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Issue 17, April 26, 2022

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CDC Science Clips: Volume 14, Issue 17, April 26, 2022

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

The report consists of these components:

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Communicable Diseases
      1. INTRODUCTION: Neisseria gonorrhoeae has developed resistance to all first-line recommended therapies, making gonococcal antimicrobial resistance a major public health concern given limited antibiotic options currently and an even smaller antimicrobial development pipeline. Since the release of the Centers for Disease Control and Prevention (CDC) 2015 STD Treatment Guidelines, azithromycin, part of the 2015 dual-drug treatment regimen, has had a rapid rise in resistance. The 2020 CDC Gonorrhea Treatment Recommendations and the 2021 Sexually Transmitted Infections (STI) Treatment Guidelines were developed weighing the priorities of treating the individual, protecting the population, and preventing antimicrobial resistance. METHODS: Gonorrhea subject matter experts (SME) generated 8 key questions and conducted a literature review of updated data from 2013 to 2019 on gonorrhea antimicrobial resistance, treatment failures, clinical trials, and other key topics. More than 2200 abstracts were assessed, and 248 clinically relevant articles were thoroughly reviewed. SMEs also evaluated N gonorrhoeae antimicrobial resistance data from the Gonococcal Isolate Surveillance Project (GISP). EVIDENCE: Although there have been reports of ceftriaxone treatment failures internationally, GISP data suggest that ceftriaxone minimal inhibitory concentrations (MICs) have remained stable in the United States, with < 0.1% exhibiting an "alert value" MIC (> 0.25 mcg/mL). However, GISP documented a rapid rise in the proportion of isolates with an elevated MIC (≥ 2.0 mcg/mL) to azithromycin-nearly 5% in 2018. At the same time, new pharmacokinetic/pharmacodynamic data are available, and there is greater recognition of the need for antimicrobial stewardship. SUMMARY: The 2021 CDC STI Treatment Guidelines now recommend 500mg ceftriaxone intramuscularly once for the treatment of uncomplicated gonorrhea at all anatomic sites. If coinfection with chlamydia has not been excluded, cotreatment with doxycycline 100mg twice daily for 7 days should be added. Few alternative therapies exist for persons with cephalosporin allergies; there are no recommended alternative therapies for N gonorrhoeae infection of the throat.

      2. Genital herpes, caused by herpes simplex virus (HSV) type 1 or type 2, is a prevalent sexually transmitted infection (STI). Given that HSV is an incurable infection, there are important concerns about appropriate use of diagnostic tools, management of infection, prevention of transmission to sexual partners, and appropriate counseling. In preparation for updating the Centers for Disease Control and Prevention (CDC) STI treatment guidelines, key questions for management of genital herpes infection were developed with a panel of experts. To answer these questions, a systematic literature review was performed, with tables of evidence including articles that would change guidance assembled. These data were used to inform recommendations in the 2021 CDC STI treatment guidelines.

      3. Diagnosis and management of trichomonas vaginalis: Summary of evidence reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelinesexternal icon
        Kissinger PJ, Gaydos CA, Seña AC, Scott McClelland R, Soper D, Secor WE, Legendre D, Workowski KA, Muzny CA.
        Clin Infect Dis. 2022 Apr 13;74(Supplement_2):S152-s161.
        Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

      4. Enteric infections in men who have sex with menexternal icon
        McNeil CJ, Kirkcaldy RD, Workowski K.
        Clin Infect Dis. 2022 Apr 13;74(Supplement_2):S169-s178.
        BACKGROUND: Enteric pathogens are often associated with exposure to food, water, animals, and feces from infected individuals. However, in sexual networks of men who have sex with men (MSM), transmission of enteric pathogens may occur during direct or indirect oral-anal contact. METHODS: We performed a scoping review of the literature for studies prior to July 2019 with key terms for gastrointestinal syndromes ("proctitis," "enteritis," "proctocolitis"), enteric pathogens or sexually transmitted infections (STIs), and outbreaks using multiple electronic databases. RESULTS: We identified 5861 records through database searches, bibliography reviews, and keyword searches, of which 117 references were included in the pathogen-specific reviews. CONCLUSIONS: The strength of observational data describing enteric pathogens in MSM and possible sexual transmission of enteric pathogens varies by pathogen; however, a robust body of literature describes the sexual transmission of Campylobacter, Giardia lamblia, and Shigella (particularly antimicrobial-resistant strains) in sexual networks of MSM. Providers are encouraged to consider enteritis or proctocolitis in MSM as possibly having been sexually transmitted and encourage targeted STI testing. Risk/harm reduction and prevention messages should also be incorporated, though there is an acknowledged paucity of evidence with regards to effective strategies. Further research is needed to understand the transmission and prevention of enteric pathogens in MSM.

      5. Diagnosis and management of bacterial vaginosis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelinesexternal icon
        Muzny CA, Balkus J, Mitchell C, Sobel JD, Workowski K, Marrazzo J, Schwebke JR.
        Clin Infect Dis. 2022 Apr 13;74(Supplement_2):S144-s151.
        In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed.

      6. Prevalence and management of sexually transmitted infections in correctional settings: A systematic reviewexternal icon
        Spaulding AC, Rabeeah Z, Del Mar González-Montalvo M, Akiyama MJ, Baker BJ, Bauer HM, Gibson BR, Nijhawan AE, Parvez F, Wangu Z, Chan PA.
        Clin Infect Dis. 2022 Apr 13;74(Supplement_2):S193-s217.
        Admissions to jails and prisons in the United States number 10 million yearly; persons entering locked correctional facilities have high prevalence of sexually transmitted infections (STIs). These individuals come disproportionately from communities of color, with lower access to care and prevention, compared with the United States as a whole. Following PRISMA guidelines, the authors present results of a systematic review of literature published since 2012 on STIs in US jails, prisons, Immigration and Customs Enforcement detention centers, and juvenile facilities. This updates an earlier review of STIs in short-term facilities. This current review contributed to new recommendations in the Centers for Disease Control and Prevention 2021 treatment guidelines for STIs, advising screening for Trichomonas in women entering correctional facilities. The current review also synthesizes recommendations on screening: in particular, opt-out testing is superior to opt-in protocols. Carceral interventions-managing diagnosed cases and preventing new infections from occurring (eg, by initiating human immunodeficiency virus preexposure prophylaxis before release)-can counteract structural racism in healthcare.

      7. Centers for Disease Control and Prevention's Sexually Transmitted Diseases Infection Guidelinesexternal icon
        Workowski KA, Bachmann LH.
        Clin Infect Dis. 2022 Apr 13;74(Supplement_2):S89-s94.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship

      2. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysisexternal icon
        Walker TM, Fowler PW, Knaggs J, Hunt M, Peto TE, Walker AS, Crook DW, Walker TM, Miotto P, Cirillo DM, Köser CU, Knaggs J, Iqbal Z, Hunt M, Chindelevitch L, Farhat MR, Comas I, Comas I, Posey J, Omar SV, Peto TE, Walker AS, Crook DW, Suresh A, Uplekar S, Laurent S, Colman RE, Rodwell TC, Nathanson CM, Zignol M, Ismail N, Rodwell TC, Walker AS, Steyn AJ, Lalvani A, Baulard A, Christoffels A, Mendoza-Ticona A, Trovato A, Skrahina A, Lachapelle AS, Brankin A, Piatek A, Gibertoni Cruz A, Koch A, Cabibbe AM, Spitaleri A, Brandao AP, Chaiprasert A, Suresh A, Barbova A, Van Rie A, Ghodousi A, Bainomugisa A, Mandal A, Roohi A, Javid B, Zhu B, Letcher B, Rodrigues C, Nimmo C, Nathanson CM, Duncan C, Coulter C, Utpatel C, Liu C, Grazian C, Kong C, Köser CU, Wilson DJ, Cirillo DM, Matias D, Jorgensen D, Zimenkov D, Chetty D, Moore DA, Clifton DA, Crook DW, van Soolingen D, Liu D, Kohlerschmidt D, Barreira D, Ngcamu D, Santos Lazaro ED, Kelly E, Borroni E, Roycroft E, Andre E, Böttger EC, Robinson E, Menardo F, Mendes FF, Jamieson FB, Coll F, Gao GF, Kasule GW, Rossolini GM, Rodger G, Smith EG, Meintjes G, Thwaites G, Hoffmann H, Albert H, Cox H, Laurenson IF, Comas I, Arandjelovic I, Barilar I, Robledo J, Millard J, Johnston J, Posey J, Andrews JR, Knaggs J, Gardy J, Guthrie J, Taylor J, Werngren J, Metcalfe J, Coronel J, Shea J, Carter J, Pinhata JM, Kus JV, Todt K, Holt K, Nilgiriwala KS, Ghisi KT, Malone KM, Faksri K, Musser KA, Joseph L, Rigouts L, Chindelevitch L, Jarrett L, Grandjean L, Ferrazoli L, Rodrigues M, Farhat M, Schito M, Fitzgibbon MM, Loembé MM, Wijkander M, Ballif M, Rabodoarivelo MS, Mihalic M, Wilcox M, Hunt M, Zignol M, Merker M, Egger M, O'Donnell M, Caws M, Wu MH, Whitfield MG, Inouye M, Mansjö M, Dang Thi MH, Joloba M, Kamal SM, Okozi N, Ismail N, Mistry N, Hoang NN, Rakotosamimanana N, Paton NI, Rancoita PM, Miotto P, Lapierre P, Hall PJ, Tang P, Claxton P, Wintringer P, Keller PM, Thai PV, Fowler PW, Supply P, Srilohasin P, Suriyaphol P, Rathod P, Kambli P, Groenheit R, Colman RE, Ong RT, Warren RM, Wilkinson RJ, Diel R, Oliveira RS, Khot R, Jou R, Tahseen S, Laurent S, Gharbia S, Kouchaki S, Shah S, Plesnik S, Earle SG, Dunstan S, Hoosdally SJ, Mitarai S, Gagneux S, Omar SV, Yao SY, Grandjean Lapierre S, Battaglia S, Niemann S, Pandey S, Uplekar S, Halse TA, Cohen T, Cortes T, Prammananan T, Kohl TA, Thuong NT, Teo TY, Peto TE, Rodwell TC, William T, Walker TM, Rogers TR, Surve U, Mathys V, Furió V, Cook V, Vijay S, Escuyer V, Dreyer V, Sintchenko V, Saphonn V, Solano W, Lin WH, van Gemert W, He W, Yang Y, Zhao Y, Qin Y, Xiao YX, Hasan Z, Iqbal Z, Puyen ZM, CryPtic Consortium t, Treat C.
        Lancet Microbe. 2022 ;3(4):e265-e273.
        Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

    • Chronic Diseases and Conditions
      1. The small HDL particle hypothesis of Alzheimer's diseaseexternal icon
        Martinez AE, Weissberger G, Kuklenyik Z, He X, Meuret C, Parekh T, Rees JC, Parks BA, Gardner MS, King SM, Collier TS, Harrington MG, Sweeney MD, Wang X, Zlokovic BV, Joe E, Nation DA, Schneider LS, Chui HC, Barr JR, Han SD, Krauss RM, Yassine HN.
        Alzheimers Dement. 2022 Apr 13.
        We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

      2. The use of electronic health records to inform cancer surveillance efforts: a scoping review and test of indicators for public health surveillance of cancer prevention and controlexternal icon
        Conderino S, Bendik S, Richards TB, Pulgarin C, Chan PY, Townsend J, Lim S, Roberts TR, Thorpe LE.
        BMC Med Inform Decis Mak. 2022 Apr 6;22(1):91.
        INTRODUCTION: State cancer prevention and control programs rely on public health surveillance data to set objectives to improve cancer prevention and control, plan interventions, and evaluate state-level progress towards achieving those objectives. The goal of this project was to evaluate the validity of using electronic health records (EHRs) based on common data model variables to generate indicators for surveillance of cancer prevention and control for these public health programs. METHODS: Following the methodological guidance from the PRISMA Extension for Scoping Reviews, we conducted a literature scoping review to assess how EHRs are used to inform cancer surveillance. We then developed 26 indicators along the continuum of the cascade of care, including cancer risk factors, immunizations to prevent cancer, cancer screenings, quality of initial care after abnormal screening results, and cancer burden. Indicators were calculated within a sample of patients from the New York City (NYC) INSIGHT Clinical Research Network using common data model EHR data and were weighted to the NYC population using post-stratification. We used prevalence ratios to compare these estimates to estimates from the raw EHR of NYU Langone Health to assess quality of information within INSIGHT, and we compared estimates to results from existing surveillance sources to assess validity. RESULTS: Of the 401 identified articles, 15% had a study purpose related to surveillance. Our indicator comparisons found that INSIGHT EHR-based measures for risk factor indicators were similar to estimates from external sources. In contrast, cancer screening and vaccination indicators were substantially underestimated as compared to estimates from external sources. Cancer screenings and vaccinations were often recorded in sections of the EHR that were not captured by the common data model. INSIGHT estimates for many quality-of-care indicators were higher than those calculated using a raw EHR. CONCLUSION: Common data model EHR data can provide rich information for certain indicators related to the cascade of care but may have substantial biases for others that limit their use in informing surveillance efforts for cancer prevention and control programs.


      4. Do medication prescription patterns follow guidelines in a cohort of women with interstitial cystitis/bladder pain syndrome?external icon
        Tholemeier LN, Bresee C, De Hoedt AM, Barbour KE, Kim J, Freedland SJ, Anger JT.
        Neurourol Urodyn. 2022 Apr 7.
        OBJECTIVE: To describe prescription prevalence of oral bladder pain medications among women with interstitial cystitis/bladder pain syndrome (IC/BPS) and to compare with current treatment guidelines. METHODS: We sampled female patients with an ICD-9/10 diagnosis of IC/BPS (595.1/N30.10) by querying active users of the Veterans Health Administration. Medical records were reviewed to determine whether patients met IC/BPS diagnostic criteria. A cohort of women with other pelvic pain disorders was identified. Prescription prevalence of typical non-narcotic oral bladder pain medications was compared between the two groups and healthy controls. Prescription prevalence was also compared before and after the diagnosis of IC/BPS was made using Poisson regression. RESULTS: There were 641 women who met criteria for IC/BPS and 197 women with "Other pelvic pain" disorders. Women with IC/BPS were prescribed a pain medication more often than those with "Other pelvic pain" (77% vs. 59%, p < 0.0001). Of the women with IC/BPS, 44% tried three or more pain medications. Of women with a diagnosis of IC/BPS, only 67% were prescribed an American Urological Association-recommended medication. Prescription prevalence increased after diagnosis for both pentosan polysulfate (10%-29%, p < 0.0001) and hydroxyzine (17%-40%, p < 0.0001), but not for amitriptyline or cimetidine. Amitriptyline was prescribed to 223 women with IC/BPS, only 125 of which (56%) had a documented history of depression. CONCLUSIONS: Many women with IC/BPS required multiple bladder prescriptions, highlighting the difficulty in finding an effective treatment for IC/BPS. Pentosan polysulfate and hydroxyzine were preferred IC/BPS medications. Our next step will be to analyze treatment patterns in those patients who did not receive medications.

    • Communicable Diseases
      1. Transactional sex, HIV and health among young cisgender men and transgender women who have sex with men in Thailandexternal icon
        Weir B, Dun C, Wirtz A, Mon S, Qaragholi N, Chemnasiri T, Pattanasin S, Wukwicha W, Varangrat A, Dunne. EF, Holtz T, Janyam S, Jin H, Linjongrat D, Mock P, Thigpen M, Rooney J, Sullivan P, Hickey A, Sirivongrangson P, Beyrer C, Poonkasetwattana M.
        Ann Epidemiol. 2022 Apr 8.
        PURPOSE: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex. METHODS: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n= 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "in the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated. RESULTS: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra®. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP. CONCLUSIONS: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population.

      2. A sub-group evaluation of the multi-month dispensing strategy for differentiated HIV care: is personalization of care guidelines warranted in Haiti?external icon
        Parrish C, Basu A, Fishman P, Koama JB, Robin E, Francois K, Honoré JG, Van Onacker JD, Puttkammer N.
        BMC Health Serv Res. 2022 Jan 16;22(1):80.
        BACKGROUND: Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. METHODS: This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. RESULTS: There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. CONCLUSIONS: All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines.

      3. Investigation of A SARS-CoV-2 Delta (B.1.617.2) variant outbreak among residents of a skilled nursing facility and vaccine effectiveness analysis - Maricopa County, Arizona, June-July 2021external icon
        Dale AP, Almendares O, Howard B, Burnett E, Prasai S, Arons M, Collins J, Duffy N, Pandit U, Brady S, White J, Garrett B, Kirking HL, Sunenshine R, Tate JE, Scott SE.
        Clin Infect Dis. 2022 Apr 12.
        BACKGROUND: Short-term rehabilitation units present unique infection control challenges due to high turnover and medically complex residents. In June 2021, Maricopa County Department of Public Health (MCDPH) was notified of a SARS-CoV-2 Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE). METHODS: Facility electronic medical records were reviewed for residents who spent >1 night on the affected unit between June 10-July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. COVID-19 VE estimates using Cox proportional hazards models were calculated. RESULTS: Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2 positive case-patients were mostly male (58%) and white (78%) with a median age of 65 (range: 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases; 32 non-cases) received 2-doses and 9% (4 cases, 6 non-cases) received 1-dose of mRNA vaccine. Among non-immunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% CI: 15, 95). More cases were hospitalized (33%) or died (38%) than non-cases (10% hospitalized; 16% died). CONCLUSIONS: In this large SARS-CoV-2 Delta outbreak in a high-turnover short term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in non-immunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks.

      4. Associations between mobility, food insecurity and transactional sex among women in cohabitating partnerships: an analysis from six African countries 2016-2017external icon
        Khalifa A, Findley S, Gummerson E, Mantell JE, Hakim AJ, Philip NM, Ginindza C, Hassani AS, Hong SY, Jalloh MF, Kirungi WL, Maile L, Mgomella GS, Miller LA, Minchella P, Mutenda N, Njau P, Schwitters A, Ward J, Low A.
        J Acquir Immune Defic Syndr. 2022 Apr 6.
        BACKGROUND: Mobile women are at risk of HIV infection in sub-Saharan Africa, though we lack evidence for HIV risk among women in mobile partnerships, especially in the context of household food insecurity, a growing concern in the region. SETTING: Women aged 15-59 years with a cohabitating male partner and who participated in Population-based HIV Impact Assessment surveys in Eswatini, Lesotho, Namibia, Tanzania, Uganda, and Zambia. METHODS: We evaluated the association between women's and their partner's mobility (being away from home for over one month or staying elsewhere) and transactional sex (selling sex or receiving money or goods in exchange for sex). We examined associations for effect measure modification by food insecurity level in the household in the past month. We used survey-weighted logistic regression, pooled and by country, adjusting for individual, partner and household-level variables. RESULTS: Among women with a cohabitating male partner, 8.0% reported transactional sex, ranging from 2.7% in Lesotho to 13.4% in Uganda. Women's mobility (aOR 1.35 [95% CI 1.08 - 1.68]), but not their partner's mobility (aOR 0.91 [0.74 - 1.12]), was associated with transactional sex. Food insecurity was associated with transactional sex independent of mobility (aOR 1.29 [1.10 - 1.52]). Among those who were food insecure, mobility was not associated with an increased odds of transactional sex. CONCLUSION: Food insecurity and women's mobility each increased the odds of transactional sex. Since transactional sex is associated with HIV risk, prevention programs can address the needs of mobile and food-insecure women, including those in cohabitating relationships.

      5. Comparable pregnancy outcomes for HIV-uninfected and HIV-infected women on antiretroviral treatment in Kenyaexternal icon
        Mugo C, Nduati R, Osoro E, Nyawanda BO, Mirieri H, Hunsperger E, Verani JR, Jin H, Mwaengo D, Maugo B, Machoki J, Otieno NA, Ombok C, Shabibi M, Okutoyi L, Kinuthia J, Widdowson MA, Njenga K, Inwani I, Wamalwa D.
        J Infect Dis. 2022 Apr 11.
        BACKGROUND: The impact of Human Immunodeficiency Virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear. METHODS: Pregnant women in Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with three pregnancy outcomes: loss, premature birth, and low birthweight and factors associated with HIV-positive status. RESULTS: Of 2,113 participants, 311 (15%) were HIV-infected and on ART. Ninety-one of 1,762 (5%) experienced a pregnancy loss, 169/1,725 (10%) a premature birth (<37 weeks), and 74/1,317 (6%) had a low birthweight newborn (<2500 g).There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk [aRR]: 1.19 [95% confidence interval: 0.65-2.16], p = 0.57), prematurity (1.09 [0.70-1.70], p = 0.69) and low birthweight (1.36 [0.77-2.40], p = 0.27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight. CONCLUSION: Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes.

      6. Invasive group A streptococcal disease in pregnant women and young children: a systematic review and meta-analysisexternal icon
        Sherwood E, Vergnano S, Kakuchi I, Bruce MG, Chaurasia S, David S, Dramowski A, Georges S, Guy R, Lamagni T, Levy-Bruhl D, Lyytikäinen O, Naus M, Okaro JO, Oppegaard O, Vestrheim DF, Zulz T, Steer AC, Van Beneden CA, Seale AC.
        Lancet Infect Dis. 2022 Apr 4.
        BACKGROUND: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years. METHODS: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I(2). FINDINGS: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I(2)=100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I(2)=100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I(2)=100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I(2)=100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I(2)=100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I(2)=100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I(2)=100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I(2)=100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I(2)=100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I(2)=100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I(2)=54%; two studies). INTERPRETATION: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS. FUNDING: Wellcome Trust.

      7. Notes from the field: Enteropathogenic escherichia coli outbreak at a child care center - Oregon, August 2021external icon
        Bonner KE, Carter M, Zielinski C, Morey K, McLitus L, DeBess E, Hatch J, Leman R.
        MMWR Morb Mortal Wkly Rep. 2022 Apr 8;71(14):527.

      8. Notes from the Field: SARS-CoV-2 Omicron variant infection in 10 persons within 90 days of previous SARS-CoV-2 Delta Variant infection - four states, October 2021-January 2022external icon
        Roskosky M, Borah BF, DeJonge PM, Donovan CV, Blevins LZ, Lafferty AG, Pringle JC, Kelso P, Temte JL, Temte E, Barlow S, Goss M, Uzicanin A, Bateman A, Florek K, Kawakami V, Lewis J, Loughran J, Pogosjans S, Kay M, Duchin J, Lunn S, Schnitzler H, Arora S, Tate J, Ricaldi J, Kirking H.
        MMWR Morb Mortal Wkly Rep. 2022 Apr 8;71(14):524-526.

      9. Annual STI testing among sexually active adolescentsexternal icon
        Liddon N, Pampati S, Dunville R, Kilmer G, Steiner RJ.
        Pediatrics. 2022 Apr 11.
        OBJECTIVES: National guidelines call for annual testing for certain sexually transmitted infections (STIs) among specific adolescent populations, yet we have limited population-based data on STI testing prevalence among adolescents. With inclusion of a new item in the 2019 national Youth Risk Behavior Survey, we provide generalizable estimates of annual STI testing among sexually active high school students. METHODS: We report weighted prevalence estimates of STI testing (other than HIV) in the past 12 months among sexually active students (n = 2501) and bivariate associations between testing and demographic characteristics (sex, age, race and ethnicity, sexual identity, and sex of sexual contact). Multivariable models stratified by sex and adjusted for demographics examine the relationships between testing and sexual behaviors (age of initiation, number of sex partners, condom nonuse at last sexual intercourse, and substance use at last sexual intercourse). RESULTS: One-fifth (20.4%) of sexually active high school students reported testing for an STI in the previous year. A significantly higher proportion of female (26.1%) than male (13.7%) students reported testing. Among female students, prevalence differed by age (≤15 years = 12.6%, age 16 = 22.8%, age 17 = 28.5%, or ≥18 years = 36.9%). For male students, there were no differences by demographic characteristics, including sexual identity, but most sexual risk behaviors were associated with increased likelihood of STI testing (adjusted prevalence ratios ranging from 1.48 to 2.47). CONCLUSIONS: Low prevalence of STI testing suggests suboptimal adherence to national guidelines, particularly for sexually active adolescent females and young men who have sex with men who should be tested for Chlamydia and gonorrhea annually.

    • Community Health Services
      1. Minnesota refugees diagnosed with tuberculosis disease, January 1993-August 2019external icon
        Urban K, Mamo B, Thai D, Earnest A, Jentes E.
        BMC Infect Dis. 2022 Apr 9;22(1):356.
        BACKGROUND: Refugees are screened for TB overseas using Technical Instructions (TIs) issued by the U.S. Centers for Disease Control and Prevention and after arrival during their refugee health assessment (RHA). We examined RHA results and TB outcomes of refugees to Minnesota. METHODS: Demographic and RHA results for 70,290 refugee arrivals to Minnesota from January 1993 to August 2019 were matched to 3595 non-U.S. born individuals diagnosed with TB disease during that time. RESULTS: Seven hundred fifty-nine (1.1%) were diagnosed with TB disease. Fifty-four percent were diagnosed within 2 years of U.S. arrival. Refugees screened using TIs implemented in 1991 were twice as likely to be diagnosed with TB disease within 1 year of arrival, compared to those evaluated using improved TIs implemented in 2007. CONCLUSION: Few refugees were diagnosed with TB disease during the period examined. Enhancements to overseas protocols significantly reduced the proportion of refugees diagnosed within 1 year of arrival.

      2. Clinic- and community-based SARS-CoV-2 testing among people experiencing homelessness in the United States, March-November 2020external icon
        Berner L, Meehan A, Kenkel J, Montgomery M, Fields V, Henry A, Boyer A, Mosites E, Vickery KD.
        Public Health Rep. 2022 Apr 9:333549221086514.
        OBJECTIVE: SARS-CoV-2 testing is a critical component of preventing the spread of COVID-19. In the United States, people experiencing homelessness (PEH) have accessed testing at health clinics, such as those provided through Health Care for the Homeless (HCH) clinics or through community-based testing events at homeless service sites or encampments. We describe data on SARS-CoV-2 testing among PEH in US clinic- and community-based settings from March through November 2020. METHODS: We conducted a descriptive analysis of data from HCH clinics and community testing events. We used a standardized survey to request data from HCH clinics. We developed and made publicly available an online data entry portal to collect data from community-based organizations that provided testing for PEH. We assessed positivity rates across clinics and community service sites serving PEH and used generalized linear mixed models to account for clustering. RESULTS: Thirty-seven HCH clinics reported providing 280 410 tests; 3.2% (n = 8880) had positive results (range, 1.6%-4.9%). By race, positivity rates were highest among people who identified as >1 race (11.6%; P < .001). During the reporting period, 22 states reported 287 community testing events and 14 116 tests; 7.1% (n = 1004) had positive results. Among facility types, day shelters (380 of 2697; 14.1%) and inpatient drug/alcohol rehabilitation facilities (32 of 251; 12.7%) reported the highest positivity rates. CONCLUSIONS: While HCH clinic data provided results for a larger number of patients, community-based testing data showed higher positivity rates. Clinic data demonstrated racial disparities in positivity. Community-based testing data provided information about SARS-CoV-2 transmission settings. Although these data provide information about testing, standard surveillance systems are needed to better understand the incidence of disease among PEH.

    • Disaster Preparedness and Emergency Services
      1. Winter storms and unplanned school closure announcements on Twitter: Comparison between the states of Massachusetts and Georgia, 2017-2018external icon
        Evans HI, Handberry MT, Muniz-Rodriguez K, Schwind JS, Liang H, Adhikari BB, Meltzer MI, Fung IC.
        Disaster Med Public Health Prep. 2022 Apr 11:1-9.
        OBJECTIVE: This project aimed to quantify and compare Massachusetts and Georgia public school districts' 2017-2018 winter-storm-related Twitter unplanned school closure announcements (USCA). METHODS: Public school district Twitter handles and National Center for Education Statistics data were obtained for Georgia and Massachusetts. Tweets were retrieved using Twitter application programming interface. Descriptive statistics and regression analyses were conducted to compare the rates of winter-storm-related USCA. RESULTS: Massachusetts had more winter storms than Georgia during the 2017-2018 winter season, but Massachusetts school districts posted winter-storm-related USCA at a 60% lower rate per affected day (adjusted rate ratio, aRR = 0.40, 95% confidence intervals, CI: 0.30, 0.52) than Georgia school districts after controlling for the student enrollments and Twitter followers count per Twitter account. A 10-fold increase in followers count was correlated with a 118% increase in USCA rate per affected day (aRR = 2.18; 95% CI: 1.74, 2.75). Georgia school districts had a higher average USCA tweet rate per winter-storm-affected day than Massachusetts school districts. A higher number of Twitter followers was associated with a higher number of USCA tweets per winter-storm-affected day. CONCLUSION: Twitter accounts of school districts in Massachusetts had a lower tweet rate for USCA per winter-storm-affected days than those in Georgia.

    • Disease Reservoirs and Vectors
      1. Molecular characterization of rickettsial agents in ticks (Acari: Ixodidae) from Sri Lankaexternal icon
        Dasch GA, Eremeeva ME, Zambrano ML, Premaratna R, Kularatne SA, Jayanthe Rajapakse RP.
        Am J Trop Med Hyg. 2022 Apr 11.
        Because the majority of spotted fever group rickettsiae are transmitted to humans by tick bites, it is important to understand which ticks might play a role in transmission of rickettsial pathogens in Sri Lanka. The purpose of our study was to conduct molecular surveillance of 847 ticks collected in different locations in central Sri Lanka to determine which were infected with Rickettsia and Anaplasmataceae. Molecular methods were used to identify the ticks and the agents detected. Most ticks (Amblyomma, Haemaphysalis, and Rhipicephalus) were collected by flagging, and lower number was collected from dogs, cattle, pigs, a pangolin, and tortoises. Five spotted fever genotypes were identified: a Rickettsia africae-like agent in Amblyomma larvae, Rhipicephalus massiliae and a related genotype identified in association with the tropical type of Rhipicephalus sanguineus from dogs and Rhipicephalus haemaphysaloides from dogs and cattle, and Candidatus R. kellyi and another novel genotype (SL94) in R. haemaphysaloides. Twenty-three ticks were positive for Anaplasmataceae, including one Anaplasma and two Ehrlichia genotypes. Because the sequence database for both ticks and rickettsial agents from Sri Lanka and southern India is not extensive, additional molecular characterization of the tick species of Sri Lanka and their rickettsial agents is required to understand their pathogenic potential more completely. However, several of the agents we identified in this survey may well be pathogenic for humans and domestic animals, and should be considered as a part of epidemiological surveillance and patient management.

      2. Fitness cost of sequential selection with deltamethrin in Aedes aegypti (Diptera: Culicidae)external icon
        Gonzalez-Santillan FJ, Contreras-Perera Y, Davila-Barboza JA, Juache-Villagrana AE, Gutierrez-Rodriguez SM, Ponce-Garcia G, Lopez-Monroy B, Rodriguez-Sanchez IP, Lenhart AE, Mackenzie-Impoinvil L, Flores AE.
        J Med Entomol. 2022 Apr 7.
        In Mexico, Aedes aegypti (L.) is the primary dengue vector, chikungunya, and Zika viruses. The continued use of synthetic pyrethroids has led to the development of resistance in target populations, which has diminished the effectiveness of vector control programs. Resistance has been associated with disadvantages that affect the biological parameters of resistant mosquitoes compared to susceptible ones. In the present study, the disadvantages were evaluated by parameters related to survival and reproduction ('fitness cost') after selection with deltamethrin for five generations. The parameters analyzed were the length of the development cycle, sex ratio, survival, longevity, fecundity, egg viability, preoviposition, oviposition and postoviposition periods, and growth parameters. In the deltamethrin-selected strain, there was a decrease in the development cycle duration, the percentage of pupae, the oviposition period, and eggs viability. Although mean daily fecundity was not affected after the selection process, this, together with the decrease in the survival and fecundity levels by specific age, significantly affected the gross reproductive rate (GRR), net reproductive rate (Ro), and intrinsic growth rate (rm) of the group selected for five generations with deltamethrin compared to the group without selection. Identifying the 'cost' of resistance in biological fitness represents an advantage if it is desired to limit the spread of resistant populations since the fitness cost is the less likely that resistant individuals will spread in the population. This represents an important factor to consider in designing integrated vector management programs.

    • Drug Safety
      1. Prescription history among individuals dispensed opioid prescriptions, 2017-2020external icon
        Strahan AE, Nataraj N, Guy GP, Losby JL, Dowell D.
        Am J Prev Med. 2022 Apr 5.

    • Environmental Health
      1. Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the Study of Women's Health Across the Nation (SWAN)external icon
        Park SK, Wang X, Ding N, Karvonen-Gutierrez CA, Calafat AM, Herman WH, Mukherjee B, Harlow SD.
        Diabetologia. 2022 Apr 11.
        AIMS/HYPOTHESIS: Diabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS). METHODS: We included 1237 diabetes-free women aged 45-56 years at baseline (1999-2000) who were followed up to 2017. At each follow-up visit, women with incident diabetes were identified by the presence of one or more of the following conditions: (1) use of a glucose-lowering medication at any visit; (2) fasting glucose ≥7 mmol/l on two consecutive visits while not on steroids; and (3) any two visits with self-reported diabetes and at least one visit with fasting blood glucose ≥7 mmol/l. Serum concentrations of 11 PFAS were quantified by online solid-phase extraction-HPLC-isotope dilution-tandem MS. Seven PFAS with high detection rates (>96%) (n-perfluorooctanoic acid [n-PFOA], perfluorononanoic acid [PFNA], perfluorohexane sulfonic acid [PFHxS], n-perfluorooctane sulfonic acid [n-PFOS], sum of perfluoromethylheptane sulfonic acid isomers [Sm-PFOS], 2-[N-methyl-perfluorooctane sulfonamido] acetic acid [MeFOSAA] and 2-[N-ethyl-perfluorooctane sulfonamido] acetic acid) were included in data analysis. Cox proportional hazards models were used to compute HRs and 95% CIs. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: After adjustment for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI, the HR (95% CI) comparing the lowest with the highest tertile was 1.67 (1.21, 2.31) for n-PFOA (p(trend) = 0.001), 1.58 (1.13, 2.21) for PFHxS (p(trend) = 0.003), 1.36 (0.97, 1.90) for Sm-PFOS (p(trend) = 0.05), 1.85 (1.28, 2.67) for MeFOSAA (p(trend) = 0.0004) and 1.64 (1.17, 2.31) for the sum of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) (p(trend) = 0.002). Exposure to seven PFAS as mixtures was associated with an HR of 2.62 (95% CI 1.12, 6.20), comparing the top with the bottom tertiles for all seven PFAS. CONCLUSIONS/INTERPRETATION: This study suggests that PFAS may increase diabetes risk in midlife women. Reduced exposure to these 'forever and everywhere chemicals' may be an important preventative approach to lowering population-wide diabetes risk.

      2. Evaluating predictive relationships between wristbands and urine for assessment of personal PAH exposureexternal icon
        Dixon HM, Bramer LM, Scott RP, Calero L, Holmes D, Gibson EA, Cavalier HM, Rohlman D, Miller RL, Calafat AM, Kincl L, Waters KM, Herbstman JB, Anderson KA.
        Environ Int. 2022 Apr 4;163:107226.
        During events like the COVID-19 pandemic or a disaster, researchers may need to switch from collecting biological samples to personal exposure samplers that are easy and safe to transport and wear, such as silicone wristbands. Previous studies have demonstrated significant correlations between urine biomarker concentrations and chemical levels in wristbands. We build upon those studies and use a novel combination of descriptive statistics and supervised statistical learning to evaluate the relationship between polycyclic aromatic hydrocarbon (PAH) concentrations in silicone wristbands and hydroxy-PAH (OH-PAH) concentrations in urine. In New York City, 109 participants in a longitudinal birth cohort wore one wristband for 48 h and provided a spot urine sample at the end of the 48-hour period during their third trimester of pregnancy. We compared four PAHs with the corresponding seven OH-PAHs using descriptive statistics, a linear regression model, and a linear discriminant analysis model. Five of the seven PAH and OH-PAH pairs had significant correlations (Pearson's r = 0.35-0.64, p ≤ 0.003) and significant chi-square tests of independence for exposure categories (p ≤ 0.009). For these five comparisons, the observed PAH or OH-PAH concentration could predict the other concentration within a factor of 1.47 for 50-80% of the measurements (depending on the pair). Prediction accuracies for high exposure categories were at least 1.5 times higher compared to accuracies based on random chance. These results demonstrate that wristbands and urine provide similar PAH exposure assessment information, which is critical for environmental health researchers looking for the flexibility to switch between biological sample and wristband collection.

      3. Age effects on radiation response: summary of a recent symposium and future perspectivesexternal icon
        Little MP, Brenner AV, Grant EJ, Sugiyama H, Preston DL, Sakata R, Cologne J, Velazquez-Kronen R, Utada M, Mabuchi K, Ozasa K, Olson JD, Dugan GO, Pazzaglia S, Cline JM, Applegate KE.
        Int J Radiat Biol. 2022 Apr 8:1-34.

      4. Asbestos fiber length and width comparison between manual and semi-automated measurementsexternal icon
        Lee T, Barone T, Rubinstein E, Mischler S.
        J Occup Environ Hyg. 2022 Apr 8:1-12.
        The objective of the present study is to find a fast and accurate procedure to measure the length and width of asbestos fibers using images acquired by a scanning electron microscope (SEM), a phase contrast microscope (PCM), and a polarized light microscope (PLM). The accuracy of the procedure was evaluated by comparing fiber length and width measurements to manual measurements. Four different types of images were used in the evaluation: 1) backscattered electron SEM images of fibrous tremolite, 2) secondary electron SEM images of fibrous grunerite, 3) PCM images of fibrous grunerite, and 4) PLM images of fibrous grunerite. Fiber length and width were measured with ImageJ (manual measurement) and Image-Pro software and were compared on an individual fiber basis and over the number-length and number-width distribution of each sample. The results of the comparison showed that the individual length and width measurements with ImageJ and Image-Pro software had a nearly 1:1 relationship except for the width measurement in PLM images (8% of the variance in ImageJ width measurements was not explained by Image-Pro width measurements). Similarly, the number-length distributions were not significantly different (p > 0.05) between ImageJ and Image-Pro, but the number-width distributions were significantly different (p < 0.05) for PLM and secondary electron SEM images. Although the image analysis procedure for measuring fiber length and width with Image-Pro is not a fully automated procedure and still requires some manual intervention, it can be a more efficient and equally accurate alternative to time-consuming manual fiber length and width measurements for well dispersed fibers with high aspect ratios.

    • Epidemiology and Surveillance
      1. Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United Statesexternal icon
        Cramer EY, Ray EL, Lopez VK, Bracher J, Brennen A, Castro Rivadeneira AJ, Gerding A, Gneiting T, House KH, Huang Y, Jayawardena D, Kanji AH, Khandelwal A, Le K, Mühlemann A, Niemi J, Shah A, Stark A, Wang Y, Wattanachit N, Zorn MW, Gu Y, Jain S, Bannur N, Deva A, Kulkarni M, Merugu S, Raval A, Shingi S, Tiwari A, White J, Abernethy NF, Woody S, Dahan M, Fox S, Gaither K, Lachmann M, Meyers LA, Scott JG, Tec M, Srivastava A, George GE, Cegan JC, Dettwiller ID, England WP, Farthing MW, Hunter RH, Lafferty B, Linkov I, Mayo ML, Parno MD, Rowland MA, Trump BD, Zhang-James Y, Chen S, Faraone SV, Hess J, Morley CP, Salekin A, Wang D, Corsetti SM, Baer TM, Eisenberg MC, Falb K, Huang Y, Martin ET, McCauley E, Myers RL, Schwarz T, Sheldon D, Gibson GC, Yu R, Gao L, Ma Y, Wu D, Yan X, Jin X, Wang YX, Chen Y, Guo L, Zhao Y, Gu Q, Chen J, Wang L, Xu P, Zhang W, Zou D, Biegel H, Lega J, McConnell S, Nagraj VP, Guertin SL, Hulme-Lowe C, Turner SD, Shi Y, Ban X, Walraven R, Hong QJ, Kong S, van de Walle A, Turtle JA, Ben-Nun M, Riley S, Riley P, Koyluoglu U, DesRoches D, Forli P, Hamory B, Kyriakides C, Leis H, Milliken J, Moloney M, Morgan J, Nirgudkar N, Ozcan G, Piwonka N, Ravi M, Schrader C, Shakhnovich E, Siegel D, Spatz R, Stiefeling C, Wilkinson B, Wong A, Cavany S, España G, Moore S, Oidtman R, Perkins A, Kraus D, Kraus A, Gao Z, Bian J, Cao W, Lavista Ferres J, Li C, Liu TY, Xie X, Zhang S, Zheng S, Vespignani A, Chinazzi M, Davis JT, Mu K, Pastore YP, Xiong X, Zheng A, Baek J, Farias V, Georgescu A, Levi R, Sinha D, Wilde J, Perakis G, Bennouna MA, Nze-Ndong D, Singhvi D, Spantidakis I, Thayaparan L, Tsiourvas A, Sarker A, Jadbabaie A, Shah D, Della Penna N, Celi LA, Sundar S, Wolfinger R, Osthus D, Castro L, Fairchild G, Michaud I, Karlen D, Kinsey M, Mullany LC, Rainwater-Lovett K, Shin L, Tallaksen K, Wilson S, Lee EC, Dent J, Grantz KH, Hill AL, Kaminsky J, Kaminsky K, Keegan LT, Lauer SA, Lemaitre JC, Lessler J, Meredith HR, Perez-Saez J, Shah S, Smith CP, Truelove SA, Wills J, Marshall M, Gardner L, Nixon K, Burant JC, Wang L, Gao L, Gu Z, Kim M, Li X, Wang G, Wang Y, Yu S, Reiner RC, Barber R, Gakidou E, Hay SI, Lim S, Murray C, Pigott D, Gurung HL, Baccam P, Stage SA, Suchoski BT, Prakash BA, Adhikari B, Cui J, Rodríguez A, Tabassum A, Xie J, Keskinocak P, Asplund J, Baxter A, Oruc BE, Serban N, Arik SO, Dusenberry M, Epshteyn A, Kanal E, Le LT, Li CL, Pfister T, Sava D, Sinha R, Tsai T, Yoder N, Yoon J, Zhang L, Abbott S, Bosse NI, Funk S, Hellewell J, Meakin SR, Sherratt K, Zhou M, Kalantari R, Yamana TK, Pei S, Shaman J, Li ML, Bertsimas D, Skali Lami O, Soni S, Tazi Bouardi H, Ayer T, Adee M, Chhatwal J, Dalgic OO, Ladd MA, Linas BP, Mueller P, Xiao J, Wang Y, Wang Q, Xie S, Zeng D, Green A, Bien J, Brooks L, Hu AJ, Jahja M, McDonald D, Narasimhan B, Politsch C, Rajanala S, Rumack A, Simon N, Tibshirani RJ, Tibshirani R, Ventura V, Wasserman L, O'Dea EB, Drake JM, Pagano R, Tran QT, Ho LS, Huynh H, Walker JW, Slayton RB, Johansson MA, Biggerstaff M, Reich NG.
        Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2113561119.
        SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.

    • Food Safety
      1. Litter commensal bacteria can limit the horizontal gene transfer of antimicrobial resistance to Salmonella in chickensexternal icon
        Oladeinde A, Abdo Z, Zwirzitz B, Woyda R, Lakin SM, Press MO, Cox NA, Thomas JC, Looft T, Rothrock MJ, Zock G, Plumblee Lawrence J, Cudnik D, Ritz C, Aggrey SE, Liachko I, Grove JR, Wiersma C.
        Appl Environ Microbiol. 2022 Apr 13:e0251721.
        Fostering a "balanced" gut microbiome through the administration of beneficial microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known about how microbes affect the horizontal gene transfer of antimicrobial resistance (AMR). To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter-a complex environment made up of decomposing pine shavings, feces, uric acid, feathers, and feed-with Salmonella enterica serovar Heidelberg (S. Heidelberg), a model pathogen. Neonatal chicks challenged with S. Heidelberg and raised on reused litter were more resistant to S. Heidelberg cecal colonization than chicks grown on fresh litter. Furthermore, chicks grown on reused litter were at a lower risk of colonization with S. Heidelberg strains that encoded AMR on IncI1 plasmids. We used 16S rRNA gene sequencing and shotgun metagenomics to show that the major difference between chicks grown on fresh litter and those grown on reused litter was the microbiome harbored in the litter and ceca. The microbiome of reused litter samples was more uniform and enriched in functional pathways related to the biosynthesis of organic and antimicrobial molecules than that in fresh litter samples. We found that Escherichia coli was the main reservoir of plasmids encoding AMR and that the IncI1 plasmid was maintained at a significantly lower copy per cell in reused litter compared to fresh litter. These findings support the notion that commensal bacteria play an integral role in the horizontal transfer of plasmids encoding AMR to pathogens like Salmonella. IMPORTANCE Antimicrobial resistance spread is a worldwide health challenge, stemming in large part from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organizations have adopted a One Health approach to curtail the proliferation of antimicrobial-resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we show that commensal bacteria play a key role in reducing the horizontal gene transfer of antibiotic resistance to Salmonella, provide the identity of the bacterial species that potentially perform this function in broiler chickens, and also postulate the mechanism involved.

    • Genetics and Genomics
      1. Phylogenetic structure and comparative genomics of multi-national invasive haemophilus influenzae serotype a isolatesexternal icon
        Topaz N, Tsang R, Deghmane AE, Claus H, Lâm TT, Litt D, Bajanca-Lavado MP, Pérez-Vázquez M, Vestrheim D, Giufrè M, Van Der Ende A, Gaillot O, Kuch A, McElligott M, Taha MK, Wang X.
        Front Microbiol. 2022 ;13:856884.
        Recent reports have indicated a rise of invasive disease caused by Haemophilus influenzae serotype a (Hia) in North America and some European countries. The whole-genome sequences for a total of 410 invasive Hia isolates were obtained from 12 countries spanning the years of 1998 to 2019 and underwent phylogenetic and comparative genomic analysis in order to characterize the major strains causing disease and the genetic variation present among factors contributing to virulence and antimicrobial resistance. Among 410 isolate sequences received, 408 passed our quality control and underwent genomic analysis. Phylogenetic analysis revealed that the Hia isolates formed four genetically distinct clades: clade 1 (n = 336), clade 2 (n = 13), clade 3 (n = 3) and clade 4 (n = 56). A low diversity subclade 1.1 was found in clade 1 and contained almost exclusively North American isolates. The predominant sequence types in the Hia collection were ST-56 (n = 125), ST-23 (n = 98) and ST-576 (n = 51), which belonged to clade 1, and ST-62 (n = 54), which belonged to clade 4. Clades 1 and 4 contained predominantly North American isolates, and clades 2 and 3 predominantly contained European isolates. Evidence of the presence of capsule duplication was detected in clade 1 and 2 isolates. Seven of the virulence genes involved in endotoxin biosynthesis were absent from all Hia isolates. In general, the presence of known factors contributing to β-lactam antibiotic resistance was low among Hia isolates. Further tests for virulence and antibiotic susceptibility would be required to determine the impact of these variations among the isolates.

      2. Burkholderia pseudomallei causes melioidosis. Sequence typing this pathogen can reveal geographical origin and uncover epidemiological associations. Here, we describe B. pseudomallei genes encoding putative penicillin binding proteins (PBPs) and investigate their utility for determining phylogeography and differentiating closely related species. We performed in silico analysis to characterize 10 PBP homologs in B. pseudomallei 1026b. As PBP active site mutations can confer β-lactam resistance in Gram-negative bacteria, PBP sequences in two resistant B. pseudomallei strains were examined for similar alterations. Sequence alignments revealed single amino acid polymorphisms (SAAPs) unique to the multidrug resistant strain Bp1651 in the transpeptidase domains of two PBPs, but not directly within the active sites. Using BLASTn analyses of complete assembled genomes in the NCBI database, we determined genes encoding PBPs were conserved among B. pseudomallei (n = 101) and Burkholderia mallei (n = 26) strains. Within these genes, single nucleotide polymorphisms (SNPs) useful for predicting geographic origin of B. pseudomallei were uncovered. SNPs unique to B. mallei were also identified. Based on 11 SNPs identified in two genes encoding predicted PBP-3s, a dual-locus sequence typing (DLST) scheme was developed. The robustness of this typing scheme was assessed using 1,523 RefSeq genomes from B. pseudomallei (n = 1,442) and B. mallei (n = 81) strains, resulting in 32 sequence types (STs). Compared to multi-locus sequence typing (MLST), the DLST scheme demonstrated less resolution to support the continental separation of Australian B. pseudomallei strains. However, several STs were unique to strains originating from a specific country or region. The phylogeography of Western Hemisphere B. pseudomallei strains was more highly resolved by DLST compared to internal transcribed spacer (ITS) typing, and all B. mallei strains formed a single ST. Conserved genes encoding PBPs in B. pseudomallei are useful for strain typing, can enhance predictions of geographic origin, and differentiate strains of closely related Burkholderia species.

    • Global Health
      1. Fourteen mcr-1-positive Salmonella enterica isolates recovered from travelers returning to the United States from the Dominican Republicexternal icon
        Webb HE, Kim JY, Tagg KA, Kapsak CJ, Tobolowsky F, Birhane MG, Francois Watkins L, Folster JP.
        Microbiol Resour Announc. 2022 Apr 13:e0011822.
        In the United States, reports of Salmonella enterica carrying mcr-1 remain rare in humans, but when observed, the infection is often associated with travel. Here, we report 14 mcr-1-positive Salmonella enterica isolates from patients in the United States that reported travel to the Dominican Republic within the 12 months before illness.

      2. Monkeypox in a traveler returning from Nigeria - Dallas, Texas, July 2021external icon
        Rao AK, Schulte J, Chen TH, Hughes CM, Davidson W, Neff JM, Markarian M, Delea KC, Wada S, Liddell A, Alexander S, Sunshine B, Huang P, Honza HT, Rey A, Monroe B, Doty J, Christensen B, Delaney L, Massey J, Waltenburg M, Schrodt CA, Kuhar D, Satheshkumar PS, Kondas A, Li Y, Wilkins K, Sage KM, Yu Y, Yu P, Feldpausch A, McQuiston J, Damon IK, McCollum AM.
        MMWR Morb Mortal Wkly Rep. 2022 Apr 8;71(14):509-516.
        Monkeypox is a rare, sometimes life-threatening zoonotic infection that occurs in west and central Africa. It is caused by Monkeypox virus, an orthopoxvirus similar to Variola virus (the causative agent of smallpox) and Vaccinia virus (the live virus component of orthopoxvirus vaccines) and can spread to humans. After 39 years without detection of human disease in Nigeria, an outbreak involving 118 confirmed cases was identified during 2017-2018 (1); sporadic cases continue to occur. During September 2018-May 2021, six unrelated persons traveling from Nigeria received diagnoses of monkeypox in non-African countries: four in the United Kingdom and one each in Israel and Singapore. In July 2021, a man who traveled from Lagos, Nigeria, to Dallas, Texas, became the seventh traveler to a non-African country with diagnosed monkeypox. Among 194 monitored contacts, 144 (74%) were flight contacts. The patient received tecovirimat, an antiviral for treatment of orthopoxvirus infections, and his home required large-scale decontamination. Whole genome sequencing showed that the virus was consistent with a strain of Monkeypox virus known to circulate in Nigeria, but the specific source of the patient's infection was not identified. No epidemiologically linked cases were reported in Nigeria; no contact received postexposure prophylaxis (PEP) with the orthopoxvirus vaccine ACAM2000.

    • Health Communication and Education
      1. COVID-19 vaccine inquiries regarding children ages 5-11 years received by NIP-INFOexternal icon
        Hall E, Morales S, Wolicki J, Schillie S.
        Public Health Nurs. 2022 Apr 12.
        We describe COVID-19 immunization inquiries regarding children age 5-11 years received by NIP-INFO, the Centers for Disease Control and Prevention's (CDC's) e-mail immunization inquiry service for health care professionals, at the launch of vaccination efforts for this age group, using descriptive qualitative analysis. From November 2 through November 30, 2021, NIP-INFO responded to 154 questions regarding COVID-19 vaccination for 5-11-year-old children. The most common questions related to formulation and dosage (39.6%), vaccination schedule (14.3%), CDC's educational materials for health care professionals (9.1%), and vaccine safety (8.4%); 16.2% of questions across all inquiry categories related to a vaccination error. We discuss CDC guidance related to the most common inquiries to inform further pediatric COVID-19 vaccination efforts, including future vaccination of younger pediatric age groups, which will be important to help to curb this pandemic.

    • Health Equity and Health Disparities
      1. Disparities in COVID-19 mortality rates: Implications for rural health policy and preparednessexternal icon
        Grome HN, Raman R, Katz BD, Fill MM, Jones TF, Schaffner W, Dunn J.
        J Public Health Manag Pract. 2022 Apr 5.
        CONTEXT: It is well established that rural communities face geographic and socioeconomic challenges linked to higher rates of health disparities across the United States, though the coronavirus disease 2019 (COVID-19) impact on rural communities is less certain. OBJECTIVE: To understand the COVID-19 pandemic's impact on rural communities in Tennessee, investigate differences in rural-urban mortality rates after controlling for confounding variables, and inform state pandemic response policy. DESIGN: A cross-sectional analysis of cumulative COVID-19 morality rates. SETTING/PARTICIPANTS: Tennessee county-level COVID-19 mortality data from March 1, 2020, to January 31, 2021, were matched with county-level sociodemographic and health data from public datasets: Agency for Healthcare Research and Quality Social Determinants of Health, PLACES: Local Data for Better Health County Data, and the US Census Bureau. County status was defined using the 2013 National Center for Health Statistics Urban-Rural Classification. MAIN OUTCOME MEASURES: A negative binomial regression model estimated adjusted incidence rate ratio and 95% confidence intervals (CI) for rural compared with urban mortality. Unadjusted rate ratios and rate differences for COVID-19 mortality in rural versus urban counties were compared with those for influenza and pneumonia and all-cause mortality over the past 5 years. RESULTS: During the study period, 9650 COVID-19 deaths occurred across 42 urban and 53 rural counties. Controlling for county-level sociodemographic characteristics, health care access, and comorbidities, incidence rate ratio was 1.13 (95% CI, 1.00-1.28, P < .05) for rural as compared with urban deaths. Unadjusted COVID-19 mortality risk difference between rural and urban counties was greater (61.85, 95% CI, 54.31-69.31) than 5-year influenza and pneumonia rural-urban risk difference (12.57, 95% CI, 11.16-13.00) during 2015-2019. CONCLUSIONS: COVID-19 mortality rates were greater for populations living in Tennessee's rural as compared with urban counties during the study period. This differential impact must be considered in public health decision making to mitigate COVID-19.

      2. Changes and inequities in adult mental health-related emergency department visits during the COVID-19 pandemic in the USexternal icon
        Anderson KN, Radhakrishnan L, Lane RI, Sheppard M, DeVies J, Azondekon R, Smith AR, Bitsko RH, Hartnett KP, Lopes-Cardozo B, Leeb RT, van Santen KL, Carey K, Crossen S, Dias TP, Wotiz S, Adjemian J, Rodgers L, Njai R, Thomas C.
        JAMA Psychiatry. 2022 Mar 16.
        IMPORTANCE: The COVID-19 pandemic has negatively affected adult mental health (MH), with racial and ethnic minoritized groups disproportionately affected. OBJECTIVE: To examine changes in adult MH-related emergency department (ED) visits into the Delta variant pandemic period and identify changes and inequities in these visits before and during COVID-19 case surges. DESIGN, SETTING, AND PARTICIPANTS: This epidemiologic cross-sectional study used National Syndromic Surveillance Program data from US adults aged 18 to 64 years from 1970 to 2352 ED facilities from January 1, 2019, to August 14, 2021. All MH-related ED visits and visits related to 10 disorders (ie, anxiety, depressive, bipolar, schizophrenia spectrum, trauma- and stressor-related, attention-deficit/hyperactivity, disruptive behavioral and impulse, obsessive-compulsive, eating, and tic disorders) were identified. EXPOSURES: The following periods of MH-related ED visits were compared: (1) high Delta variant circulation (July 18-August 14, 2021) with a pre-Delta period (April 18-May 15, 2021), (2) after a COVID-19 case peak (February 14-March 13, 2021) with during a peak (December 27, 2020-January 23, 2021), and (3) the Delta period and the period after a COVID-19 case peak with the respective corresponding weeks during the prepandemic period. MAIN OUTCOMES AND MEASURES: ED visits for 10 mental disorders and all MH-related visits. RESULTS: This cross-sectional study included 107 761 319 ED visits among adults aged 18 to 64 years (59 870 475 [56%] women) from January 1, 2019, to August 14, 2021. There was stability in most MH-related ED visit counts between the Delta and pre-Delta periods (percentage change, -1.4% to -7.5%), except for eating disorders (-11.9%) and tic disorders (-19.8%) and after a COVID-19 case peak compared with during a peak (0.6%-7.4%). Most MH-related ED visit counts declined in the Delta period relative to the prepandemic period (-6.4% to -30.7%); there were fluctuations by disorder when comparing after a COVID-19 case peak with the corresponding prepandemic period (-15.4% to 11.3%). Accounting for ED visit volume, MH-related ED visits were a smaller proportion of visits in the Delta period compared with the pre-Delta period (visit ratio, 0.86; 95% CI, 0.85-0.86) and prepandemic period (visit ratio, 0.80; 95% CI, 0.79-0.80). After a COVID-19 case peak, MH-related ED visits were a larger proportion of ED visits compared with during a peak (visit ratio, 1.04; 95% CI, 1.03-1.04) and the corresponding prepandemic period (visit ratio, 1.11; 95% CI, 1.11-1.12). Of the 2 510 744 ED visits included in the race and ethnicity analysis, 24 592 (1%) were American Indian or Alaska Native persons, 33 697 (1%) were Asian persons, 494 198 (20%) were Black persons, 389 740 (16%) were Hispanic persons, 5000 (0.2%) were Native Hawaiian or Other Pacific Islander persons, and 1 172 683 (47%) were White persons. There was between- and within-group variation in ED visits by race and ethnicity and increases in selected disorders after COVID-19 peaks for adults aged 18 to 24 years. CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that EDs may have increases in MH-related visits after COVID-19 surges, specifically for young adults and individual racial and ethnic minoritized subpopulations. Public health practitioners should consider subpopulation-specific messaging and programmatic strategies that address differences in MH needs, particularly for those historically marginalized.

      3. Language barriers have been associated with worse access to healthcare and poorer health outcomes. To assess differences in access to care and utilization of healthcare services between Hispanic adults and non-Hispanic white adults (NHW), we used the Medical Expenditure Panel Survey (2013-2016) to compare Hispanic adults who expressed limited comfort speaking in English (LCE) with Hispanic adults who were comfortable speaking in English (CE) and NHW adults. Hispanic adults with CE were less likely than NHW adults to have a usual source of care, use preventive services, including cervical cancer screening, and healthcare services. However, after adjustment breast and cervical cancer screening exceeded that of NHW adults. Hispanic adults with LCE fared substantially worse than their Hispanic counterparts with CE in having a usual source of care, use of preventive services, breast and colorectal cancer screening, and healthcare services. After adjustment, use of all cancer screening tests were similar. Eliminating disparities for Hispanic adults will require a multi-pronged approach to address access to healthcare and other social determinants of health, including poverty, employment discrimination, and educational inequities. The public health community can help improve health literacy, address barriers to care, and provide appropriate language assistance at point of care using culturally-competent means to promote greater utilization of preventive services, including demand for and delivery of cancer screenings.

      4. BACKGROUND: We assessed disparities in HPV vaccination coverage by sociodemographic characteristics in the United States. METHODS: Using 2017-March 2020 National Health and Nutrition Examination Survey data, we estimated vaccination coverage of ≥ 1 dose of HPV vaccine by race/ethnicity and poverty, insurance, and nativity status for females and males aged 9-14, 15-19, and 20-29 years. RESULTS: Among those aged 9-14 years, coverage among non-Hispanic Black (NHB), Hispanic, and non-Hispanic Asian (NHA) females (40.0%, 33.6%, 34.0%) and males (27.1%, 35.3%, 30.9%) was higher than non-Hispanic White (NHW) females (26.5%) and males (25.2%). Among those aged 15-19 and 20-29 years, coverage varied among NHB, Hispanic, and NHA compared to NHW females and was lower among NHB, Hispanic, and NHA than NHW males. Coverage was lower among uninsured than insured in most comparisons. CONCLUSIONS: HPV vaccination coverage varied by race/ethnicity and other characteristics. Efforts are needed to increase HPV vaccination coverage in all populations.

    • Healthcare Associated Infections
      1. This case study is part of a series centered on the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) healthcare-associated infection (HAI) surveillance definitions. This specific case study focuses on the application of common surveillance concepts included in the Patient Safety Component, Chapter 9 - Surgical Site Infection Event (SSI). The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions and encourage accurate HAI event determination among Infection Preventionists (IPs).

    • Immunity and Immunization
      1. Autopsy histopathologic cardiac findings in two adolescents following the second COVID-19 vaccine doseexternal icon
        Paddock CD, Reagan-Steiner S, Su JR, Oster ME, Martines RB, Bhatnagar J, Shimabukuro TT.
        Arch Pathol Lab Med. 2022 Apr 8.

      2. Sustaining Maternal and Neonatal Tetanus Elimination (MNTE) in countries that have been validated for elimination - progress and challengesexternal icon
        Yusuf N, Steinglass R, Gasse F, Raza A, Ahmed B, Blanc DC, Yakubu A, Gregory C, Tohme RA.
        BMC Public Health. 2022 Apr 8;22(1):691.
        BACKGROUND: As of October 2021, 47 (80%) of the 59 countries, identified at highest risk for Maternal and Neonatal Tetanus (MNT), had been validated for elimination. We assessed sustainability of MNT elimination (MNTE) in 28 countries that were validated during 2011‒2020. METHODS: We assessed the attainment of the following MNTE sustainability indicators: 1) ≥ 90% coverage with three doses of Diphtheria-Tetanus-Pertussis vaccine (DTP3) among infants < 1 year, 2) ≥ 80% coverage with at least two doses of tetanus toxoid-containing vaccine (TTCV2 +) among pregnant women, 3) ≥ 80% protection at birth (PAB), 4) ≥ 70% skilled birth attendance (SBA), and 4) ≥ 80% first (ANC1) and fourth antenatal care (ANC4) visits. We assessed the introduction of TTCV booster doses. Data sources included the 2020 WHO /UNICEF Joint Reporting Forms, and the latest Demographic and Health Survey (DHS) or Multi-Indicator Cluster Surveys (MICS) for each country, if available. We reviewed literature and used DHS/MICS data to identify barriers to sustaining MNTE. RESULTS: Of 28 assessed countries, 7 (25%) reported ≥ 90% DTP3 coverage, 4 of 26 (16%) reported ≥ 80% TTCV2 + coverage, and 23 of 27 (85%) reported ≥ 80% PAB coverage. Based on DHS/MICS in 15 of the 28 countries, 10 (67%) achieved ≥ 70% SBA delivery, 13 (87%) achieved ≥ 80% ANC1 visit coverage, and 3 (20%) ≥ 80% ANC4 visit coverage. We observed sub-optimal coverage in many countries at the subnational level. The first, second and third booster doses of TTCV respectively have been introduced in 6 (21%), 5 (18%), and 1 (4%) of 28 countries. Only three countries conducted post-MNTE validation assessments. Barriers to MNTE sustainability included: competing program priorities, limited resources to introduce TTCV booster doses and implement corrective immunization in high-risk districts and socio-economic factors. CONCLUSIONS: Despite good performance of MNTE indicators in several countries, MNTE sustainability appears threatened in some countries. Integration and coordination of MNTE activities with other immunization activities in the context of the Immunization Agenda 2030 lifecourse vaccination strategy such as providing tetanus booster doses in school-based vaccination platforms, during measles second dose and HPV vaccination, and integrating MNTE post-validation assessments with immunization program reviews will ensure MNTE is sustained.

      3. Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: Prospective observational studyexternal icon
        Lauring AS, Tenforde MW, Chappell JD, Gaglani M, Ginde AA, McNeal T, Ghamande S, Douin DJ, Talbot HK, Casey JD, Mohr NM, Zepeski A, Shapiro NI, Gibbs KW, Files DC, Hager DN, Shehu A, Prekker ME, Erickson HL, Exline MC, Gong MN, Mohamed A, Johnson NJ, Srinivasan V, Steingrub JS, Peltan ID, Brown SM, Martin ET, Monto AS, Khan A, Hough CL, Busse LW, Ten Lohuis CC, Duggal A, Wilson JG, Gordon AJ, Qadir N, Chang SY, Mallow C, Rivas C, Babcock HM, Kwon JH, Halasa N, Grijalva CG, Rice TW, Stubblefield WB, Baughman A, Womack KN, Rhoads JP, Lindsell CJ, Hart KW, Zhu Y, Adams K, Schrag SJ, Olson SM, Kobayashi M, Verani JR, Patel MM, Self WH.
        BMJ. 2022 09 Mar;376 (no pagination).
        Objectives To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design Case-control study. Setting 21 hospitals across the United States. Participants 11 690 adults (>=18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: Alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). Main outcome measures Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. Results Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). Conclusions mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants. Copyright © Author(s) (or their employer(s)) 2019.

      4. Consistency of self-reported and documented historical influenza vaccination status of US healthcare workersexternal icon
        Regan AK, Wesley MG, Gaglani M, Kim SS, Edwards LJ, Murthy K, Jeddy Z, Naleway AL, Flannery B, Dawood FS, Groom H.
        Influenza Other Respir Viruses. 2022 Apr 12.
        BACKGROUND: Healthcare personnel (HCP) are a priority group for annual influenza vaccination. Few studies have assessed the validity of recall of prior influenza vaccination status among HCP, especially for more than one preceding season. METHODS: Using data from a randomized controlled trial of influenza vaccination among 947 HCP from two US healthcare systems, we assessed agreement between participant self-report and administrative record documentation of influenza vaccination status during the preceding five influenza seasons; kappa coefficients and sensitivity values were calculated. Administrative record documentation was considered the gold standard. Documented vaccination sources included electronic medical records, employee health records, outside immunization providers, and the state immunization information system. RESULTS: Among 683 HCP with prior influenza immunization information, 89.7% (95% CI: 87.2%, 91.9%) of HCP were able to self-report their vaccination status for the season preceding the survey. By the fifth preceding season, 82.6% (95% CI: 79.5%, 85.3%) of HCP were able to self-report. Among HCP who self-reported their vaccination status, agreement between self-report and documented vaccination status ranged from 81.9% (95% CI: 77.2%, 86.7%) for the fifth season to 90.5% (95% CI: 87.2%, 93.9%) for the season preceding interview. HCP who received vaccine for only some of the preceding five seasons (18.3%) more commonly had ≥2 errors in their recall compared with those vaccinated all five preceding seasons (55.7% vs. 4.3%). CONCLUSIONS: Self-reported vaccination status is a reliable source for historical influenza vaccination information among HCP who are consistently vaccinated but less reliable for those with a history of inconsistent vaccination.

      5. In elimination settings, measles antibodies wane following vaccination but not following infection - a systematic review and meta-analysisexternal icon
        Bolotin S, Osman S, Hughes SL, Ariyarajah A, Tricco AC, Khan S, Li L, Johnson C, Friedman L, Gul N, Jardine R, Faulkner M, Hahné SJ, Heffernan JM, Dabbagh A, Rota PA, Severini A, Jit M, Durrheim DN, Orenstein WA, Moss WJ, Funk S, Turner N, Schluter W, Jawad JS, Crowcroft NS.
        J Infect Dis. 2022 Apr 13.
        BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16,822 citations, we identified nine articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received two doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% CI -212.4, -31.1) per year since vaccination over one to five years, 53.7 mIU/mL (95% CI -95.3, -12.2) five to ten years, 33.2 mIU/mL (95% CI -62.6, -3.9) ten to 15 years, and 24.1 mIU/mL (95% CI -51.5,3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after one dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after one or two doses of MCV, or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

      6. COVID-19 vaccine uptake and intentions following US Food and Drug Administration approval of the Pfizer-BioNTech COVID-19 vaccineexternal icon
        Scherer AM, Parker AM, Gidengil CA, Gedlinske AM, Askelson NM, Petersen CA, Lindley MC.
        JAMA Intern Med. 2022 Apr 11.

      7. Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination - PCORnet, United States, January 2021-January 2022external icon
        Block JP, Boehmer TK, Forrest CB, Carton TW, Lee GM, Ajani UA, Christakis DA, Cowell LG, Draper C, Ghildayal N, Harris AM, Kappelman MD, Ko JY, Mayer KH, Nagavedu K, Oster ME, Paranjape A, Puro J, Ritchey MD, Shay DK, Thacker D, Gundlapalli AV.
        MMWR Morb Mortal Wkly Rep. 2022 Apr 8;71(14):517-523.
        Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.

    • Injury and Violence
      1. Injury prevention activities in US schools, School Health Policies and Practices Survey 2014external icon
        Miller GF, Wilson L, Rice K, DePadilla L, Mercado-Crespo M, Jones SE.
        J Sch Health. 2022 Apr 11.
        BACKGROUND: Exposure to injury and violence early in life increases the risk of experiencing injury and violence later in life. In 2019, the top 3 leading causes of death among 15- to 18-year-olds in the United States were unintentional injury, suicide, and homicide. This study examines the extent to which schools promote injury and violence prevention. METHODS: This study examined injury- and violence-related school policies and practices using nationally representative data from the 2014 School Health Policies and Practices Study. The social ecological model served as the theoretical framework to identify level of impact. RESULTS: For many injury-related topics, more than 75% of schools nationwide had relevant policies and practices to address those topics. However, this study showed differences in schools' injury-related policies and practices by urbanicity. CONCLUSIONS: Understanding and identifying gaps in school policies and practices is essential for reducing and preventing the injury and violence children experience. Collecting data on school policies and practices allows for better monitoring and evaluation to determine which are efficacious and aligned with the best available evidence.

    • Laboratory Sciences
      1. Development of a bead-based multiplex assay for use in multianalyte screening and surveillance of HIV, viral hepatitis, syphilis, and herpesexternal icon
        Yufenyuy EL, Vedapuri S, Zheng A, Cooley G, Danavall D, Mayur S, Kodani M, Chen C, Tun Y, Fakile YF, Martin D, Kamili S, Karem K, Parekh BS.
        J Clin Microbiol. 2022 Apr 7:e0234821.
        Diagnostic assays that can simultaneously determine the presence of infection with multiple pathogens are key for diagnosis and surveillance. Current multiplex diagnostic assays are complex and often have limited availability. We developed a simple, multianalyte, pathogen detection assay for screening and serosurveillance using the Luminex Magpix platform that is high throughput and can be helpful in monitoring multiple diseases. The Luminex bead-based 10-plex immunoassay for the detection of HIV-1, HIV-2, Treponema pallidum, hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus 1 (HSV-1), and HSV-2 infections was accomplished by coupling beads with specific antigens to detect IgG antibodies in plasma or serum samples. Each coupled antigen was systematically optimized, and the performance was evaluated using a panel of well-characterized specimens (n = 417) that contained antibodies to HIV-1, HIV-2, T. pallidum, HBV, HCV, HSV-1, and HSV-2. The multiplex assay had a sensitivity of 92.2% (95% Clopper-Pearson confidence interval [CI], 90.2 to 94.0%) and a specificity of 98.1% (95% CI, 97.6 to 98.7%). The sensitivities and specificities for disease-specific biomarker detection ranged from 68.7 to 100% and 95.6 to 100%, respectively. The results showed that the 10-plex immunoassay had an overall agreement of 96.7% (95% CI, 96.7 to 97.3%) with reference tests and a corresponding kappa value of 0.91 (95% CI, 0.90 to 0.93). Kappa values for the individual pathogens ranged from 0.69 to 1.00. The assay is robust and allows the simultaneous detection of antibodies to multiple antigens using a small sample volume in a high-throughput format. This assay has the potential to simplify disease surveillance by providing an alternative to expensive and highly specialized individual tests.

      2. Reference materials for MS-based untargeted metabolomics and lipidomics: a review by the metabolomics quality assurance and quality control consortium (mQACC)external icon
        Lippa KA, Aristizabal-Henao JJ, Beger RD, Bowden JA, Broeckling C, Beecher C, Clay Davis W, Dunn WB, Flores R, Goodacre R, Gouveia GJ, Harms AC, Hartung T, Jones CM, Lewis MR, Ntai I, Percy AJ, Raftery D, Schock TB, Sun J, Theodoridis G, Tayyari F, Torta F, Ulmer CZ, Wilson I, Ubhi BK.
        Metabolomics. 2022 Apr 9;18(4):24.
        INTRODUCTION: The metabolomics quality assurance and quality control consortium (mQACC) is enabling the identification, development, prioritization, and promotion of suitable reference materials (RMs) to be used in quality assurance (QA) and quality control (QC) for untargeted metabolomics research. OBJECTIVES: This review aims to highlight current RMs, and methodologies used within untargeted metabolomics and lipidomics communities to ensure standardization of results obtained from data analysis, interpretation and cross-study, and cross-laboratory comparisons. The essence of the aims is also applicable to other 'omics areas that generate high dimensional data. RESULTS: The potential for game-changing biochemical discoveries through mass spectrometry-based (MS) untargeted metabolomics and lipidomics are predicated on the evolution of more confident qualitative (and eventually quantitative) results from research laboratories. RMs are thus critical QC tools to be able to assure standardization, comparability, repeatability and reproducibility for untargeted data analysis, interpretation, to compare data within and across studies and across multiple laboratories. Standard operating procedures (SOPs) that promote, describe and exemplify the use of RMs will also improve QC for the metabolomics and lipidomics communities. CONCLUSIONS: The application of RMs described in this review may significantly improve data quality to support metabolomics and lipidomics research. The continued development and deployment of new RMs, together with interlaboratory studies and educational outreach and training, will further promote sound QA practices in the community.

      3. Developing a solution for nasal and olfactory transport of nanomaterialsexternal icon
        O'Connell RC, Dodd TM, Clingerman SM, Fluharty KL, Coyle J, Stueckle TA, Porter DW, Bowers L, Stefaniak AB, Knepp AK, Derk R, Wolfarth M, Mercer RR, Boots TE, Sriram K, Hubbs AF.
        Toxicol Pathol. 2022 Apr 13:1926233221089209.
        With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omp(tm3Mom)/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.

    • Maternal and Child Health
      1. Summary of neonatal and maternal transport and reimbursement policies-a 5-year updateexternal icon
        DeSisto CL, Okoroh EM, Kroelinger CD, Barfield WD.
        J Perinatol. 2022 Apr 12.
        OBJECTIVE: To examine the number of states with neonatal and maternal transport and reimbursement policies in 2019, compared with 2014. STUDY DESIGN: We conducted a systematic review of web-based, publicly available information on neonatal and maternal transport policies for each state in 2019. Information was abstracted from rules, codes, licensure regulations, and planning and program documents, then summarized within two categories: transport and reimbursement policies. RESULT: In 2019, 42 states had a policy for neonatal transport and 37 states had a policy for maternal transport, increasing by 8 and 7 states respectively. Further, 31 states had a reimbursement policy for neonatal transport and 11 states for maternal transport, increases of 1 state per category. Overall, the number of states with policies increased from 2014 to 2019. CONCLUSION: The number of state neonatal and maternal transport policies increased; these policies may support provision of care at the most risk-appropriate facilities.

      2. Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenyaexternal icon
        Nyiro JU, Bukusi E, Mwaengo D, Nyaguara A, Nyawanda B, Otieno N, Bigogo G, Murunga N, Widdowson MA, Verani JR, Chaves SS, Mwangudza H, Odundo C, Berkley JA, Nokes DJ, Munywoki PK.
        Wellcome Open Res. 2022 ;7:43.
        Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06-0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07-0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

    • Nutritional Sciences
      1. Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donorsexternal icon
        Addo OY, Mei Z, Hod EA, Jefferds ME, Sharma AJ, Flores-Ayala RC, Spitalnik SL, Brittenham GM.
        Blood Adv. 2022 Apr 11.
        Our objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and two independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20-49 years, who were first-time or reactivated donors in the REDS-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin <25.4 µg/L) and by hemoglobin (serum ferritin <25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin <25.5 µg/L) and hemoglobin (serum ferritin <26.6 µg/L) in a previous study of 5,442 women, 20-49 years, in the U.S. National Health and Nutrition Examination Survey 2003-2018 (NHANES) (p=0.98 and 0.83, respectively). While international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

      2. This study aimed to determine whether higher intakes of sodium, added sugars and saturated fat are prospectively associated with all-cause mortality and cardiovascular disease (CVD) incidence and mortality in a diverse population. The nationally-representative Canadian Community Health Survey (CCHS)-Nutrition 2004 was linked with the Canadian Vital Statistics - Death Database and the Discharge Abstract Database (2004-2011). Outcomes were all-cause mortality and CVD incidence and mortality. There were 1,722 mortality cases within 115,566 person-years of follow-up (median (IQR) of 7.48 (7.22-7.70) years). There was no statistically significant association between sodium density or energy from saturated fat and all-cause mortality or CVD events for all models investigated. The association of usual percentage of energy from added sugars and all-cause mortality was significant in the base model with participants consuming 11.47% of energy from added sugars having 1.34 (95% CI: 1.01-1.77) times higher risk of all-cause mortality compared to those consuming 4.17% of energy from added sugars. Overall, our results did not find statistically significant associations between the three nutrients and risk of all-cause mortality or CVD events at the population level in Canada. Large-scale linked national nutrition datasets may not have the discrimination to identify prospective impacts of nutrients on health measures.

      3. Trends in depression by glycemic status: Serial cross-sectional analyses of the National Health and Nutrition Examination Surveys, 2005-2016external icon
        Chandrasekar EK, Ali MK, Wei J, Narayan KV, Owens-Gary MD, Bullard KM.
        Prim Care Diabetes. 2022 Mar 7.
        AIMS: We examined changes in the prevalence of elevated depressive symptoms among US adults with diabetes, prediabetes, and normal glycemic status during 2005-2016. METHODS: We analyzed data from 32,676 adults in the 2005-2016 National Health and Nutrition Examination Surveys. We defined diabetes as self-reporting a physician diagnosis of diabetes or A1C ≥ 6.5% [48 mmol/mol], and prediabetes as A1C 5.7-6.4% [39-46 mmol/mol]. We used the 9-item Patient Health Questionnaire (PHQ-9) score ≥ 10 or antidepressant use to define 'clinically significant depressive symptoms' (CSDS) and PHQ-9 score ≥ 12 as 'Major Depressive Disorder' (MDD). We calculated prevalence age-standardized to the 2000 US census and used logistic-regression to compute adjusted odds of CSDS and MDD for 2005-2008, 2009-2012, and 2015-2016. We analyzed the prevalence of A1C ≥ 9.0% [75 mmol/mol], systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, non-HDL cholesterol ≥ 130 mg/dL, and current smoking among adults with diagnosed diabetes by depressive status. RESULTS: The prevalence of CSDS increased among individuals with normal glycemic status from 15.0% (13.5-16.2) to 17.3% (16.0-18.7) (p = 0.03) over 2005-2016. The prevalence of CSDS and MDD remained stable among adults with prediabetes (~ 16% and 1%, respectively) and diabetes (~ 26% and ~3%). After controlling for glycemic, sociodemographic, economic, and self-rated health variables, we found 2-fold greater odds of CSDS among unemployed individuals and 3-fold greater odds among those with fair/poor self-rated health across all survey periods. Cardiometabolic care targets for adults with diagnosed diabetes were stable from 2005 to 2016 and similar across depressive status. CONCLUSIONS: One-fourth of adults with diabetes have comorbid CSDS; this prevalence remained stable over 2005-2016 with no change in diabetes care. At the population level, depression does not appear to impact diabetes care, but further research could explore subgroups that may be more vulnerable and could benefit from integrated care that addresses both conditions.

    • Occupational Safety and Health
      1. Roasted coffee emits hazardous volatile organic compounds including diacetyl and 2,3-pentanedione. Workers in non-flavored coffee roasting and packaging facilities might inhale diacetyl and 2,3-pentanedione from roasted coffee above occupational exposure limits depending on their work activities and proximity to the source of emissions. Objectives of this laboratory study were to: (1) investigate factors affecting specific emission rates (SERs) of diacetyl and 2,3-pentanedione from freshly roasted coffee, (2) explore the effect of time on SERs of coffee stored in sealed bags for 10-days, and (3) predict exposures to workers in hypothetical workplace scenarios. Two roast levels (light and dark) and three physical forms (whole bean, coarse ground, and fine ground) were investigated. Particle size for whole bean and ground coffee were analyzed using geometric mean of Feret diameter. Emitted chemicals were collected on thermal desorption tubes and quantified using mass spectrometry analysis. SERs developed here coupled with information from previous field surveys provided model input to estimate worker exposures during various activities using a probabilistic, near-field/far-field model. For freshly roasted coffee, mean SER of diacetyl and 2,3-pentantedione increased with decreasing particle size of the physical form (whole bean < coarse ground < fine ground) but was not consistent with roast levels. SERs from freshly roasted coffee increased with roast level for diacetyl but did not change for 2,3-pentanedione. Mean SERs were greatest for diacetyl at 3.60 mg kg(-1) h(-1) for dark, fine ground and for 2,3-pentanedione at 3.88 mg kg(-1) h(-1) for light, fine ground. For storage, SERs of whole bean remained constant while SERs of dark roast ground coffee decreased and light roast ground coffee increased. Modeling demonstrated that near-field exposures depend on proximity to the source, duration of exposure, and air velocities in the near-field further supporting previously reported chemical air measurements in coffee roasting and packaging facilities. Control of source emissions using local exhaust ventilation especially around grinding activities as well as modification of work practices could be used to reduce exposures in this workforce.

      2. During 2001-2002, the National Institute for Occupational Safety and Health (NIOSH), at the United States Centers for Disease Control and Prevention, collaborated with the Bureau of Labor Statistics (BLS) at the United States Department of Labor to conduct a voluntary survey of U.S. employers regarding the use of respiratory protective devices. In 2003, the survey results were jointly published by NIOSH and BLS. This study highlights and evaluates the scientific impact of the 2001-2002 survey by using Science Impact Framework that provides a historical tracking method with five domains of influence. The authors conducted interviews with original project management as well as a thorough document review and qualitative content analysis of published papers, books, presentations, and other relevant print media. A semi-structured and cross-vetted coding was applied across the five domains: Disseminating Science, Creating Awareness, Catalyzing Action, Effecting Change, and Shaping the Future. The 2001-2002 survey findings greatly enhanced understanding and awareness of respirator use in occupational settings within the United States. It also led to similar surveys in other countries, regulatory initiatives by the Occupational Safety and Health Administration and Mine Safety and Health Administration, and ultimately to a renewed partnership between NIOSH and BLS to collect contemporary estimates of respirator use in the workplace within the United States.

      3. Introduction: Managing and improving occupational safety and health requires evaluating performance. Organizations are encouraged to use both lagging indicators (such as injury rates and costs) and leading indicators (such as questionnaire-assessed safety hazards and management practices) for this purpose, but the association between types of indicators over time can be complex. Longitudinal data can assist in clarifying these associations and increasing indicator utility. Method: Employer data were used to evaluate the reliability and predictive validity of a safety management questionnaire. Employers’ longitudinal questionnaire responses and workers’ compensation (WC) claims data were analyzed using a marginal model with time-dependent covariates. Multivariable Poisson and linear regression analyses with claim rate and logarithmic cost, respectively, as dependent variables were carried out after adjusting for industry sector and size. Questionnaire data were used to evaluate questionnaire scaling properties and to assess generalizability of results. Results: One safety management scale was associated with a better WC outcome as predicted and two scales were unexpectedly associated with poorer WC claim outcomes. Analyses assisted in interpreting the latter results, suggesting that WC outcomes were a stimulus for change in some cases. Twelve hazards assessed on the questionnaire were associated with poorer WC claim outcomes as predicted. Conclusions: This study extends leading indicator research using longitudinal questionnaire and WC claims data from employers. Analyses provided insight into associations between leading and lagging indicators, emphasizing the importance of both for safety improvement. Safety management questionnaire scales were predictive of WC claim outcomes, although support for hazard assessments as leading indicators was stronger. Practical Applications: This study supports the use of employer-completed hazard assessment questionnaires for targeting and prioritizing improvement efforts. Employer-completed safety management scales may be useful for directing improvement efforts, although the conditions under which they are completed, including submission to insurers, require additional consideration. © 2022

      4. OBJECTIVES: To determine whether engineering controls and respiratory protection had measurable short-term impact on indium exposure and respiratory health among current indium-tin oxide production and reclamation facility workers. METHODS: We documented engineering controls implemented following our 2012 evaluation and recorded respirator use in 2012 and 2014. We measured respirable indium (In(resp)) and plasma indium (In(P)) in 2012 and 2014, and calculated change in In(resp) (∆In(resp)) and In(P) (∆In(P)) by the 13 departments. We assessed symptoms, lung function, serum biomarkers of interstitial lung disease (Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D) and chest high-resolution CT at both time points and evaluated workers who participated in both 2012 and 2014 for changes in health outcomes (new, worsened or improved). RESULTS: Engineering controls included installation of local exhaust ventilation in both grinding departments (Rotary and Planar) and isolation of the Reclaim department. Respiratory protection increased in most (77%) departments. ∆In(P) and ∆In(resp) often changed in parallel by department. Among 62 workers participating in both 2012 and 2014, 18 (29%) had new or worsening chest symptoms and 2 (3%) had functional decline in lung function or radiographic progression, but average KL-6 and SP-D concentrations decreased, and no cases of clinical indium lung disease were recognised. CONCLUSIONS: Increased engineering controls and respiratory protection can lead to decreased In(resp), In(P) and biomarkers of interstitial lung disease among workers in 2 years. Ongoing medical monitoring of indium-exposed workers to confirm the longer-term effectiveness of preventive measures is warranted.

    • Parasitic Diseases
      1. Evaluation of the effect of targeted mass drug administration and reactive case detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: A cluster randomized control trialexternal icon
        Abdelmenan S, Teka H, Hwang J, Girma S, Chibsa S, Tongren E, Murphy M, Haile M, Dillu D, Kassim J, Behaksra S, Tadesse FG, Yukich J, Berhane Y, Worku A, Keating J, Zewde A, Gadisa E.
        Trials. 2022 Apr 7;23(1):267.
        BACKGROUND: Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention. METHODS: The study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach. DISCUSSION: This randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04241705 . Registration date: January 27, 2020.

    • Reproductive Health
      1. Preexposure prophylaxis implementation in a reproductive health setting: Perspectives From Planned Parenthood providers and leadersexternal icon
        Wilbourn B, Ogburn DF, Safon CB, Galvao RW, Kershaw TS, Willie TC, Taggart T, Caldwell A, Kaplan C, Phillips N, Calabrese SK.
        Health Promot Pract. 2022 Apr 12:15248399221086616.
        Integrating pregnancy and HIV prevention services would make reproductive health care settings an optimal venue for the promotion and delivery of preexposure prophylaxis (PrEP) to cisgender women. However, these settings have been slow to adopt PrEP. Planned parenthood clinicians and leaders possess critical insight that can help accelerate PrEP implementation in reproductive health care settings and elements of the Consolidated Framework for Implementation Research (i.e., relative priority of the intervention to staff, implementation climate, available resources to implement the intervention, and staff access to knowledge and information about the intervention) can shed light on elements of Planned Parenthood's inner setting that can facilitate PrEP implementation. In this study, individual 60-min interviews were conducted with clinical care team members (n = 10), leadership team members (n = 6), and center managers (n = 2) to explore their perspectives on PrEP implementation and associated training needs. Transcripts were transcribed verbatim and thematically analyzed. Despite having variable PrEP knowledge, participants (100% women, 61% non-Hispanic White) expressed positive attitudes toward implementing PrEP. Barriers and facilitators toward providing PrEP were reported at the structural, provider, and patient levels. Participants desired PrEP training that incorporated culturally competent patient-provider communication. Although participants identified ways that Planned Parenthood uniquely enabled PrEP implementation, barriers must be overcome to optimize promotion and delivery of PrEP to cisgender women.

    • Substance Use and Abuse
      1. INTRODUCTION: State-level monitoring of changes in tobacco product use can inform tobacco control policy and practice. This study examines the state-specific prevalence of current cigarette smoking, smokeless tobacco use, and E-cigarette use and related cigarette quitting behaviors among E-cigarette users during 2017-2018. METHODS: Data from the 2017 and 2018 Behavioral Risk Factor Surveillance System were used to assess state-specific current use of cigarettes, smokeless tobacco, and E-cigarettes among adults aged ≥18 years. Analyzed in 2021, state-specific tobacco product estimates and relative percentage changes between 2017 and 2018 were computed for U.S. states and the District of Columbia. Chi-square tests captured subgroup differences, and logistic regression assessed changes over time. RESULTS: Prevalence of adult current cigarette smoking and smokeless tobacco use varied across states and remained relatively stable during 2017-2018, whereas the prevalence of adult E-cigarette use significantly increased during 2017-2018 among 19 of 36 states that collected Behavioral Risk Factor Surveillance System E-cigarette data in 2018. In all states and the District of Columbia during 2017-2018 combined, the percentage of current cigarette smoking among current E-cigarette users was higher than that of never cigarette smoking; the percentage of attempting to quit cigarette smoking in the past year among dual users of cigarettes and E-cigarettes was >50%. CONCLUSIONS: During 2017-2018, the prevalence of adult current cigarette smoking and smokeless tobacco use varied across states and remained relatively stable, whereas adult E-cigarette use prevalence significantly increased. Comprehensive state-based tobacco prevention and control efforts are warranted to reduce the morbidity and mortality attributed to the use of all tobacco products, including E-cigarettes, among U.S. adults.

    • Telehealth and Telemedicine
      1. Clinical practice changes in monitoring hypertension early in the COVID-19 pandemicexternal icon
        Robbins CL, Ford ND, Hayes DK, Ko JY, Kuklina E, Cox S, Ferre C, Loustalot F.
        Am J Hypertens. 2022 Apr 11.
        BACKGROUND: Clinical practices can use telemedicine and other strategies (e.g., self-measured blood pressure [SMBP]) for remote monitoring of hypertension to promote control while decreasing risk of exposure to SARS-CoV-2, the virus that causes COVID-19. METHODS: The DocStyles survey collected data from primary care providers (PCPs), obstetricians-gynecologists (OB/GYNs), and nurse practitioners/physician assistants (NP/PAs) in fall 2020 (n=1,502). We investigated clinical practice changes for monitoring hypertension that were implemented early in the COVID-19 pandemic and examined differences by clinician and practice characteristics (p<0.05). RESULTS: Overall, 369 (24.6%) of clinicians reported their clinical practices made no changes in monitoring hypertension early in the pandemic, 884 (58.9%) advised patients to monitor blood pressure at home or a pharmacy, 699 (46.5%) implemented or increased use of telemedicine for blood pressure monitoring visits, and 545 (36.3%) reduced the frequency of office visits for blood pressure monitoring. Compared with NP/PAs, PCPs were more likely to advise SMBP monitoring (adjusted prevalence ratios (aPR) 1.28, 95% confidence intervals (CI) 1.11-1.47), implement or increase use of telemedicine (aPR 1.23, 95% CI 1.04-1.46) and reduce the frequency of office visits (aPR 1.37, 95% CI 1.11-1.70) for blood pressure monitoring, and less likely to report making no practice changes (aPR 0.63, 95% CI 0.51-0.77). CONCLUSIONS: We noted variation in clinical practice changes by clinician type and practice characteristics. Clinical practices may need additional support and resources to fully maximize telemedicine and other strategies for remote monitoring of hypertension during pandemics and other emergencies that can disrupt routine health care.

      2. Digital health COVID-19 impact assessment: Lessons learned and compelling needsexternal icon
        Lee P, Abernethy A, Shaywitz D, Gundlapalli AV, Weinstein J, Doraiswamy PM, Schulman K, Madhavan S.
        NAM Perspect. 2022 ;2022.

    • Veterinary Medicine
      1. Screening for viral nucleic acids in the cerebrospinal fluid of dogs with central nervous system inflammationexternal icon
        Barber RM, Li Q, Levine JM, Ruone SJ, Levine GJ, Kenny P, Tong S, Schatzberg SJ.
        Front Vet Sci. 2022 ;9:850510.
        Central nervous system (CNS) inflammation is a common cause of neurological dysfunction in dogs. Most dogs with CNS inflammation are diagnosed with presumptive autoimmune disease. A smaller number are diagnosed with an infectious etiology. Additionally, at necropsy, a subset of dogs with CNS inflammation do not fit previously described patterns of autoimmune disease and an infectious cause is not readily identifiable. Because viral infection is a common cause of meningoencephalitis in people, we hypothesize that a subset of dogs presented with CNS inflammation have an occult viral infection either as a direct cause of CNS inflammation or a trigger for autoimmunity. The goal of this research was to screen cerebrospinal fluid from a large number dogs with CNS inflammation for occult viral infection. One hundred seventy-two dogs with neurological dysfunction and cerebrospinal fluid (CSF) pleocytosis were identified. Of these, 42 had meningoencephalitis of unknown origin, six had steroid-responsive meningitis-arteritis, one had eosinophilic meningoencephalitis, five had documented infection, 21 had and undetermined diagnosis, and 97 had a diagnosis not consistent with primary inflammatory disease of the CNS (e.g., neoplasia). CSF samples were subsequently screened with broadly reactive PCR for eight viral groups: adenovirus, bunyavirus, coronavirus, enterovirus, flavivirus, herpesvirus, paramyxovirus, and parechovirus. No viral nucleic acids were detected from 168 cases screened for eight viral groups, which does not support occult viral infection as a cause of CNS inflammation in dogs. La Crosse virus (LACV) nucleic acids were detected from four cases in Georgia. Subclinical infection was supported in two of these cases but LACV could not be ruled-out as a cause of infection in the other two cases, suggesting further research is warranted to determine if LACV is an occult cause of CNS inflammation in dogs.

      2. Risk factors for death and illness in dogs imported into the United States, 2010-2018external icon
        Pieracci EG, Maskery B, Stauffer K, Gertz A, Brown C.
        Transbound Emerg Dis. 2022 Mar 15.
        CDC estimates 1 million dogs are imported into the United States annually. With the movement of large numbers of animals into the United States the risk of disease importation, especially emerging diseases, and animal welfare issues are of concern. Dogs that arrive to the United States ill or dead are investigated by public health authorities to ensure dogs are not infected with diseases of concern (such as rabies). We identified factors associated with illness and death in imported dogs and estimated the initial investigation cost to public health authorities. Dog importation data from the CDC's Quarantine Activity Reporting System were reviewed from 2010 to 2018. The date of entry, country of origin, port of entry, transportation method and breed were extracted to examine factors associated with illness and death in dogs during international travel. Costs for public health investigations were estimated from data collected by the Bureau of Labor Statistics and Office of Personal Management. Death or illness was more likely to occur in brachycephalic breeds (aOR = 3.88, 95%CI 2.74-5.51). Transportation of dogs via cargo (aOR = 2.41, 95%CI 1.57-3.70) or as checked baggage (aOR = 5.74, 95%CI 3.65-9.03) were also associated with death or illness. On average, 19 dog illnesses or deaths were reported annually from 2010 to 2018. The estimated annual cost to public health authorities to conduct initial public health assessments ranged from $2,071 to $104,648. Current regulations do not provide adequate resources or mechanisms to monitor the rates of morbidity and mortality of imported dogs. There are growing attempts to assess animal welfare and communicable disease importation risks. However, because the responsibility for dogs' health and wellbeing is overseen by multiple agencies it is challenging to coordinate implementation and enforcement measures. A joint federal agency approach to identify interventions that reduce dog morbidity and mortality during flights while continuing to protect US borders from public health and foreign animal disease threats could be beneficial.

    • Zoonotic and Vectorborne Diseases
      1. Duration of West Nile Virus immunoglobulin m antibodies up to 81 months following West Nile Virus disease onsetexternal icon
        Staples JE, Gibney KB, Panella AJ, Prince HE, Basile AJ, Laven J, Sejvar JJ, Fischer M.
        Am J Trop Med Hyg. 2022 Apr 11.
        West Nile virus (WNV) IgM antibodies typically indicate a recent infection. However, WNV IgM antibodies can remain detectable for months to years following illness onset. We found that 23% (11/47) of samples tested with a WNV ELISA and 43% (20/47) of samples tested with WNV microsphere immunoassay (MIA) at 16-19 months following WNV illness onset were positive for IgM antibodies. The proportion of samples testing positive for WNV IgM by ELISA decreased over time, but 5% (2/44) of individuals remained positive at 60-63 months after their acute illness and 4% (2/50) were WNV IgM equivocal at 72-81 months. Testing by MIA showed the same general trend of decreased proportion positive over time though the rates of positivity were higher at most time points compared with the ELISA, including 6% (3/50) of participant's samples identified as IgM positive by MIA at 72-81 months post their acute illness. With the MIA, there also was a high proportion of samples with nonspecific results at each time point; average of 23% across all time points. Clinicians and public health officials should consider these findings along with clinical and epidemiologic data when interpreting WNV IgM antibody test results.

      2. Fatal human alphaherpesvirus 1 infection in free-ranging black-tufted marmosets in anthropized environments, Brazil, 2012-2019external icon
        Wilson TM, Ritter JM, Martines RB, Bullock HA, Fair P, Radford KW, Macedo IL, Sousa DE, Goncalves AA, Romano AP, Passsos PH, Ramos DG, Costa GR, Cavalcante KR, de Melo CB, Zaki SR, Castro MB.
        Emerg Infect Dis. 2022 April;28(4):802-811.
        Human alphaherpesvirus 1 (HuAHV1) causes fatal neurologic infections in captive New World primates. To determine risks for interspecies transmission, we examined data for 13 free-ranging, black-tufted marmosets (Callithrix penicillata) that died of HuAHV1 infection and had been in close contact with humans in anthropized areas in Brazil during 2012-2019. We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. The main clinical findings were neurologic signs, necrotizing meningoencephalitis, and ulcerative glossitis; 1 animal had necrotizing hepatitis. Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. PCR confirmed HuAHV1 infection. These findings illustrate how disruption of the One Health equilibrium in anthropized environments poses risks for interspecies virus transmission with potential spillover not only from animals to humans but also from humans to free-ranging nonhuman primates or other animals. Copyright © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved.

      3. PgtE enzyme of salmonella enterica shares the similar biological roles to plasminogen activator (Pla) in interacting with DEC-205 (CD205), and enhancing host dissemination and infectivity by Yersinia pestisexternal icon
        Li Q, Ye C, Zhao F, Li W, Zhu S, Lv Y, Park CG, Zhang Y, Jiang LY, Yang K, He Y, Cai H, Zhang S, Ding HH, Njiri OA, Tembo JM, Alkraiem AA, Li AY, Sun ZY, Li W, Yan MY, Kan B, Huo X, Klena JD, Skurnik M, Anisimov AP, Gao X, Han Y, Yang RF, Xiamu X, Wang Y, Chen H, Chai B, Sun Y, Yuan J, Chen T.
        Front Immunol. 2022 ;13:791799.
        Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

      4. Plague in disguise: The discovery of occult buboes on surgical procedure or autopsyexternal icon
        Fleck-Derderian S, Cooley KM, Nelson CA.
        Vector Borne Zoonotic Dis. 2022 Apr 11.
        Introduction: Bubonic plague classically manifests as a painful, swollen superficial lymph node (bubo) that is readily apparent on physical examination. However, patients occasionally present with buboes formed in deep lymph nodes, which are difficult to detect and can lead to delays in diagnosis and treatment. To better characterize this phenomenon, we conducted a review of the published literature to identify reports of occult buboes among patients with plague. Methods: Articles were identified from two sources: a systematic review on plague treatment, and a search of the PubMed Central database. Articles were eligible if they described a patient with plague who had (1) no evidence of lymphadenopathy on examination; and (2) at least one bubo discovered during surgery or autopsy. Results: Six patients with occult buboes were identified among 5120 articles screened. The majority were male (n = 4/6) and three were <15 years of age. Fever (n = 6/6), leukocytosis (n = 5/6), and abdominal pain or distention (n = 4/6) were the most common signs and symptoms. Initial diagnoses included other bacterial infections, appendicitis, or acute abdomen. Four patients received at least one antimicrobial effective against Yersinia pestis; however, some experienced delayed treatment due to late diagnosis of plague. Occult buboes were discovered in retroperitoneal (n = 2), inguinal/femoral (n = 2), mesenteric (n = 2), axillary (n = 1), and mediastinal (n = 1) regions. Four of the six patients died. Conclusions: Patients with occult buboes experienced delays in the diagnosis of plague and a high fatality rate. Clinicians in plague-endemic areas should consider the presence of occult buboes among patients with compatible symptoms and exposure history.


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