility of the RISC dataset variables in highlighting injury factors and prevention opportunities. METHOD: We identified 245 nonfatal commercial fishing injuries in Oregon and Washington (2000-2018) and assessed the top three injury events (contact with objects or equipment, transportation incidents, and slips/trips/falls) using a cross-sectional design. We generated a Haddon matrix for each event type and populated the matrices with injury-associated factors following our a-priori matrix. RESULTS: We observed 108 nonfatal injuries due to contact with objects. Contact injuries occurred during fishing (40%) with fishing gears (40%), often while hauling the fishing gear (22%). Common injury mechanisms included getting caught in running equipment or machinery (19%) or compressed by shifting objects or equipment (18%). Of the 58 transportation injuries most occurred in catchers (93%) and smaller vessels (1 to 3 crew) (55%). Vessel casualties were common as several vessels struck rocks/bottom (29%) or experienced fire and explosion (19%). The crew was abandoned to water (38%), often due to no raft or raft malfunctions (19%). Slip/trip/fall injuries (n = 43) typically happened during onboard traffic (49%). Such events were largely experienced by the catcher-processors (44%) including large vessels with > 100 crew (28%). CONCLUSION: The Haddon matrix demonstrated the injury-event timeline and helped to identify potential injury-associated factors. Our injury-specific risk matrices will let commercial fishing stakeholders determine priorities and work with the experts on prevention efforts.

        Case, S.

      3. Establishment-level occupational safety analytics: Challenges and opportunities
        Foreman AM, Friedel JE, Ludwig TD, Ezerins ME, Açikgöz Y, Bergman SM, Wirth O.
        Int J Ind Ergon. 2023 ;94.
        In occupational safety and health, big data and analytics show promise for the prediction and prevention of workplace injuries. Advances in computing power and analytical methods have allowed companies to reveal insights from the “big” data that previously would have gone undetected. Despite the promise, occupational safety has lagged behind other industries, such as supply chain management and healthcare, in terms of exploiting the potential of analytics and much of the data collected by organizations goes unanalyzed. The purpose of the present paper is to argue for the broader application of establishment-level safety analytics. This is accomplished by defining the terms, describing previous research, outlining the necessary components required, and describing knowledge gaps and future directions. The knowledge gaps and future directions for research in establishment-level analytics are categorized into readiness for analytics, analytics methods, technology integration, data culture, and impact of analytics. © 2023

        Foreman, A. M. Friedel, J. E. Wirth, O.

      4. Working alone and/or in remote locations: Opportunities to prevent the risk of fatality from cardiovascular events in oil and gas extraction workers
        Zimmerman SM, Scott KA, Wingate KC, Ramirez-Cardenas A, Pompei R, Hagan-Haynes K, Hill R, Wood E.
        J Occup Environ Med. 2023 .
        OBJECTIVE: Explore personal and work factors related to fatal cardiac events among oil and gas extraction (OGE) workers. METHODS: The NIOSH Fatalities in Oil and Gas Extraction database was reviewed to identify fatal cardiac events among OGE workers from 2014 through 2019. A case series design was used to review case files, provide descriptive statistics, and summarize the findings. RESULTS: There were 75 fatalities identified, including 55 (73%) with sufficient information for review. Of the 55 workers, 18 (33%) worked alone. Thirty-six (66%) fatal cardiac events were unwitnessed by a co-worker. Toxicology findings suggested some possible exposures to hydrogen sulfide or hydrocarbon gases or vapors. Missing data was common. CONCLUSION: This study identified the need for cardiovascular disease prevention and treatment, emergency preparedness, lone worker programs, medical screening, and enhanced exposure control in the OGE industry.

        Scott, K. A. Wingate, K. C. Ramirez-Cardenas, A. Hagan-Haynes, K. Hill, R.

      5. Workers’ compensation injury claims among firefighters in Ohio, 2001–2017
        Quinn TD, Marsh SM, Oldham K, Wurzelbacher SJ, Naber SJ.
        J Saf Res. 2023 .
        Background: Firefighters are at high risk for nonfatal and fatal occupational injuries. While some past research has quantified firefighter injuries using various data sources, Ohio workers’ compensation injury claims data largely have not been used. Methods: Public and private firefighter claims, including volunteer and career firefighters, from Ohio's workers’ compensation data for 2001–2017 were identified based on occupational classification codes and manual review of the occupation title and injury description. The task during injury (firefighting, patient care, training, other/unknown, etc.) was manually coded based on the injury description. Injury claim counts and proportions were described across claim type (medical-only or lost-time), worker demographics, task during injury, injury events, and principal diagnoses. Results: 33,069 firefighter claims were identified and included. Most claims were medical-only (66.28%, <8 days away from work) and involved males (93.81%) aged 25-54 years (86.54%). While the task during injury could not be categorized for many narratives (45.96%), the largest percentage that could be categorized occurred during firefighting (20.48%) and patient care (17.60%). The most common injury events were overexertion involving outside sources (31.33%) and struck by objects or equipment (12.68%). The most frequent principal diagnoses were back, lower extremity, and upper extremity sprains (16.02%, 14.46%, and 11.98%, respectively). Conclusions: This study provides a preliminary basis for the development of focused firefighter injury prevention programming and training. Obtaining denominator data, enabling rate calculation, would strengthen the risk characterization. Based on the current data, prevention efforts focusing on the most frequent injury events and diagnoses may be warranted. © 2023 National Safety Council and Elsevier Ltd

        Quinn, T. D. Marsh, S. M. Oldham, K. Wurzelbacher, S. J.

    • Parasitic Diseases
      1. Durability of long-lasting insecticidal nets (LLINs) in Ethiopia
        Hiruy HN, Irish SR, Abdelmenan S, Wuletaw Y, Zewde A, Woyessa A, Haile M, Chibsa S, Lorenz L, Worku A, Yukich J, Berhane Y, Keating J.
        Malar J. 2023 ;22(1):109.
        BACKGROUND: The functional survival time of long-lasting insecticidal nets (LLINs), which varies across different field contexts, is critical for the successful prevention of malaria transmission. However, there is limited data on LLIN durability in field settings in Ethiopia. METHODS: A three-year longitudinal study was conducted to monitor attrition, physical integrity, and bio-efficacy and residual chemical concentration of LLINs in four regions in Ethiopia. World Health Organization (WHO) guidelines were used to determine sample size, measure physical integrity, and calculate attrition rates, and functional survival time. Yearly bio-efficacy testing was done on randomly selected LLINs. An excel tool developed by vector works project was used to calculate the median functional survival time of the LLINs. Predictors of functional survival were identified by fitting binary and multivariate cox proportional hazards model. RESULTS: A total of 3,396 LLINs were included in the analysis. A total of 3,396 LLINs were included in the analysis. By the end of 36 months, the proportion of LLINs functionally surviving was 12.9% [95% confidence interval (CI) 10.5, 15.6], the rates of attrition due to physical damage and repurposing were 48.8% [95% confidence interval (CI) 45.0, 52.6] and 13.8% [95% confidence interval (CI) 11.6, 14.6], respectively. The estimated median functional survival time was 19 months (95%CI 17, 21). Factors associated with shorter functional survival time include being in a low malaria transmission setting [Adjusted Hazards Ratio (AHR) (95%CI) 1.77 (1.22, 2.55)], rural locations [AHR (95%CI) 1.83 (1.17, 2.84)], and in a room where cooking occurs [AHR (95%CI) 1.28 (1.05, 1.55)]. Bioassay tests revealed that 95.3% (95%CI 86.4, 98.5) of the LLINs met the WHO criteria of bio-efficacy after 24 months of distribution. CONCLUSION: The LLIN survival time was shorter than the expected three years due to high attrition rates and rapid loss of physical integrity. National malaria programmes may consider, procuring more durable LLINs, educating communities on how to prevent damage of LLINs, and revising the current three-year LLIN distribution schedule to ensure sufficient protection is provided by LLINs against malaria transmission. While this paper contributes to the understanding of determinants impacting functional survival, further research is needed to understand factors for the rapid attrition rates and loss of physical integrity of LLINs in field settings.

        Irish, S. R.

    • Physical Activity
      1. Association between passively collected walking and bicycling data and purposefully collected active commuting survey data-United States, 2019
        Soto GW, Webber BJ, Fletcher K, Chen TJ, Garber MD, Smith A, Wilt G, Conn M, Whitfield GP.
        Health Place. 2023 ;81:103002.
        Commercially-available location-based services (LBS) data derived primarily from mobile devices may provide an alternative to surveys for monitoring physically-active transportation. Using Spearman correlation, we compared county-level metrics of walking and bicycling from StreetLight with metrics of physically-active commuting among U.S. workers from the American Community Survey. Our strongest pair of metrics ranked counties (n = 298) similarly for walking (rho = 0.53 [95% CI: 0.44-0.61]) and bicycling (rho = 0.61 [0.53-0.67]). Correlations were higher for denser and more urban counties. LBS data may offer public health and transportation professionals timely information on walking and bicycling behavior at finer geographic scales than some existing surveys.

        Soto, G. W. Webber, B. J. Fletcher, K. Chen, T. J. Garber, M. D. Smith, A. Wilt, G. Conn, M. Whitfield, G. P.

    • Public Health Leadership and Management

    • Substance Use and Abuse
      1. IMPORTANCE: Federal emergency authorities were invoked during the COVID-19 pandemic to expand clinical telehealth for opioid use disorder (OUD). OBJECTIVE: To examine the association of the receipt of telehealth services and medications for OUD (MOUD) with fatal drug overdoses before and during the pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used exploratory longitudinal data from 2 cohorts (prepandemic cohort: September 1, 2018, to February 29, 2020; pandemic cohort: September 1, 2019, to February 28, 2021) of Medicare Fee-for-Service beneficiaries aged 18 years or older initiating an episode of OUD-related care using Medicare Fee-for-Service data from the Centers for Medicare & Medicaid Services and National Death Index data from the Centers for Disease Control and Prevention. Data analysis was performed from September 19 to October 17, 2022. EXPOSURES: Prepandemic vs pandemic cohort demographic, medical, substance use, and psychiatric characteristics. MAIN OUTCOMES AND MEASURES: Receipt of OUD-related telehealth services, receipt of MOUD, and fatal drug overdose. RESULTS: The prepandemic cohort comprised 105 162 beneficiaries (58.1% female; 67.6% aged 45-74 years). The pandemic cohort comprised 70 479 beneficiaries (57.1% female; 66.3% aged 45-74 years). The rate of all-cause mortality was higher in the pandemic cohort (99.9 per 1000 beneficiaries; 7041 deaths) than in the prepandemic cohort (76.8 per 1000; 8076 deaths) (P < .001). The rate of fatal drug overdoses was higher in the pandemic cohort (5.1 per 1000 beneficiaries; n = 358) than in the prepandemic cohort (3.7 per 1000; n = 391) (P < .001). The percentage of deaths due to a fatal drug overdose was similar in the prepandemic (4.8%) and pandemic (5.1%) cohorts (P = .49). In multivariable analysis of the pandemic cohort, receipt of OUD-related telehealth was associated with a significantly lower adjusted odds ratio (aOR) for fatal drug overdose (aOR, 0.67; 95% CI, 0.48-0.92) as was receipt of MOUD from opioid treatment programs (aOR, 0.41; 95% CI, 0.25-0.68) and receipt of buprenorphine in office-based settings (aOR, 0.62; 95% CI, 0.43-0.91) compared with those not receiving MOUD; receipt of extended-release naltrexone in office-based settings was not associated with lower odds for fatal drug overdose (aOR, 1.16; 95% CI, 0.41-3.26). CONCLUSIONS AND RELEVANCE: This cohort study found that, among Medicare beneficiaries initiating OUD-related care during the COVID-19 pandemic, receipt of OUD-related telehealth services was associated with reduced risk for fatal drug overdose, as was receipt of MOUD from opioid treatment programs and receipt of buprenorphine in office-based settings. Strategies to expand provision of MOUD, increase retention in care, and address co-occurring physical and behavioral health conditions are needed.

        Jones, C. M. Losby, J. L.

      2. Methods for jurisdictional vulnerability assessment of opioid-related outcomes
        Shrestha S, Bayly R, Pustz J, Sawyer J, Van Handel M, Lingwall C, Stopka TJ.
        Prev Med. 2023 ;170:107490.
        In 2020, an estimated 2.7 million people in the US had opioid use disorder, increasing their risk of opioid-related morbidity and mortality. While jurisdictional vulnerability assessments (JVA) of opioid-related outcomes have been conducted previously in the US, there has been no unifying methodological framework. Between 2019 and 2021, we prepared ten JVAs, in collaboration with the Council of State and Territorial Epidemiologists, the Centers for Disease Control and Prevention, and state public health agencies, to evaluate the risk for opioid-involved overdose (OOD) fatalities and related consequences. Our aim is to share the framework we developed for these ten JVAs, based on our study of the work of Van Handel et al. from 2016, as well as a summary of 18 publicly available assessments of OOD or associated hepatitis C virus infection vulnerability. We developed a three-tiered framework that can be applied by jurisdictions based on the number of units of analysis (e.g., counties, ZIP Codes, census tracts): under 10 (Tier 1), 10 to <50 (Tier 2), and 50 or more (Tier 3). We calculated OOD vulnerability indices based on variable ranks, weighted variable ranks, or multivariable regressions, respectively, for the three tiers. We developed thematic maps, conducted spatial analyses, and visualized service provider locations, drive-time service areas, and service accessibility relative to OOD risk. The methodological framework and examples of our findings from several jurisdictions can be used as a foundation for future assessments and help inform policies to mitigate the impact of the opioid overdose crisis.

        Van Handel, M.

    • Veterinary Medicine
      1. Fatal systemic fungal infection in eastern bongo antelope (Tragelaphus eurycerus isaaci): Six cases
        Garner MM, Fredholm DV, Citino SB, Keating MK, Ritter JM, Lockart S, Lysen C, Bradway DS, Koons AR, Newton J.
        J Zoo Wildl Med. 2023 ;54(1):102-110.
        Over a span of 6 yr, six adult eastern bongo antelope (Tragelaphus eurycerus isaaci) from a single institution died due to systemic mycotic infections. All animals were of the same genetic lineage and in good body condition at the time of death. Gross findings in all cases included multifocal white-to-tan nodules up to 10 cm in diameter that were most numerous in the heart, lung, and kidney. Histologic examination identified these nodules as foci of granulomatous inflammation containing branching, septate, broad, undulating fungal elements. Identification of the fungal species was pursued using PCR with sequencing, immunohistochemistry, and culture. Multiple fungal species were identified using the various modalities, and commonality of species identification was limited to Cladosporium sp. in four of the cases. The clinical and postmortem findings in these cases were identical and were considered to be the same infectious disease. The Cladosporium sp. was considered a candidate as an emerging fatal infectious agent in this population of bongo antelopes. In all of these cases, death was attributed to conduction abnormalities associated with the cardiac lesions or euthanasia.

        Keating, M. K. Ritter, J. M. Lockart, S. Lysen, C.

    • Zoonotic and Vectorborne Diseases
      1. Fatal human rabies infection with suspected host-mediated failure of post-exposure prophylaxis following a recognized zoonotic exposure-Minnesota, 2021
        Holzbauer SM, Schrodt CA, Prabhu RM, Asch-Kendrick RJ, Ireland M, Klumb C, Firestone MJ, Liu G, Harry K, Ritter JM, Levine MZ, Orciari LA, Wilkins K, Yager P, Gigante CM, Ellison JA, Zhao H, Niezgoda M, Li Y, Levis R, Scott D, Satheshkumar PS, Petersen BW, Rao AK, Bell WR, Bjerk SM, Forrest S, Gao W, Dasheiff R, Russell K, Pappas M, Kiefer J, Bickler W, Wiseman A, Jurantee J, Reichard RR, Smith KE, Lynfield R, Scheftel J, Wallace RM, Bonwitt J.
        Clin Infect Dis. 2023 .
        BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

        Holzbauer, S. M. Schrodt, C. A. Ritter, J. M. Levine, M. Z. Orciari, L. A. Wilkins, K. Yager, P. Gigante, C. M. Ellison, J. A. Zhao, H. Niezgoda, M. Satheshkumar, P. S. Petersen, B. W. Rao, A. K. Wallace, R. M. Bonwitt, J.

      2. Structural elucidation of a protective B cell epitope on outer surface protein C (OspC) of the Lyme disease spirochete, borreliella Burgdorferi
        Rudolph MJ, Davis SA, Haque HM, Weis DD, Vance DJ, Piazza CL, Ejemel M, Cavacini L, Wang Y, Mbow ML, Gilmore RD, Mantis NJ.
        mBio. 2023 :e0298122.
        Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5's epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here, we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspC(A)). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC's α-helix 1 and α-helix 6, as well as interactions with the loop between α-helices 5 and 6. In addition, B5's complementarity-determining region (CDR) H3 bridged the OspC-OspC' homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspC(A). This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease. IMPORTANCE The spirochete Borreliella burgdorferi is a causative agent of Lyme disease, the most common tickborne disease in the United States. The spirochete is transmitted to humans during the course of a tick taking a bloodmeal. After B. burgdorferi is deposited into the skin of a human host, it replicates locally and spreads systemically, often resulting in clinical manifestations involving the central nervous system, joints, and/or heart. Antibodies directed against B. burgdorferi's outer surface protein C (OspC) are known to block tick-to-host transmission, as well as dissemination of the spirochete within a mammalian host. In this report, we reveal the first atomic structure of one such antibody in complex with OspC. Our results have implications for the design of a Lyme disease vaccine capable of interfering with multiple stages in B. burgdorferi infection.

        Mbow, M. L. Gilmore, R. D.

      3. A serological assay to detect and differentiate rodent exposure to soft tick and hard tick relapsing fever infections in the United States
        Parise CM, Bai Y, Brandt KS, Ford SL, Maes S, Replogle AJ, Kneubehl AR, Lopez JE, Eisen RJ, Hojgaard A.
        Ticks Tick Borne Dis. 2023 ;14(4):102167.
        Human cases of relapsing fever (RF) in North America are caused primarily by Borrelia hermsii and Borrelia turicatae, which are spread by argasid (soft) ticks, and by Borrelia miyamotoi, which is transmitted by ixodid (hard) ticks. In some regions of the United States, the ranges of the hard and soft tick RF species are known to overlap; in many areas, recorded ranges of RF spirochetes overlap with Lyme disease (LD) group Borrelia spirochetes. Identification of RF clusters or cases detected in unusual geographic localities might prompt public health agencies to investigate environmental exposures, enabling prevention of additional cases through locally targeted mitigation. However, exposure risks and mitigation strategies differ among hard and soft tick RF, prompting a need for additional diagnostic strategies that differentiate hard tick from soft tick RF. We evaluated the ability of new and previously described recombinant antigens in serological assays to differentiate among prior exposures in mice to LD, soft or hard tick RF spirochetes. We extracted whole-cell protein lysates from RF Borrelia cultures and synthesized six recombinant RF antigens (Borrelia immunogenic protein A (BipA) derived from four species of RF Borrelia, glycerophosphodiester phosphodiesterase (GlpQ), and Borrelia miyamotoi membrane antigen A (BmaA)) to detect reactivity in laboratory derived (Peromyscus sp. and Mus sp.) mouse serum infected with RF and LD Borrelia species. Among 44 Borrelia exposed mouse samples tested, all five mice exposed to LD spirochetes were correctly differentiated from the 39 mice exposed to RF Borrelia using the recombinant targets. Of the 39 mice exposed to RF spirochetes, 28 were accurately categorized to species of exposure (71%). Segregation among soft tick RF species (Borrelia hermsii, Borrelia parkeri and Borrelia turicatae) was inadequate (58%) owing to observed cross-reactivity among recombinant BipA protein targets. However, among the 28 samples accurately separated to species, all were accurately assigned to soft tick or hard tick RF type. Although not adequately specific to accurately categorize exposure to soft tick RF species, the recombinant BipA protein targets from soft and hard tick RF species show utility in accurately discriminating mouse exposures to LD or RF Borrelia, and accurately segregate hard tick from soft tick RF Borrelia exposure.

        Bai, Y. Brandt, K. S. Ford, S. L. Maes, S. Replogle, A. J. Eisen, R. J. Hojgaard, A.


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