Issue 16, May 4, 2021

CDC Science Clips: Volume 13, Issue 16, May 4, 2021

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Communicable Diseases
      • Geographic Differences and Social Determinants of Health Among People With HIV Attributed to Injection Drug Use, United States, 2017external icon
        Jin C, Nwangwu-Ike N, Gant Z, Johnson Lyons S, Satcher Johnson A.
        Public Health Rep. 2021 Apr 21:333549211007168.
        OBJECTIVE: People who inject drugs are among the groups most vulnerable to HIV infection. The objective of this study was to describe differences in the geographic distribution of HIV diagnoses and social determinants of health (SDH) among people who inject drugs (PWID) who received an HIV diagnosis in 2017. METHODS: We used data from the National HIV Surveillance System (NHSS) to determine the counts and percentages of PWID aged ≥18 with HIV diagnosed in 2017. We combined these data with data from the US Census Bureau's American Community Survey at the census tract level to examine regional, racial/ethnic, and population-area-of-residence differences in poverty status, education level, income level, employment status, and health insurance coverage. RESULTS: We observed patterns of disparity in HIV diagnosis counts and SDH among the 2666 PWID with a residential address linked to a census tract, such that counts of HIV diagnosis increased as SDH outcomes became worse. The greatest proportion of PWID lived in census tracts where ≥19% of the residents lived below the federal poverty level, ≥18% of the residents had <high school diploma, the median annual household income was <$40 000, and ≥16% of the residents did not have health insurance or a health coverage plan. CONCLUSION: To our knowledge, our study is the first large-scale, census tract-level study to describe SDH among PWID with diagnosed HIV in the United States. The findings of substantial disparities in SDH among people with HIV infection attributed to injection drug use should be further examined. Understanding the SDH among PWID is crucial to reducing disparities in HIV diagnoses in this population.

      • BACKGROUND: Pakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the COVID-19 pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed. METHODS: We updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (i.e., population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs). RESULTS: The modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality. CONCLUSIONS: Using trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV (mOPV2) offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas.

    • Disease Reservoirs and Vectors
      • Insecticide Resistance Patterns and Mechanisms in Aedes aegypti (Diptera: Culicidae) Populations Across Abidjan, Côte d'Ivoire Reveal Emergent Pyrethroid Resistanceexternal icon
        Konan LY, Oumbouke WA, Silué UG, Coulibaly IZ, Ziogba JT, N'Guessan RK, Coulibaly D, Bénié JB, Lenhart A.
        J Med Entomol. 2021 Apr 20.
        From 2008 to 2017, the city of Abidjan, Côte d'Ivoire experienced several Aedes-borne disease epidemics which required control of the vector mosquito population based on the reduction of larval habitats and insecticidal sprays for adult mosquitoes. This study was undertaken to assess the insecticide susceptibility status of Aedes aegypti (Linnaeus) in the city of Abidjan. Immature Ae. aegypti were sampled from several larval habitats within seven communes of Abidjan and reared to adults. Three to five days old F1 emerged adults were tested for susceptibility using insecticide-impregnated papers and the synergist piperonyl butoxide (PBO) following WHO bioassay guidelines. The results showed that Ae. aegypti populations from Abidjan were resistant to 0.1% propoxur, and 1% fenitrothion, with mortality rates ranging from 0% to 54.2%. Reduced susceptibility (93.4-97.5% mortality) was observed to 0.05% deltamethrin, 0.75% permethrin, 0.05% lambda-cyhalothrin, 5% malathion, and 0.8% chlorpyrifos-methyl. This reduced susceptibility varied depending on the insecticide and the collection site. The restoration of mortality when the mosquitoes were pre-exposed to the synergist PBO suggests that increased activity of oxidases could be contributing to resistance. Three kdr mutations (V410L, V1016I, and F1534C) were present in populations tested, with low frequencies for the Leu410 (0.28) and Ile1016 (0.32) alleles and high frequencies for the Cys1534 allele (0.96). These findings will be used to inform future arbovirus vector control activities in Abidjan.

    • Environmental Health
      • Climate and weather directly impact plant phenology, affecting airborne pollen. The objective of this systematic review is to examine the impacts of meteorological variables on airborne pollen concentrations and pollen season timing. Using PRISMA methodology, we reviewed literature that assessed whether there was a relationship between local temperature and precipitation and measured airborne pollen. The search strategy included terms related to pollen, trends or measurements, and season timing. For inclusion, studies must have conducted a correlation analysis of at least 5 years of airborne pollen data to local meteorological data and report quantitative results. Data from peer-reviewed articles were extracted on the correlations between seven pollen indicators (main pollen season start date, end date, peak date, and length, annual pollen integral, average daily pollen concentration, and peak pollen concentration), and two meteorological variables (temperature and precipitation). Ninety-three articles were included in the analysis out of 9,679 articles screened. Overall, warmer temperatures correlated with earlier and longer pollen seasons and higher pollen concentrations. Precipitation had varying effects on pollen concentration and pollen season timing indicators. Increased precipitation may have a short-term effect causing low pollen concentrations potentially due to "wash out" effect. Long-term effects of precipitation varied for trees and weeds and had a positive correlation with grass pollen levels. With increases in temperature due to climate change, pollen seasons for some taxa in some regions may start earlier, last longer, and be more intense, which may be associated with adverse health impacts, as pollen exposure has well-known health effects in sensitized individuals.

    • Food Safety
      • Hypothesis Generation during Foodborne Illness Outbreak Investigationsexternal icon
        White AE, Smith KE, Booth H, Medus C, Tauxe RV, Gieraltowski L, Walter ES.
        Am J Epidemiol. 2021 Apr 20.
        Hypothesis generation is a critical, but challenging, step in a foodborne outbreak investigation. The pathogens that contaminate food have many diverse reservoirs, resulting in seemingly limitless potential vehicles. Identifying a vehicle is particularly challenging for clusters detected through national pathogen-specific surveillance, as cases can be geographically dispersed and lack an obvious epidemiological link. Moreover, state and local health departments may have limited resources to dedicate to cluster and outbreak investigations. These challenges underscore the importance of hypothesis generation during an outbreak investigation. In this review, we present a framework for hypothesis generation focusing on three primary sources of information, typically used in combination: (1) known sources of the pathogen causing illness; (2) person, place, and time characteristics of cases associated with the outbreak (descriptive data); and (3) case exposure assessment. Hypothesis generation can narrow the list of potential food vehicles and focus subsequent epidemiologic, laboratory, environmental, and traceback efforts, ensuring that time and resources are used more efficiently and increasing the likelihood of rapidly and conclusively implicating the contaminated food vehicle.

    • Genetics and Genomics
    • Immunity and Immunization
      • Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Personsexternal icon
        Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, Marquez PL, Olson CK, Liu R, Chang KT, Ellington SR, Burkel VK, Smoots AN, Green CJ, Licata C, Zhang BC, Alimchandani M, Mba-Jonas A, Martin SW, Gee JM, Meaney-Delman DM.
        N Engl J Med. 2021 Apr 21.
        BACKGROUND: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. METHODS: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. RESULTS: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). CONCLUSIONS: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

      • BACKGROUND AND PURPOSE: Herpes zoster (HZ) is associated with increased risk of stroke, and zoster vaccine live (ZVL, Zostavax) reduces the risk of HZ. No study has examined the association between ZVL (Zostavax) and risk of stroke. Present study examined association between receipt of ZVL (Zostavax) and risk of stroke among older US population. METHODS: Our study included 1 603 406 US Medicare fee-for-service beneficiaries aged ≥66 years without a history of stroke and who received ZVL (Zostavax) during 2008 to 2014, and 1 603 406 propensity score-matched unvaccinated beneficiaries followed through to December 31, 2017. We used Cox proportional hazard models to examine association between ZVL (Zostavax) and composite fatal or nonfatal incident stroke outcomes. RESULTS: During a median of 5.1 years follow-up (interquartile range, 3.9-6.7), we documented 64 635 stroke events, including 43 954 acute ischemic strokes and 6727 hemorrhagic strokes, among vaccinated beneficiaries during 8 755 331 person-years. The corresponding numbers among unvaccinated beneficiaries were 73 023, 50 476, and 7276, respectively, during 8 517 322 person-years. Incidence comparing vaccinated to unvaccinated beneficiaries were 7.38 versus 8.57 per 1000 person-years for all stroke, 5.00 versus 5.90 for acute ischemic stroke, and 0.76 versus 0.84 for hemorrhagic stroke (P<0.001 for all difference). Adjusted hazard ratios comparing vaccinated to unvaccinated beneficiaries were 0.84 (95% CI, 0.83-0.85), 0.83 (0.82-0.84), and 0.88 (0.85-0.91) for all stroke, acute ischemic stroke, and hemorrhagic stroke, respectively. The association between ZVL (Zostavax) and risk of stroke appeared to be stronger among younger beneficiaries, beneficiaries who did not take antihypertensive or statin medications and who had fewer comorbid conditions (P<0.05 for interaction) but largely consistent across sex, low-income status, and racial groups. CONCLUSIONS: Among Medicare fee-for-service beneficiaries, receipt of ZVL (Zostavax) was associated with lower incidence of stroke. Our findings may encourage people to get vaccinated against HZ to reduce HZ and HZ-associated stroke risk.

    • Maternal and Child Health
      • Modification of the association between diabetes and birth defects by obesity, National Birth Defects Prevention Study, 1997-2011external icon
        Tinker SC, Gilboa SM, Moore CA, Waller DK, Simeone RM, Kim SY, Jamieson DJ, Botto LD, Fisher SC, Reefhuis J.
        Birth Defects Res. 2021 Apr 19.
        BACKGROUND: Maternal pregestational diabetes and obesity are risk factors for birth defects. Diabetes and obesity often occur together; it is unclear whether their co-occurrence compounds birth defect risk. METHODS: We analyzed 1997-2011 data on 29,671 cases and 10,963 controls from the National Birth Defects Prevention Study, a multisite case-control study. Mothers self-reported height, pregestational weight, and diabetes (pregestational and gestational; analyzed separately). We created four exposure groups: no obesity or diabetes (referent), obesity only, diabetes only, and both obesity and diabetes. We estimated odds ratios (ORs) using logistic regression and the relative excess risk due to interaction (RERI). RESULTS: Among mothers with pregestational obesity without diabetes, modest associations (OR range: 1.1-1.5) were observed for neural tube defects, small intestinal atresia, anorectal atresia, renal agenesis/hypoplasia, omphalocele, and several congenital heart defects. Pregestational diabetes, regardless of obesity, was strongly associated with most birth defects (OR range: 2.0-75.9). Gestational diabetes and obesity had a stronger association than for obesity alone and the RERI (in parentheses) suggested additive interaction for hydrocephaly (1.2; 95% confidence interval [CI]: -0.1, 2.5), tetralogy of Fallot (0.9; 95% CI: -0.01, 1.8), atrioventricular septal defect (1.1; 95% CI: -0.1, 2.3), hypoplastic left heart syndrome (1.1; 95% CI: -0.2, 2.4), and atrial septal defect secundum or not otherwise specified (1.0; 95% CI: 0.3, 1.6; only statistically significant RERI). CONCLUSIONS: Our results do not support a synergistic relationship between obesity and diabetes for most birth defects examined. However, there are opportunities for prevention by reducing obesity and improving glycemic control among women with pregestational diabetes before conception.

    • Nutritional Sciences
      • BACKGROUND: Dietary behavior and nutrient intake patterns among U.S. men and women with inflammatory bowel disease (IBD) are unclear at the population level. METHODS: This cross-sectional study compared dietary intake patterns among U.S. adults (aged ≥18 years) with and without IBD in the 2015 National Health Interview Survey (N = 33,626). Age-standardized weighted prevalences for intake of fruits, vegetables, dairy, whole grain bread, dietary fiber, calcium, total added sugars, sugar-sweetened beverages (SSBs), processed meat, and supplement use were compared between adults with and without IBD by sex. RESULTS: In 2015, an estimated 3 million adults (1.3%) reported IBD. Compared with adults without IBD, adults with IBD were more likely to be older, non-Hispanic white, not currently working, former smokers, and former alcohol drinkers. Overall, dietary behaviors were similar among adults with and without IBD. However, adults with IBD were more likely to take vitamin D supplements (31.5% vs 18.8%) and consume dietary fiber <16.7 grams(g)/day, the amount that 50% of U.S. adults consumed (51.8% vs 44.1%), than those without IBD. Compared with their counterparts, men with IBD were more likely to consume vegetables ≥1 time/day (84.9% vs 76.0%) and take any supplement (59.6% vs 46.0%); women with IBD were more likely to have SSBs ≥2 times/day (26.8% vs 17.8%) and total added sugars ≥14.6 teaspoons(tsp)/day, the amount that 50% of U.S. adults consumed (55.3% vs 46.7%). CONCLUSIONS: Adopting a healthy diet, especially limiting added sugars intake among women with IBD, might be important for the overall health.

    • Reproductive Health
      • Birth companionship in a government health system: a pilot study in Kigoma, Tanzaniaexternal icon
        Chaote P, Mwakatundu N, Dominico S, Mputa A, Mbanza A, Metta M, Lobis S, Dynes M, Mbuyita S, McNab S, Schmidt K, Serbanescu F.
        BMC Pregnancy Childbirth. 2021 Apr 16;21(1):304.
        BACKGROUND: Having a companion of choice throughout childbirth is an important component of good quality and respectful maternity care for women and has become standard in many countries. However, there are only a few examples of birth companionship being implemented in government health systems in low-income countries. To learn if birth companionship was feasible, acceptable and led to improved quality of care in these settings, we implemented a pilot project using 9 intervention and 6 comparison sites (all government health facilities) in a rural region of Tanzania. METHODS: The pilot was developed and implemented in Kigoma, Tanzania between July 2016 and December 2018. Women delivering at intervention sites were given the choice of having a birth companion with them during childbirth. We evaluated the pilot with: (a) project data; (b) focus group discussions; (c) structured and semi-structured interviews; and (d) service statistics. RESULTS: More than 80% of women delivering at intervention sites had a birth companion who provided support during childbirth, including comforting women and staying by their side. Most women interviewed at intervention sites were very satisfied with having a companion during childbirth (96-99%). Most women at the intervention sites also reported that the presence of a companion improved their labor, delivery and postpartum experience (82-97%). Health providers also found companions very helpful because they assisted with their workload, alerted the provider about changes in the woman's status, and provided emotional support to the woman. When comparing intervention and comparison sites, providers at intervention sites were significantly more likely to: respond to women who called for help (p = 0.003), interact in a friendly way (p < 0.001), greet women respectfully (p < 0.001), and try to make them more comfortable (p = 0.003). Higher proportions of women who gave birth at intervention sites reported being "very satisfied" with the care they received (p < 0.001), and that the staff were "very kind" (p < 0.001) and "very encouraging" (p < 0.001). CONCLUSION: Birth companionship was feasible and well accepted by health providers, government officials and most importantly, women who delivered at intervention facilities. The introduction of birth companionship improved women's experience of birth and the maternity ward environment overall.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Recruitment of population-based controls for ALS cases from the National ALS Registryexternal icon
        Bear TM, Malek AM, Foulds A, Rager J, Deperrior SE, Vena JE, Larson TC, Mehta P, Horton DK, Talbott EO.
        Amyotroph Lateral Scler Frontotemporal Degener. 2021 Apr 16:1-7.
        Objective: In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased, population-based controls for comparison to Registry cases (n = 280). Here we report our recruitment methods for controls and the associated response rates and costs. Methods: Eligible ALS cases had complete risk factor survey data, DNA analysis, and blood concentrations of persistent organic pollutants (POPs). Age, sex, and county-matched controls were identified from commercial/consumer databases using a targeted landline phone sample. Eligible controls were consented, surveyed, and mailed the POPs' blood analysis consent form. Once consented, phlebotomy was scheduled. Results: We mailed 3760 recruitment letters for 181 potential case-matches across 42 states between 9/2018 and 3/2020. After making phone contact and determining eligibility, 146 controls agreed to participate (response rate = 11.4%, cooperation rate = 22.8%). To date, 127 controls completed the survey and bloodwork. Though controls were matched to cases on age, sex, and county, unmatched characteristics (e.g. smoking) did not differ statistically. Interviewing and incentive costs are estimated at $211.85 per complete participation. Conclusions: Recruiting matched population-based controls for comparison to cases from the Registry for a study involving completion of a detailed survey and blood specimen provision is relatively feasible and cost effective. This recruitment method could be useful for case-control studies of other rare disorders.

    • Communicable Diseases
      1. Finding, treating and retaining persons with HIV in a high HIV prevalence and high treatment coverage country: Results from the Botswana Combination Prevention Projectexternal icon
        Bachanas P, Alwano MG, Lebelonyane R, Block L, Behel S, Raizes E, Ussery G, Wang H, Ussery F, Pretorius Holme M, Sexton C, Pals S, Lasry A, Del Castillo L, Hader S, Lockman S, Bock N, Moore J.
        PLoS One. 2021 ;16(4):e0250211.
        INTRODUCTION: The scale-up of Universal Test and Treat has resulted in reductions in HIV morbidity, mortality and incidence. However, healthcare system and personal challenges have impacted the levels of treatment coverage achieved. We implemented interventions to improve linkage to care, retention, viral load (VL) coverage and service delivery, and describe the HIV care cascade over the course of the Botswana Combination Prevention Project (BCPP) study. METHODS: BCPP was designed to evaluate the impact of prevention interventions on HIV incidence in 30 communities in Botswana. We followed a longitudinal cohort of newly identified and known HIV-positive persons not on antiretroviral therapy (ART) identified through community-based testing activities through BCPP and referred with appointments to local HIV clinics in 15 intervention communities. Those who did not keep the first or follow-up appointments were tracked and traced through phone and home contacts. Improvements to service delivery models in the intervention clinics were also implemented. RESULTS: A total of 3,657 newly identified or HIV-positive persons not on ART were identified and referred to their local HIV clinic; 90% (3,282/3,657) linked to care and of those, 93% (3,066/3,282) initiated treatment. Near the end of the study, 221 persons remained >90 days late for appointments or missing. Tracing efforts identified 54/3,066 (2%) persons who initiated treatment but died, and 106/3,066 (3%) persons were located and returned to treatment. At study end, 61/3,066 (2%) persons remained missing and were never reached. Overall, 2,951 (98%) persons living with HIV (PLHIV) who initiated treatment were still alive, retained in care and still receiving ART out of the 3,001 persons alive at the end of the study. Of those on ART, 2,854 (97%) had current VL results and 2,784 (98%) of those were virally suppressed at study end. CONCLUSIONS: This study achieved high rates of linkage, treatment initiation, retention and VL coverage and suppression in a cohort of newly identified and known PLHIV not on ART. Tracking and tracing interventions effectively identified those persons who needed more resource intensive follow-up. The interventions implemented to improve service delivery and data quality may have also contributed to high linkage and retention rates. Clinical trial number: NCT01965470.

      2. Acute Cardiovascular Events Associated With Influenza in Hospitalized Adultsexternal icon
        Chow EJ, O'Halloran A, Rolfes MA, Reed C, Garg S.
        Ann Intern Med. 2021 Apr;174(4):583-584.

      3. Aircraft can hold large numbers of persons in close proximity for long periods, which can increase the risk for transmission of infectious disease.* Current CDC guidelines recommend against travel for persons who have not been vaccinated against COVID-19, and a January 2021 CDC order requires masking for all persons while on airplanes.(†)(,)(§) Research suggests that seating proximity on aircraft is associated with increased risk for infection with SARS-CoV-2, the virus that causes COVID-19 (1,2). However, studies quantifying the benefit of specific distancing strategies to prevent transmission, such as keeping aircraft cabin middle seats vacant, are limited. Using bacteriophage MS2 virus as a surrogate for airborne SARS-CoV-2, CDC and Kansas State University (KSU) modeled the relationship between SARS-CoV-2 exposure and aircraft seating proximity, including full occupancy and vacant middle seat occupancy scenarios. Compared with exposures in full occupancy scenarios, relative exposure in vacant middle seat scenarios was reduced by 23% to 57% depending upon the modeling approach. A 23% exposure reduction was observed for a single passenger who was in the same row and two seats away from the SARS-COV-2 source, rather than in an adjacent middle seat. When quantifying exposure reduction to a full 120-passenger cabin rather than to a single person, exposure reductions ranging from 35.0% to 39.4% were predicted. A 57% exposure reduction was observed under the vacant middle seat condition in a scenario involving a three-row section that contained a mix of SARS-CoV-2 sources and other passengers. Based on this laboratory model, a vacant middle seat reduces risk for exposure to SARS-CoV-2 from nearby passengers. These data suggest that increasing physical distance between passengers and lowering passenger density could help reduce potential COVID-19 exposures during air travel. Physical distancing of airplane passengers, including through policies such as middle seat vacancy, could provide additional reductions in SARS-CoV-2 exposure risk.

      4. Investigation and public health response to a COVID-19 outbreak in a rural resort community-Blaine County, Idaho, 2020external icon
        Dunne EM, Maxwell T, Dawson-Skuza C, Burns M, Ball C, Turner K, Hahn CG, Bowyer M, Carter KK, Hudson L.
        PLoS One. 2021 ;16(4):e0250322.
        Blaine County, Idaho, a rural area with a renowned resort, experienced a COVID-19 outbreak early in the pandemic. We undertook an epidemiologic investigation to describe the outbreak and guide public health action. Confirmed cases of COVID-19 were identified from reports of SARS-CoV-2-positive laboratory test results to South Central Public Health District. Information on symptoms, hospitalization, recent travel, healthcare worker status, and close contacts was obtained by medical record review and patient interviews. Viral sequence analysis was conducted on a subset of available specimens. During March 13-April 10, 2020, a total of 451 COVID-19 cases among Blaine County residents (1,959 cases per 100,000 population) were reported, with earliest illness onset March 1. The median patient age was 51 years (interquartile range [IQR]: 37-63), 52 (11.5%) were hospitalized, and 5 (1.1%) died. The median duration between specimen collection and a positive laboratory result was 9 days (IQR: 4-10). Forty-four (9.8%) patients reported recent travel and an additional 37 cases occurred in out-of-state residents. Healthcare workers comprised 56 (12.4%) cases; 33 of whom worked at the only hospital in the county, leading to a 15-day disruption of hospital services. Among 562 close contacts monitored by public health authorities, laboratory-confirmed COVID-19 or compatible symptoms were identified in 51 (9.1%). Sequencing results from 34 specimens supported epidemiologic findings indicating travel as a source of SARS-CoV-2, and identified multiple lineages among hospital workers. Community mitigation strategies included school and resort closure, stay-at-home orders, and restrictions on incoming travelers. COVID-19 outbreaks in rural communities can disrupt health services. Lack of local laboratory capacity led to long turnaround times for COVID-19 test results. Rural communities frequented by tourists face unique challenges during the COVID-19 pandemic. Implementing restrictions on incoming travelers and other mitigation strategies helped reduce COVID-19 transmission early in the pandemic.

      5. COVID-19 Outbreaks in Correctional Facilities with Work-Release Programs - Idaho, July-November 2020external icon
        Dunne EM, Morgan E, Wells-Moore B, Pierson S, Zakroff S, Haskell L, Link K, Powell J, Holland I, Elgethun K, Ball C, Haugen R, Hahn CG, Carter KK, Starr C.
        MMWR Morb Mortal Wkly Rep. 2021 Apr 23;70(16):589-594.
        As of April 16, 2021, U.S. correctional and detention facilities reported 399,631 cases of COVID-19 in incarcerated persons, resulting in 2,574 deaths (1). During July 14-November 30, 2020, COVID-19 was diagnosed in 382 persons incarcerated in Idaho correctional facilities with work-release programs. Work-release programs (which place incarcerated persons in community businesses) have social and economic benefits, but might put participants at increased risk for bidirectional transmission of SARS-CoV-2, the virus that causes COVID-19. The Idaho Department of Correction (IDOC) operates 13 state-run correctional facilities, including six low-security facilities dedicated to work-release programs. This report describes COVID-19 outbreaks in five IDOC facilities with work-release programs,* provides the mitigation strategies that IDOC implemented, and describes the collaborative public health response. As of November 30, 2020, 382 outbreak-related COVID-19 cases were identified among incarcerated persons in five Idaho correctional facilities with work-release programs; two outbreaks were linked to food processing plants. Mitigation strategies that helped to control outbreaks in IDOC facilities with work-release programs included isolation of persons with COVID-19, identification and quarantine of close contacts, mass testing of incarcerated persons and staff members, and temporary suspension of work-release programs. Implementation of public health recommendations for correctional and detention facilities with work-release programs, including mass testing and identification of high-risk work sites, can help mitigate SARS-CoV-2 outbreaks. Incarcerated persons participating in work-release should be included in COVID-19 vaccination plans.

      6. SARS-CoV-2 transmission in a Georgia school district - United States, December 2020-January 2021external icon
        Gettings JR, Gold JA, Kimball A, Forsberg K, Scott C, Uehara A, Tong S, Hast M, Swanson MR, Morris E, Oraka E, Almendares O, Thomas ES, Mehari L, McCloud J, Roberts G, Crosby D, Balajee A, Burnett E, Chancey RJ, Cook P, Donadel M, Espinosa C, Evans ME, Fleming-Dutra KE, Forero C, Kukielka EA, Li Y, Marcet PL, Mitruka K, Nakayama JY, Nakazawa Y, O'Hegarty M, Pratt C, Rice ME, Rodriguez Stewart RM, Sabogal R, Sanchez E, Velasco-Villa A, Weng MK, Zhang J, Rivera G, Parrott T, Franklin R, Memark J, Drenzek C, Hall AJ, Kirking HL, Tate JE, Vallabhaneni S.
        Clin Infect Dis. 2021 Apr 17.
        BACKGROUND: To inform prevention strategies, we assessed the extent of SARS-CoV-2 transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During December 1, 2020-January 22, 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 RT-PCR testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (e.g., sports, elementary school classroom), index case role (i.e., staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1,119 contacts, 688 (63.1%) of whom received testing. Fifty-nine (8.7%) of 679 contacts tested positive; 15 (17.4%) of 86 index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SAR were in indoor, high-contact sports settings (23.8%, 95% confidence interval [CI] 12.7, 33.3), staff meetings/lunches (18.2%, CI 4.5-31.8), and elementary school classrooms (9.5%, CI 6.5-12.5). SAR was higher for staff (13.1%, CI 9.0-17.2) versus student index cases (5.8%, CI 3.6-8.0) and for symptomatic (10.9%, CI 8.1-13.9) versus asymptomatic index cases (3.0%, CI 1.0-5.5). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include COVID-19 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

      7. Multisystem Inflammatory Syndrome in Infants <12 months of Age, United States, May 2020-January 2021external icon
        Godfred-Cato S, Tsang CA, Giovanni J, Abrams J, Oster ME, Lee EH, Lash MK, Le Marchand C, Liu CY, Newhouse CN, Richardson G, Murray MT, Lim S, Haupt TE, Hartley A, Sosa LE, Ngamsnga K, Garcia A, Datta D, Belay ED.
        Pediatr Infect Dis J. 2021 Apr 16.
        BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C. METHODS: Infants of age <12 months with MIS-C were identified by reports to the CDC's MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C. RESULTS: Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C. CONCLUSIONS: Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving.

      8. Incidence, risk factors, and viral etiology of community-acquired acute lower respiratory tract infection among older adults in rural north Indiaexternal icon
        Kumar R, Dar L, Amarchand R, Saha S, Lafond KE, Purakayastha DR, Kumar R, Choudekar A, Gopal G, Dhakad S, Narayan VV, Wahi A, Chhokar R, Lindstrom S, Whitaker B, Choudhary A, Dey AB, Krishnan A.
        J Glob Health. 2021 Apr 3;11:04027.
        BACKGROUND: There are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries. METHODS: We established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls. RESULTS: We followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively. CONCLUSION: In this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

      9. Airport Traveler Testing Program for SARS-CoV-2 - Alaska, June-November 2020external icon
        Ohlsen EC, Porter KA, Mooring E, Cutchins C, Zink A, McLaughlin J.
        MMWR Morb Mortal Wkly Rep. 2021 Apr 23;70(16):583-588.
        Travel can facilitate SARS-CoV-2 introduction. To reduce introduction of SARS-CoV-2 infections, the state of Alaska implemented a program on June 6, 2020, for arriving air, sea, and road travelers that required either molecular testing for SARS-CoV-2, the virus that causes COVID-19, or a 14-day self-quarantine after arrival. The Alaska Department of Health and Social Services (DHSS) used weekly standardized reports submitted by 10 participating Alaska airports to evaluate air traveler choices to undergo testing or self-quarantine, traveler test results, and airport personnel experiences while implementing the program. Among 386,435 air travelers who arrived in Alaska during June 6-November 14, 2020, a total of 184,438 (48%) chose to be tested within 72 hours before arrival, 111,370 (29%) chose to be tested on arrival, and 39,685 (10%) chose to self-quarantine without testing after arrival. An additional 15,112 persons received testing at airport testing sites; these were primarily travelers obtaining a second test 7-14 days after arrival, per state guidance. Of the 126,482 airport tests performed in Alaska, 951 (0.8%) results were positive, or one per 406 arriving travelers. Airport testing program administrators reported that clear communication, preparation, and organization were vital for operational success; challenges included managing travelers' expectations and ensuring that sufficient personnel and physical space were available to conduct testing. Expected mitigation measures such as vaccination, physical distancing, mask wearing, and avoidance of gatherings after arrival might also help limit postarrival transmission. Posttravel self-quarantine and testing programs might reduce travel-associated SARS-CoV-2 transmission and importation, even without enforcement. Traveler education and community and industry partnerships might help ensure success.

      10. Upper Respiratory Tract Co-detection of Human Endemic Coronaviruses and High-density Pneumococcus Associated With Increased Severity Among HIV-Uninfected Children Under 5 Years Old in the PERCH Studyexternal icon
        Park DE, Higdon MM, Prosperi C, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, O'Brien KL, Scott JA, Thea DM, Antonio M, Awori JO, Baillie VL, Bunthi C, Kwenda G, Mackenzie GA, Moore DP, Morpeth SC, Mwananyanda L, Paveenkittiporn W, Ziaur Rahman M, Rahman M, Rhodes J, Sow SO, Tapia MD, Deloria Knoll M.
        Pediatr Infect Dis J. 2021 Apr 19.
        BACKGROUND: Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. METHODS: In the 2011-2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log10 copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site. RESULTS: There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn-, 449 CoV-/HDSpn+ and 3149 CoV-/HDSpn- cases with no significant difference in co-detection frequency by sex (range 51.2%-64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%-34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%-43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%-28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%-7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%-33.3% (P = 0.58) and mortality was 10.0% versus 9.2%-12.9% (P = 0.69). CONCLUSIONS: Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2.

      11. Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United Statesexternal icon
        Washington NL, Gangavarapu K, Zeller M, Bolze A, Cirulli ET, Schiabor Barrett KM, Larsen BB, Anderson C, White S, Cassens T, Jacobs S, Levan G, Nguyen J, Ramirez JM, Rivera-Garcia C, Sandoval E, Wang X, Wong D, Spencer E, Robles-Sikisaka R, Kurzban E, Hughes LD, Deng X, Wang C, Servellita V, Valentine H, De Hoff P, Seaver P, Sathe S, Gietzen K, Sickler B, Antico J, Hoon K, Liu J, Harding A, Bakhtar O, Basler T, Austin B, MacCannell D, Isaksson M, Febbo PG, Becker D, Laurent M, McDonald E, Yeo GW, Knight R, Laurent LC, de Feo E, Worobey M, Chiu CY, Suchard MA, Lu JT, Lee W, Andersen KG.
        Cell. 2021 Mar 30.
        The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

    • Disaster Control and Emergency Services
      1. Lessons learned from implementation of a national hotline for Ebola virus disease emergency preparedness in South Sudanexternal icon
        Lopez VK, Shetty S, Kouch AT, Khol MT, Lako R, Bili A, Ayuen AD, Jukudu A, Kug AA, Mayen AD, Nyawel E, Berta K, Olu O, Clarke K, Bunga S.
        Confl Health. 2021 Apr 15;15(1):27.
        BACKGROUND: The world's second largest Ebola outbreak occurred in the Democratic Republic of Congo from 2018 to 2020. At the time, risk of cross-border spread into South Sudan was very high. Thus, the South Sudan Ministry of Health scaled up Ebola preparedness activities in August 2018, including implementation of a 24-h, toll-free Ebola virus disease (EVD) hotline. The primary purpose was the hotline was to receive EVD alerts and the secondary goal was to provide evidence-based EVD messages to the public. METHODS: To assess whether the hotline augmented Ebola preparedness activities in a protracted humanitarian emergency context, we reviewed 22 weeks of call logs from January to June 2019. Counts and percentages were calculated for all available data. RESULTS: The hotline received 2114 calls during the analysis period, and an additional 1835 missed calls were documented. Callers used the hotline throughout 24-h of the day and were most often men and individuals living in Jubek state, where the national capital is located. The leading reasons for calling were to learn more about EVD (68%) or to report clinical signs or symptoms (16%). Common EVD-related questions included EVD signs and symptoms, transmission, and prevention. Only one call was documented as an EVD alert, and there was no documentation of reported symptoms or whether the person met the EVD case definition. CONCLUSIONS: Basic surveillance information was not collected from callers. To trigger effective outbreak investigation from hotline calls, the hotline should capture who is reporting and from where, symptoms and travel history, and whether this information should be further investigated. Electronic data capture will enhance data quality and availability of information for review. Additionally, the magnitude of missed calls presents a major challenge. When calls are answered, there is potential to provide health communication, so risk communication needs should be considered. However, prior to hotline implementation, governments should critically assess whether their hotline would yield actionable data and if other data sources for surveillance or community concerns are available.

    • Disease Reservoirs and Vectors
      1. Mosquitoes, the major vectors of viruses like dengue, are naturally host to diverse microorganisms, which play an important role in their development, fecundity, immunity, and vector competence. The composition of their microbiota is strongly influenced by the environment, particularly their aquatic larval habitat. In this study, we used 2×300 bp 16s Illumina sequencing to compare the microbial profiles of emerging adult Aedes aegypti mosquitoes and the water collected from common types of aquatic habitat containers in Puerto Rico, which has endemic dengue transmission. We sequenced 141 mosquito and 46 water samples collected from plastic containers, septic tanks, discarded tires, underground trash cans, tree holes, or water meters. We identified 9 bacterial genera that were highly prevalent in the mosquito microbiome, and 77 for the microbiome of the aquatic habitat. The most abundant mosquito-associated bacterial OTUs were from the families Burkholderiaceae, Pseudomonadaceae, Comamonadaceae, and Xanthomonadaceae. Microbial profiles varied greatly between mosquitoes, and there were few major differences explained by container type; however, the microbiome of mosquitoes from plastic containers was more diverse and contained more unique taxa than the other groups. Container water was significantly more diverse than mosquitoes, and our data suggest that mosquitoes filter out many bacteria, with Alphaproteobacteria in particular being far more abundant in water. These findings provide novel insight into the microbiome of mosquitoes in the region and provide a platform to improve our understanding of the fundamental mosquito-microbe interactions.

      2. Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae)external icon
        Fagre AC, Lewis J, Miller MR, Mossel EC, Lutwama JJ, Nyakarahuka L, Nakayiki T, Kityo R, Nalikka B, Towner JS, Amman BR, Sealy TK, Foy B, Schountz T, Anderson J, Kading RC.
        Sci Rep. 2021 Apr 16;11(1):8370.
        Serological cross-reactivity among flaviviruses makes determining the prior arbovirus exposure of animals challenging in areas where multiple flavivirus strains are circulating. We hypothesized that prior infection with ZIKV could be confirmed through the presence of subgenomic flavivirus RNA (sfRNA) of the 3' untranslated region (UTR), which persists in tissues due to XRN-1 stalling during RNA decay. We amplified ZIKV sfRNA but not NS5 from three experimentally-infected Jamaican fruit bats, supporting the hypothesis of sfRNA tissue persistence. Applying this approach to 198 field samples from Uganda, we confirmed presence of ZIKV sfRNA, but not NS5, in four bats representing three species: Eidolon helvum (n = 2), Epomophorus labiatus (n = 1), and Rousettus aegyptiacus (n = 1). Amplified sequence was most closely related to Asian lineage ZIKV. Our results support the use of sfRNA as a means of identifying previous flavivirus infection and describe the first detection of ZIKV RNA in East African bats.

      3. Avian Influenza A Viruses Reassort and Diversify Differently in Mallards and Mammalsexternal icon
        Ganti K, Bagga A, DaSilva J, Shepard SS, Barnes JR, Shriner S, Koelle K, Lowen AC.
        Viruses. 2021 Mar 19;13(3).
        Reassortment among co-infecting influenza A viruses (IAVs) is an important source of viral diversity and can facilitate expansion into novel host species. Indeed, reassortment played a key role in the evolution of the last three pandemic IAVs. Observed patterns of reassortment within a coinfected host are likely to be shaped by several factors, including viral load, the extent of viral mixing within the host and the stringency of selection. These factors in turn are expected to vary among the diverse host species that IAV infects. To investigate host differences in IAV reassortment, here we examined reassortment of two distinct avian IAVs within their natural host (mallards) and a mammalian model system (guinea pigs). Animals were co-inoculated with A/wildbird/California/187718-36/2008 (H3N8) and A/mallard/Colorado/P66F1-5/2008 (H4N6) viruses. Longitudinal samples were collected from the cloaca of mallards or the nasal tract of guinea pigs and viral genetic exchange was monitored by genotyping clonal isolates from these samples. Relative to those in guinea pigs, viral populations in mallards showed higher frequencies of reassortant genotypes and were characterized by higher genotype richness and diversity. In line with these observations, analysis of pairwise segment combinations revealed lower linkage disequilibrium in mallards as compared to guinea pigs. No clear longitudinal patterns in richness, diversity or linkage disequilibrium were present in either host. Our results reveal mallards to be a highly permissive host for IAV reassortment and suggest that reduced viral mixing limits avian IAV reassortment in a mammalian host.

      4. Evidence for natural hybridization and novel Wolbachia strain superinfections in the Anopheles gambiae complex from Guineaexternal icon
        Jeffries CL, Cansado-Utrilla C, Beavogui AH, Stica C, Lama EK, Kristan M, Irish SR, Walker T.
        R Soc Open Sci. 2021 Apr 7;8(4):202032.
        Wolbachia, a widespread bacterium which can influence mosquito-borne pathogen transmission, has recently been detected within Anopheles (An.) species that are malaria vectors in Sub-Saharan Africa. Although studies have reported Wolbachia strains in the An. gambiae complex, apparent low density and prevalence rates require confirmation. In this study, wild Anopheles mosquitoes collected from two regions of Guinea were investigated. In contrast with previous studies, RNA was extracted from adult females (n = 516) to increase the chances for the detection of actively expressed Wolbachia genes, determine Wolbachia prevalence rates and estimate relative strain densities. Molecular confirmation of mosquito species and Wolbachia multilocus sequence typing (MLST) were carried out to analyse phylogenetic relationships of mosquito hosts and newly discovered Wolbachia strains. Strains were detected in An. melas (prevalence rate of 11.6%-16/138) and hybrids between An. melas and An. gambiae sensu stricto (prevalence rate of 40.0%-6/15) from Senguelen in the Maferinyah region. Furthermore, a novel high-density strain, termed wAnsX, was found in an unclassified Anopheles species. The discovery of novel Wolbachia strains (particularly in members, and hybrids, of the An. gambiae complex) provides further candidate strains that could be used for future Wolbachia-based malaria biocontrol strategies.

      5. Ehrlichia chaffeensis causes human monocytic ehrlichiosis, and its principal vector is the Amblyomma americanum tick. The most frequently identified cases of ehrlichiosis come from the southeastern and south central states of the United States. In this study, a molecular typing system was developed that allows for the genetic differentiation of E. chaffeensis isolates. This multi-locus typing system included sequencing and analyzing intergenic regions ECH0033-ECH0035 and ECH0217-ECH0218, plus, variable genes variable length PCR target, 28-kDa, 120-kDa, and hemE. We examined a total of 31 unique isolates from humans and white-tailed deer, and eight DNA samples extracted from infected A. americanum collected from multiple states. This is the largest evaluation of E. chaffeensis isolates and their genotypes. Our findings show that when sequences of all six loci were concatenated and compared, the 39 samples could be separated into 23 genotypes and further grouped into six phylogenetic clades. The data in this study show no clear pattern between the geographic alignment with the genetic differentiation between the strains. As a result, this poses a challenge to understanding the spread of E. chaffeensis in the United States. Interestingly, our findings indicate that multiple strains from distant geographic origins share the same mutations, which suggests that the strains are being moved from one site to another by their hosts or vectors. In addition, we are seeing a northward shift in the lone star tick distribution in the United States. Last, some data also suggest minimal genetic mutations have occurred over time among strains that are within geographical proximity.

    • Environmental Health
      1. This case study focuses on laws and policies used in Baraboo, Wisconsin land redevelopment projects, including the state laws that regulate cleanup of environmentally contaminated properties, the authorizing laws behind the projects, and the policies incorporated into the projects. It does this by highlighting two successful land reuse projects in the City of Baraboo, Wisconsin: the Veolia Property and the Alliant Property. During the redevelopment of these brownfield sites, Baraboo sought remedy to environmental contamination and maintain the community's health. Two grant programs assisted Baraboo in achieving these goals: the Wisconsin Department of Commerce Grant and the Environmental Protection Agency Brownfields Grant. The Brownfields Grant provided Baraboo the ability to conduct health monitoring with assistance from the Agency for Toxic Substances and Disease Registry. These redevelopment projects in Baraboo demonstrate successful interagency and interdisciplinary collaboration, as well as the role of law and policy in removing environmental hazards to reuse properties and promote human health by reducing exposure to environmental contaminants. Baraboo used these laws and policies to revitalize brownfields and account for community health in the process. Other localities and states can use Baraboo's experience as a model to redevelop their own contaminated properties and promote environmental health through the use of their jurisdiction's laws and policies. © 2018 by the Regents of the University of California.

      2. Risks from mercury in anadromous fish collected from Penobscot River, Maineexternal icon
        Melnyk LJ, Lin J, Kusnierz DH, Pugh K, Durant JT, Suarez-Soto RJ, Venkatapathy R, Sundaravadivelu D, Morris A, Lazorchak JM, Perlman G, Stover MA.
        Sci Total Environ. 2021 ;781.
        Levels of total mercury were measured in tissue of six species of migratory fish (alewife, American shad, blueback herring, rainbow smelt, striped bass, and sea lamprey), and in roe of American shad for two consecutive years collected from the Penobscot River or its estuary. The resultant mercury levels were compared to reference doses as established in the U.S. Environmental Protection Agency (EPA) Integrated Risk Information System and wildlife values. Mercury concentrations ranged from 4 μg/kg ww in roe to 1040 μg/kg ww in sea lamprey. Sea lamprey contained the highest amounts of mercury for both seasons of sampling. Current health advisories are set at sufficient levels to protect fishers from harmful consumption of the fish for mercury alone, except for sea lamprey. Based upon published wildlife values for mink, otter, and eagle, consumption of rainbow smelt, striped bass, or sea lamprey poses a risk to mink; striped bass and sea lamprey to otter; and sea lamprey to eagle. For future consideration, the resultant data may serve as a reference point for both human health and wildlife risk assessments for the consumption of anadromous fish. U.S. EPA works with federally recognized Tribes across the nation greatly impacted by restrictions on sustenance fishing, to develop culturally sensitive risk assessments.

    • Epidemiology and Surveillance
      1. Population Size Estimation of Female Sex Workers in Hai Phong, Vietnam: Use of Three Source Capture-Recapture Methodexternal icon
        Nguyen LT, Patel S, Nguyen NT, Gia HH, Raymond HF, Hoang VT, Abdul-Quader AS.
        J Epidemiol Glob Health. 2021 Mar 20.
        INTRODUCTION: A study was conducted in three districts in Hai Phong province, Vietnam to estimate the population size of the Female Sex Workers (FSW) in June-July 2019. METHODS: The procedures included selection of three districts, compilation of a list of accessible venues where FSW congregate, distribution of first unique objects (first capture) and second unique objects (second capture) to FSW in randomly selected venues and implementation of a Mini-Respondent Driven Sampling (mRDS) Survey (third capture). Population size of the FSW was calculated based on the number of FSW in each round, number of FSW 'recaptured' during the second and the third captures. Additionally, personal network size data captured in the mRDS was used to measure the population of FSW within the three districts using Successive Sampling Population Size Estimates (SS-PSE). RESULTS: The total estimated FSWs in the three selected districts, using Three Source Capture-Recapture (3S-CRC) was 958, which is slightly lower than that estimated using SS-PSE - 1192. The 3S-CRC method yielded a provincial estimate of 1911 while the SS-PSE method resulted in a total of 2379 FSW for the province. CONCLUSION: Two techniques produced different PSE at both the district and the province levels and resulted in estimates lower than ones produced using programmatic data. For planning HIV prevention and care service needs among all FSWs, additional studies are needed to estimate the number of sex workers who are not venue-based and use social media platforms to sell services.

    • Food Safety
      1. Notes from the Field: Multistate Outbreak of Escherichia coli O26 Infections Linked to Raw Flour - United States, 2019external icon
        Vasser M, Barkley J, Miller A, Gee E, Purcell K, Schroeder MN, Basler C, Neil KP.
        MMWR Morb Mortal Wkly Rep. 2021 Apr 23;70(16):600-601.

    • Genetics and Genomics
      1. A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatchexternal icon
        Sánchez-Busó L, Yeats CA, Taylor B, Goater RJ, Underwood A, Abudahab K, Argimón S, Ma KC, Mortimer TD, Golparian D, Cole MJ, Grad YH, Martin I, Raphael BH, Shafer WM, Town K, Wi T, Harris SR, Unemo M, Aanensen DM.
        Genome Med. 2021 Apr 19;13(1):61.
        BACKGROUND: Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. METHODS: Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. RESULTS: AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. CONCLUSIONS: The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

    • Healthcare Associated Infections
      1. A cluster of Achromobacter xylosoxidans led to identification of Pseudomonas aeruginosa and Serratia marcescens contamination at a long-term-care facilityexternal icon
        Dunne EM, Hylsky D, Peterson E, Voermans R, Ward A, Turner K, Hahn C, Arduino M, Ball C, Carter KK, Lee JR.
        Am J Infect Control. 2021 Apr 19.
        A cluster of Achromobacter xylosoxidans, an emerging multidrug-resistant aquaphilic bacterium, was identified in three long-term-care facility residents. As Pseudomonas aeruginosa and Serratia marcescens were also present in clinical specimens, we conducted an investigation of all three water-associated species and identified P. aerguniosa and S. marcesens contamination at the facility. Sequencing analysis linked P. aeruginosa to a clinical isolate. Findings highlight the need for precautionary measures to prevent transmission of water-associated multidrug-resistant bacteria in long-term-care facilities.

      2. BACKGROUND: Despite current blood safety measures, transfusion recipients can experience transfusion-related adverse reactions. Monitoring these reactions can aid in understanding the effectiveness of current transfusion safety measures. Data from the National Healthcare Safety Network Hemovigilance Module were used to quantify adverse reaction risk. METHODS: Facilities reporting at least one month of transfused blood components and transfusion-related adverse reactions during January 2013-December 2018 were included. Adverse reaction rates (number per 100,000 components transfused) were calculated for transfused components stratified by component type, collection, and modification methods. RESULTS: During 2013-2018, 201 facilities reported 18,308 transfusion-related adverse reactions among 8.34 million blood components transfused (220/100,000). Adverse reactions were higher among apheresis (486/100,000) and pathogen-reduced platelets (579/100,000) than apheresis red blood cells (197/100,000). Allergic reactions (41%) were most common. There were 23 fatalities and 9% of all adverse reactions were serious (severe, life-threatening, or fatal). Reactions involving pulmonary complications (transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnea) accounted for 35% of serious reactions but 65% of fatalities. Most (76%) of the 37 transfusion-transmitted infections were serious; none involved pathogen-reduced components. CONCLUSIONS: One in 455 blood components transfused was associated with an adverse reaction although the risk of serious reactions (1 in 6224) or transfusion-transmitted infections (1 in 225,440) was lower. Some serious reactions identified were preventable, suggesting additional safety measures may be beneficial. Higher reaction rates identified among pathogen-reduced platelets require further study. These findings highlight the importance of monitoring reactions through national hemovigilance to inform current safety measures and the need for strategies to increase healthcare facility participation.

    • Immunity and Immunization
      1. National and State-Specific Estimates of Settings of Receiving Human Papillomavirus Vaccination Among Adolescents in the United Statesexternal icon
        Lu PJ, Yankey D, Fredua B, Hung MC, Walker TY, Markowitz LE, Elam-Evans LD.
        J Adolesc Health. 2021 Apr 15.
        PURPOSE: Human papillomavirus (HPV) vaccination in the United States has been recommended for girls since 2006 and for boys since 2011. However, settings of receiving HPV vaccination have not been assessed. The purpose of this study is to assess settings of receiving HPV vaccination among adolescents in order to understand what strategies are needed to improve vaccination uptake. METHODS: Data from the 2018 National Immunization Survey-Teen (NIS-Teen) were analyzed to assess place of HPV vaccination overall, and by gender, quarter, and other selected variables among adolescents in the United States. The 2016-2018 NIS-Teen data were combined to assess state-specific place of HPV vaccination. RESULTS: Among vaccinated adolescents aged 13-17 years, a doctor's office was the most common place where HPV vaccination was received (79.2%), followed by clinics, health centers, or other medical facilities (13.5%), health department (4.1%), hospital or emergency room (2.3%), schools (.5%), and pharmacies or stores (.4%). Overall, 99.1% of adolescents aged 13-17 years received HPV vaccination at medical settings and only .9% at nonmedical settings. Reported vaccination in nonmedical settings by state ranged from less than .1% in Delaware, Florida, and New Hampshire to 4.1% in North Dakota, with a median of 1.0%. CONCLUSIONS: Doctor's offices were the most common medical setting for adolescents to receive HPV vaccination. Less than 1% of adolescents received vaccination at nonmedical settings. Continuing work with medical and nonmedical settings to identify and implement appropriate strategies are needed to improve HPV vaccination coverage among adolescents.

    • Informatics
      1. BACKGROUND: Machine learning has the potential to help researchers better understand and close the gap in HIV care delivery in large metropolitan regions such as Mecklenburg County, North Carolina, USA. OBJECTIVES: We aim to identify important risk factors associated with delayed linkage to care for HIV patients with novel machine learning models and identify high-risk regions of the delay. METHODS: Deidentified 2013-2017 Mecklenburg County surveillance data in eHARS format were requested. Both univariate analyses and machine learning random forest model (developed in R 3.5.0) were applied to quantify associations between delayed linkage to care (>30 days after diagnosis) and various risk factors for individual HIV patients. We also aggregated linkage to care by zip codes to identify high-risk communities within the county. RESULTS: Types of HIV-diagnosing facility significantly influenced time to linkage; first diagnosis in hospital was associated with the shortest time to linkage. HIV patients with lower CD4+ cell counts (<200/ml) were twice as likely to link to care within 30 days than those with higher CD4+ cell count. Random forest model achieved high accuracy (>80% without CD4+ cell count data and >95% with CD4+ cell count data) to predict risk of delay in linkage to care. In addition, we also identified top high-risk zip codes of delayed linkage. CONCLUSION: The findings helped public health teams identify high-risk communities of delayed HIV care continuum across Mecklenburg County. The methodology framework can be applied to other regions with HIV epidemic and challenge of delayed linkage to care.

    • Laboratory Sciences
      1. Draft Chromosome Sequences of a Clinical Isolate of the Free-Living Ameba Naegleria fowleriexternal icon
        Ali IK, Kelley A, Joseph SJ, Park S, Roy S, Jackson J, Cope JR, Rowe LA, Burroughs M, Sheth M, Batra D, Loparev V.
        Microbiol Resour Announc. 2021 Apr 15;10(15).
        We present the chromosome sequences of a Naegleria fowleri isolate from a human primary amebic meningoencephalitis (PAM) case. The genome sequences were assembled from Illumina HiSeq and PacBio sequencing data and verified with the optical mapping data. This led to the identification of 37 contigs representing 37 chromosomes in N. fowleri.

      2. Determination of Free Solanesol Levels in Cigarette Filters by Liquid Chromatography-Mass Spectrometryexternal icon
        Bravo Cardenas R, Ngac P, Watson C, Valentin-Blasini L.
        J Anal Toxicol. 2021 Apr 16.
        Solanesol, a naturally occurring constituent of tobacco, has been utilized as a good marker for environmental tobacco smoke particulate and as a non-invasive predictor of mainstream cigarette smoke tar and nicotine intake under naturalistic smoking conditions. A fast and accurate method for measuring free solanesol to assess tobacco smoke exposure is highly desirable. We have developed and validated a new environmentally friendly, high throughput method for measuring solanesol content in discarded cigarette filter butts. The solanesol deposited in the used filters can be correlated with mainstream smoke deliveries of nicotine and total particle matter (TPM) to estimate constituent delivery to smokers. A portion of filter material is removed from cigarette butts after machine smoking, spiked with internal standard solution, extracted, and quantitatively analyzed using reverse phase liquid chromatography coupled to a triple quadrupole mass spectrometer. The new method incorporates a 48-well plate format for automated sample preparation that reduces sample preparation time and solvent use and increases sample throughput 10-fold compared to our previous method. Accuracy and precision were evaluated by spiking known amounts of solanesol on both clean and smoked cigarette butts. Recoveries exceeded 93% at both low and high spiking levels. Linear solanesol calibration curves ranged from 1.9 to 367 µg/butt with a 0.05 µg/butt limit of detection.

      3. Ehrlichiosis, caused by Gram-negative bacteria of the genus Ehrlichia, is considered an emerging infectious disease due to the increasing number of reported cases. Symptoms are non-specific and occur within 1 to 2 weeks following the bite of an infected tick. Confirmatory laboratory diagnostic methods vary in sensitivity and specimen requirements, which can lead to delayed diagnosis. PCR testing serves as an efficient approach to Ehrlichia confirmation in the acute stage of illness. Published assays have been effectively used to detect human ehrlichiosis at limit of detections ranging from 10 to 50 genomic copies (GC) of Ehrlichia DNA. With the discovery of new species capable of human infection, we wanted to develop assays that are sensitive and encompass a wide range of Ehrlichia. Here we developed and validated two sensitive and specific real-time PCR assays (PanE1 and PanE2) for the detection of Ehrlichia species, as well as two real-time PCR assays (ECh2 and ECh4) for the detection of Ehrlichia chaffeensis, specifically. The limit of detection was determined to be 10 GC per reaction with 100% confidence, and as little as 1 GC with lower efficiencies. Accuracy was assessed at 100% correlation. Specificity from exclusivity testing demonstrated that neither the Ehrlichia species assays (n = 60), nor the E. chaffeensis specific assays (n = 64) had cross reactivity with near neighbors or environmental bacteria. A positive predictive value of 100% and a negative predictive value of ≥93% was determined by evaluating banked clinical specimens from 62 patients with the assays. These real-time PCR assays are effective tools to detect human Ehrlichia species during the acute stage of illness. Early detection of Ehrlichia infection by these real-time PCR assays can facilitate diagnosis and treatment.

      4. Strongyloides stercoralis is a soil-transmitted nematode that can cause life-threatening conditions in immunocompromised persons. In the United States, strongyloidiasis should be considered mainly in immigrants, refugees, or travelers. The confirmatory laboratory diagnosis is usually performed by detecting larvae from the stool, duodenal material, and sputum. In persons who are immunocompromised with severe strongyloidiasis, adult worms and eggs can be detected from duodenal material. For serological diagnosis, most assays use crude antigens to detect anti-S. stercoralis IgG. Recently, recombinant proteins such as rSs-NIE-1 and rSs-IR have been used to detect IgG antibodies. We used rSs-NIE-1 and rSs-IR recombinant antigens to develop a biplex Western blot assay to detect the IgG4 antibody in individuals with strongyloidiasis. The sensitivities of rSs-NIE-1 and rSs-IR were 97.4% and 90.8%, respectively, whereas the specificities were 97.6% and 98%, respectively. In conclusion, the biplex rSs-NIE-1 and rSs-IR immunoblot performs well in detecting IgG4 antibody in S. stercoralis-infected persons.

      5. Intranasal powder live attenuated influenza vaccine is thermostable, immunogenic, and protective against homologous challenge in ferretsexternal icon
        Luczo JM, Bousse T, Johnson SK, Jones CA, Pearce N, Neiswanger CA, Wang MX, Miller EA, Petrovsky N, Wentworth DE, Bronshtein V, Papania M, Tompkins SM.
        NPJ Vaccines. 2021 Apr 21;6(1):59.
        Influenza viruses cause annual seasonal epidemics and sporadic pandemics; vaccination is the most effective countermeasure. Intranasal live attenuated influenza vaccines (LAIVs) are needle-free, mimic the natural route of infection, and elicit robust immunity. However, some LAIVs require reconstitution and cold-chain requirements restrict storage and distribution of all influenza vaccines. We generated a dry-powder, thermostable LAIV (T-LAIV) using Preservation by Vaporization technology and assessed the stability, immunogenicity, and efficacy of T-LAIV alone or combined with delta inulin adjuvant (Advax™) in ferrets. Stability assays demonstrated minimal loss of T-LAIV titer when stored at 25 °C for 1 year. Vaccination of ferrets with T-LAIV alone or with delta inulin adjuvant elicited mucosal antibody and robust serum HI responses in ferrets, and was protective against homologous challenge. These results suggest that the Preservation by Vaporization-generated dry-powder vaccines could be distributed without refrigeration and administered without reconstitution or injection. Given these significant advantages for vaccine distribution and delivery, further research is warranted.

      6. Microbial community structure and composition is associated with host species and sex in Sigmodon cotton ratsexternal icon
        Strickland BA, Patel MC, Shilts MH, Boone HH, Kamali A, Zhang W, Stylos D, Boukhvalova MS, Rosas-Salazar C, Yooseph S, Rajagopala SV, Blanco JC, Das SR.
        Anim Microbiome. 2021 Apr 16;3(1):29.
        BACKGROUND: The cotton rat (genus Sigmodon) is an essential small animal model for the study of human infectious disease and viral therapeutic development. However, the impact of the host microbiome on infection outcomes has not been explored in this model, partly due to the lack of a comprehensive characterization of microbial communities across different cotton rat species. Understanding the dynamics of their microbiome could significantly help to better understand its role when modeling viral infections in this animal model. RESULTS: We examined the bacterial communities of the gut and three external sites (skin, ear, and nose) of two inbred species of cotton rats commonly used in research (S. hispidus and S. fulviventer) by using 16S rRNA gene sequencing, constituting the first comprehensive characterization of the cotton rat microbiome. We showed that S. fulviventer maintained higher alpha diversity and richness than S. hispidus at external sites (skin, ear, nose), but there were no differentially abundant genera. However, S. fulviventer and S. hispidus had distinct fecal microbiomes composed of several significantly differentially abundant genera. Whole metagenomic shotgun sequencing of fecal samples identified species-level differences between S. hispidus and S. fulviventer, as well as different metabolic pathway functions as a result of differential host microbiome contributions. Furthermore, the microbiome composition of the external sites showed significant sex-based differences while fecal communities were not largely different. CONCLUSIONS: Our study shows that host genetic background potentially exerts homeostatic pressures, resulting in distinct microbiomes for two different inbred cotton rat species. Because of the numerous studies that have uncovered strong relationships between host microbiome, viral infection outcomes, and immune responses, our findings represent a strong contribution for understanding the impact of different microbial communities on viral pathogenesis. Furthermore, we provide novel cotton rat microbiome data as a springboard to uncover the full therapeutic potential of the microbiome against viral infections.

    • Maternal and Child Health
      1. Characteristics, complications, and sites of bleeding among infants and toddlers less than 2 years of age with VWDexternal icon
        Dupervil B, Abe K, O'Brien SH, Oakley M, Kulkarni R, Thornburg CD, Byams VR, Soucie JM.
        Blood Adv. 2021 Apr 27;5(8):2079-2086.
        Data on infants and toddlers (ITs) with von Willebrand disease (VWD) are lacking. We used data collected in the US Hemophilia Treatment Center Network (USHTCN) to describe birth characteristics, bleeding episodes, and complications experienced by 105 patients with VWD who were <2 years of age. In 68% of the patients, the reason for diagnostic testing was a family history of a bleeding disorder. The mean age at diagnosis was 7 months, with little variation by sex. Patients with type 2 VWD were diagnosed earlier than those with types 1 or 3 (P = .04), and those with a family history were diagnosed ∼4 months earlier than those with none (P < .001). Among the patients who experienced a bleeding event (70%), oral mucosa was the most common site of the initial bleeding episode (32%), followed by circumcision-related (12%) and intracranial/extracranial bleeding (10%). Forty-one percent of the initial bleeding events occurred before 6 months of age, and 68% of them occurred before the age of 1 year. Approximately 5% of the cohort experienced an intracranial hemorrhage; however, none was associated with delivery at birth. Bleeding patterns and rates were similar by sex (P = .40) and VWD type (P = .10). Forty-seven percent were treated with plasma-derived von Willebrand factor VIII concentrates. The results of this study indicate that a high percentage of ITs diagnosed with VWD and receiving care within the multidisciplinary structure of the USHTCN have a family history of VWD. In addition, bleeding events such as circumcision-related, oropharyngeal, and intracranial or extracranial episodes are common and are leading indicators for treatment.

      2. Venlafaxine prescription claims among insured women of reproductive age and pregnant women, 2011-2016external icon
        Summers AD, Anderson KN, Ailes EC, Grosse SD, Bobo WV, Tepper NK, Reefhuis J.
        Birth Defects Res. 2021 Apr 16.
        BACKGROUND: Some studies have reported associations between prenatal use of venlafaxine, a serotonin-norepinephrine reuptake inhibitor used for depressive and anxiety disorders, and some birth defects. We described the prevalence of venlafaxine prescription claims among privately insured women of reproductive age and pregnant women. METHODS: Venlafaxine prescription claims were examined using the IBM MarketScan Commercial Databases. We included women of reproductive age (15-44 years) who had ≤45 days of lapsed enrollment during the calendar year of interest (2011-2016) in a non-capitated healthcare plan sponsored by a large, self-insured employer with prescription drug coverage and no mental health service carve-out. Annual cohorts of pregnant women were identified among eligible women of reproductive age via pregnancy diagnosis and procedure codes. Venlafaxine prescriptions were identified via National Drug Codes in outpatient pharmacy claims and we estimated the annual proportion of women with venlafaxine claims by pregnancy trimester (pregnant women only), age, and Census division. RESULTS: Each year during 2011-2016, approximately 1.2% of eligible reproductive-aged and 0.3% of eligible pregnant women filled a venlafaxine prescription. Among pregnant women, the proportion with venlafaxine claims was highest during the first trimester and decreased during the second and third trimesters. Small temporal increases in venlafaxine claims were observed for reproductive-aged and pregnant women, with the largest among women aged 15-19 years. CONCLUSIONS: Venlafaxine prescription claims were low among women of reproductive age and pregnant women during 2011-2016, with some increasing use over time among women aged 15-19 years.

    • Occupational Safety and Health
      1. Mexican immigrants suffer a disproportionately large number of work-related injuries and deaths given their share of the workforce. Barriers of language, culture, and mistrust are often cited as factors that complicate efforts to reach these workers with occupational safety and health (OSH) interventions. By partnering with the Mexican government and its consulate network in the United States, researchers from the National Institute for Occupational Safety and Health were able to assess the impact of four different information dissemination approaches (posters, passively distributed brochures, actively distributed brochures, and video kiosks) in Spanish in a five-phase study. Exit interviews conducted with Mexicans seeking consular services indicated that while nearly all respondents considered OSH to be of importance, significant differences in impact measures, such as noticing the materials and liking of content, were found when comparing the different approaches. Despite these differences, even the least effective approaches were noticed by large numbers of individuals and significantly increased their stated behavioral intentions regarding OSH. Considering all materials together, significantly more participants reported liking the materials (p < 0.001) than did not, learning something new (p < 0.01), trusting the information (p < 0.05), intending to seek out additional OSH information (p < 0.01), and intending to speak to their bosses about OSH (p < 0.05). These findings contribute to building an evidence base for moving research knowledge into practice, which is an essential, but often overlooked, element of occupational safety and health research, particularly among workers from underserved communities.

      2. Analysis of single nucleotide polymorphisms in chronic beryllium diseaseexternal icon
        Frye BC, Gaede KI, Saltini C, Rossman MD, Monos DS, Rosenman KD, Schuler CR, Weston A, Wegner R, Noth R, Zissel G, Schreiber S, Nothnagel M, Müller-Quernheim J.
        Respir Res. 2021 Apr 16;22(1):107.
        Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Even though one of largest cohorts of beryllium-exposed persons was analysed, no statistically relevant association between any SNP and CBD could be verified. Notably, some SNPs exhibit inverse OR for beryllium sensitization and CBD with nominally statistical significance, which allows hypothesizing about pathophysiological role of genes for the disease triggering and development.

      3. Workers' Compensation Claim Rates and Costs for Musculoskeletal Disorders Related to Overexertion Among Construction Workers - Ohio, 2007-2017external icon
        Kaur H, Wurzelbacher SJ, Bushnell PT, Grosch JW, Tseng CY, Scholl JC, Meyers AR, Lampl M.
        MMWR Morb Mortal Wkly Rep. 2021 Apr 23;70(16):577-582.
        Overexertion is a leading cause of work-related musculoskeletal disorders (WMSDs) among construction workers. Nearly 90% of construction jobs require manual handling of materials for approximately one half of the worker's time (1). In 2015, overexertion from lifting and lowering materials caused 30% of WMSDs among construction workers; overexertion involving pushing, pulling, holding, carrying, and catching materials caused an additional 37% of WMSDs (1). This study examined the rate and cost of WMSD claims from overexertion among Ohio construction workers during 2007-2017. Workers' compensation claims related to overexertion that were submitted to the Ohio Bureau of Worker's Compensation (OHBWC) by workers in the construction industry for injuries and illnesses occurring during 2007-2017 were analyzed. Rates and costs of allowed claims were measured by age group. Workers aged 35-44 years experienced the highest claim rate: 63 per 10,000 full-time employees (FTEs) for WMSDs from overexertion. However, claims by workers aged 45-54 years and 55-64 years were more costly on average and resulted in more days away from work. Ergonomic design improvements and interventions are needed to ensure that the majority of construction workers can safely perform jobs throughout their careers. Age-specific WMSD prevention and risk communication efforts also might be helpful.

    • Parasitic Diseases
      1. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single-arm, multicentre, therapeutic efficacy studyexternal icon
        Uwimana A, Umulisa N, Venkatesan M, Svigel SS, Zhou Z, Munyaneza T, Habimana RM, Rucogoza A, Moriarty LF, Sandford R, Piercefield E, Goldman I, Ezema B, Talundzic E, Pacheco MA, Escalante AA, Ngamije D, Mangala JN, Kabera M, Munguti K, Murindahabi M, Brieger W, Musanabaganwa C, Mutesa L, Udhayakumar V, Mbituyumuremyi A, Halsey ES, Lucchi NW.
        Lancet Infect Dis. 2021 Apr 14.
        BACKGROUND: Partial artemisinin resistance is suspected if delayed parasite clearance (ie, persistence of parasitaemia on day 3 after treatment initiation) is observed. Validated markers of artemisinin partial resistance in southeast Asia, Plasmodium falciparum kelch13 (Pfkelch13) R561H and P574L, have been reported in Rwanda but no association with parasite clearance has been observed. We aimed to establish the efficacy of artemether-lumefantrine and genetic characterisation of Pfkelch13 alleles and their association with treatment outcomes. METHODS: This open-label, single-arm, multicentre, therapeutic efficacy study was done in 2018 in three Rwandan sites: Masaka, Rukara, and Bugarama. Children aged 6-59 months with P falciparum monoinfection and fever were eligible and treated with a 3-day course of artemether-lumefantrine. Treatment response was monitored for 28 days using weekly microscopy screenings of blood samples for P falciparum. Mutations in Pfkelch13 and P falciparum multidrug resistance-1 (Pfmdr1) genes were characterised in parasites collected from enrolled participants. Analysis of flanking microsatellites surrounding Pfkelch13 was done to define the origins of the R561H mutations. The primary endpoint was PCR-corrected parasitological cure on day 28, as per WHO protocol. FINDINGS: 228 participants were enrolled and 224 (98·2%) reached the study endpoint. PCR-corrected efficacies were 97·0% (95% CI 88-100) in Masaka, 93·8% (85-98) in Rukara, and 97·2% (91-100) in Bugarama. Pfkelch13 R561H mutations were present in 28 (13%) of 218 pre-treatment samples and P574L mutations were present in two (1%) pre-treatment samples. 217 (90%) of the 240 Pfmdr1 haplotypes observed in the pretreatment samples, had either the NFD (N86Y, Y184F, D1246Y) or NYD haplotype. Eight (16%) of 51 participants in Masaka and 12 (15%) of 82 participants in Rukara were microscopically positive 3 days after treatment initiation, which was associated with pre-treatment presence of Pfkelch13 R561H in Masaka (p=0·0005). Genetic analysis of Pfkelch13 R561H mutations suggest their common ancestry and local origin in Rwanda. INTERPRETATION: We confirm evidence of emerging artemisinin partial resistance in Rwanda. Although artemether-lumefantrine remains efficacious, vigilance for decreasing efficacy, further characterisation of artemisinin partial resistance, and evaluation of additional antimalarials in Rwanda should be considered. FUNDING: The US President's Malaria Initiative. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

    • Public Health Leadership and Management
      1. Leading Organizational Change: Improved Leadership Behaviors Among Public Health Leaders After Receiving Multirater Feedback and Coachingexternal icon
        Spears-Jones C, Myles R, Porch T, Parris S, Ivy-Knudsen M, Dean HD.
        Workplace Health Saf. 2021 Apr 22:21650799211001728.
        BACKGROUND: Leading Change is one of five Executive Core Qualifications (ECQs) used in developing leaders in the federal government. Leadership development programs that incorporate multirater feedback and executive coaching are valuable in developing competencies to lead change. METHODS: We examined the extent by which coaching influenced Leading Change competencies and identified effective tools and resources used to enhance the leadership capacity of first- and midlevel leaders at Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis Prevention. Data included qualitative data collected via semi-structured interviews that focused on leadership changes made by leaders in the Coaching and Leadership Initiative (CaLI), a leadership development program for Team Leads and Branch Chiefs. FINDINGS: Ninety-six participants completed leadership coaching; 94 (98%) of whom completed one or more interviews. Of those 94 respondents, 74 (79%) reported improvements in their ability to lead change in 3 of 4 leading change competencies: creativity and innovation, flexibility, and resilience. All respondents indicated tools and resources that were effective in leading change: 49 (52%) participated in instructor-led activities during their CaLI experience; 33 (35%) experiential activities; 94 (100%) developmental relationships, assessment, and feedback; and 25 (27%) self-development. CONCLUSIONS/APPLICATION TO PRACTICE: First- and midlevel leaders in a public health agency benefitted from using leadership coaching in developing competencies to lead organizational change. Leadership development programs might benefit from examining Leading Change competencies and including instructor-led and experiential activities as an additional component of a comprehensive leadership development program.

    • Reproductive Health
      1. Factors associated with age of first sex among women screened for an observational contraceptive vaginal ring study in Kisumu, Kenya, 2014external icon
        Ondenge K, Gvetadze R, Otieno G, Gust DA, McLellan-Lemal E.
        Afr J Reprod Health. 2021 ;25(1):101-113.
        Sex at an early age can have later life negative health outcomes. Insights on early sexual activity may help in the development of future health-promotion products and interventions related to pregnancy and sexually transmitted infections (STIs) prevention. Among Kenyan women participating in a contraceptive vaginal ring study, we determined: (1) the proportion with first sex at 15 years (early sex) and (2) factors associated with early sex. Baseline data collection and testing for pregnancy, STIs, and HIV were undertaken. A log-binomial or a modified Poisson regression was used to estimate univariable prevalence ratios and multivariable adjusted prevalence ratios (aPRs). Among 332 women aged 18-34 years, the median age of first sex was 16 years, with 40.1% experiencing early sex. Overall, 29.8% reported an older first sex partner (5 years); 83.9% indicated lack of readiness or intentions at first sex; and 56.2% received money, gifts, or favors as part of first sex. Early sex was more prevalent among inherited widows (a Luo cultural practice, aPR 1.49), gift recipients (aPR 1.38), women with a forced/unwanted sex history (aPR 1.42), or those with a partner of unknown or positive HIV status in the past 3 months (aPR 1.45). Sex before or at the age 15 may be associated with higher sexual risk behaviors. Complex power and gender relations may additionally influence exposure to sexual risk in our research setting.

      2. Effect of distance to health facilities and access to contraceptive services among urban Turkish womenexternal icon
        Sato R, Rohr J, Huber S, Esmer Y, Okçuoğlu BA, Karadon D, Shah I, Canning D.
        Eur J Contracept Reprod Health Care. 2021 Apr 20:1-9.
        OBJECTIVE: Worldwide unmet need for contraception remains high at 21.6%. As access to health facilities is one of the potential barriers to contraceptive uptake, the aim of our study was to evaluate the effect of distance to a health facility, according to its service availability, on contraceptive uptake among married Turkish women. METHODS: To calculate respondents' distance to a health facility, we used data from a household survey conducted among married women, as well as data from a health facility survey conducted among the facilities that were visited for contraceptive services by the respondents. The data were collected from the Istanbul area of Turkey under the Willows Impact Evaluation project in 2018. Health facilities were categorised according to contraceptive availability and the accurate distance from respondents' homes to each type of health facility was calculated. Logistic regression was used to estimate the effect of distance to each type of health facility on uptake of each type of contraception. RESULTS: The prevalence of overall contraceptive use among urban Turkish women was 71.9%. The most common method was withdrawal (32.5%), followed by the intrauterine device (IUD) (14.9%) and male condoms (12.4%). Distance to a health facility that did not provide long-acting contraception was not associated with any type of contraceptive use. On the other hand, distance to a health facility that provided long-acting contraception was negatively associated with the use of long-acting methods such as the IUD but was positively associated with the use of short-acting contraception such as condoms. CONCLUSION: The effect of distance to a health facility on contraceptive use significantly differed according to contraceptive availability at the facility. Further distance to a health facility that provided long-acting contraception decreased the use of long-acting contraception but had a substitute effect on the use of short-acting contraception. We conclude that when women face an accessibility barrier to the provision of long-acting contraception, they modify their behaviour by shifting from long- to short-acting contraception, which is less effective.

    • Substance Use and Abuse
      1. BACKGROUND: Smokeless tobacco (SLT) use is associated with multiple adverse health effects. It is prominent in Bangladesh, India, and Pakistan, but disparities in use within and across these countries are not well documented or understood. This study assessed the prevalence, patterns, and correlates of SLT use in these three countries. METHOD: Data came from the Global Adult Tobacco Survey, a household survey of adults aged ≥15 years. Data were collected in 2014 (Pakistan), 2017 (Bangladesh), and India (2016-2017). Current SLT use (nasal or oral use) was defined as reported SLT use daily or less than daily at the time of the survey. Prevalence of both overall and specific SLT types were assessed. Multivariate logistic regression was used to assess correlates of SLT use. RESULTS: Overall, SLT use among adults ≥15 years of age was 20.6% in Bangladesh, 21.4% in India, and 7.7% in Pakistan, corresponding to 22.0 million SLT users in Bangladesh, 199.4 million in India, and 9.6 million in Pakistan. Among current tobacco users overall, the percentage of those who used SLT was 58.4% (CI: 56.0-60.7) in Bangladesh, 74.7% (CI: 73.4-76.0) in India, and 40.3% (CI: 36.2-44.5) in Pakistan. The most commonly used oral SLT product was Zarda (14.5%) in Bangladesh, Khaini (11.2%) in India, and Naswar (5.1%) in Pakistan. Females had greater odds of SLT use than males in Bangladesh, but lower odds of SLT use than males in India and Pakistan. In all three countries, the odds of SLT use was higher among those 25 years and older, lower education, lower wealth index, and greater exposure to SLT marketing. CONCLUSION: An estimated 231 million adults aged 15 years or older currently use SLT in Bangladesh, India, and Pakistan, comprising 40.3%-74.7% of overall tobacco product use in these countries. Moreover, marked variations in SLT use exist by population groups. Furthermore, exposure to pro-SLT marketing was found to be associated with higher SLT use compared to non-exposed. It is important that tobacco control strategies address all forms of tobacco product use, including SLT.

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