Issue 6, February 16, 2021

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CDC Science Clips: Volume 13, Issue 6, February 16, 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. 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. Developing epilepsy training capacity for primary care providers using the project ECHO telementoring modelexternal icon
        McDonald SB, Privitera M, Kakacek J, Owens S, Shafer P, Kobau R.
        Epilepsy Behav. 2021 Feb 4;116:107789.
        BACKGROUND: Primary care providers (PCPs) provide a large proportion of care for people with epilepsy (PWE) and need regular training for updates. However, PCPs treat patients in so many therapeutic areas that epilepsy often becomes a less important concern. We used an established telementoring program, Project ECHO (Extension for Community Healthcare Outcomes), and combined epilepsy education with general neurology topics to generate more interest among PCPs. METHODS: We offered 20 one-hour webinar sessions over a two-year period, each consisting of a panel of neurology experts, with a combination of case presentations, a 20-minute didactic presentation, and live, interactive question and answer. Attendees logged in from their own computers or phones, and all presentations were archived online for future viewing. Interviews with PCPs indicated a combination of epilepsy and general neurology topics would be better received, so epilepsy topics alternated monthly with general neurology topics (e.g., headache, stroke, and dementia). Session evaluation included participants' comfort in treating patients with neurological disorders and confidence in knowledge of the topic area. RESULTS: After the second session, mean attendance was 27.5 participants (range 15-38), with a total of 164 unique individual participants. Attendees were a mix of mostly regional, some out of state, and a few international learners, including practicing PCPs, trainees, and nurse practitioners. Archived presentations on our website were viewed 212 times; seizure topics were the most viewed. Mean evaluation scores for relevance, value, and increased knowledge were all in the "agree to strongly agree" range. Over 97% of respondents reported greater interest in improving care of patients with epilepsy or neurological disorders, and over 98% reported greater comfort and self-efficacy when treating patients with these conditions. Only eight cases were submitted for review prior to the sessions. CONCLUSIONS: We successfully piloted a telementoring program using Project ECHO methodology, which was effective in educating PCPs about epilepsy treatment. Combining epilepsy and other neurology topics was an effective strategy in garnering interest among PCPs, but additional methods are needed to encourage participants to present their own cases.

      2. Assessing impact of HPV vaccination on cervical cancer incidence among women aged 15-29 years in the United States, 1999-2017: An ecologic studyexternal icon
        Mix JM, Van Dyne EA, Saraiya M, Hallowell BD, Thomas CC.
        Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):30-37.
        BACKGROUND: To date, the impact of the human papillomavirus (HPV) vaccine on invasive cervical cancers in the United States has not been documented due, in part, to the time needed for cancer to develop and to recent changes to cervical cancer screening guidelines and recommendations, which complicate data interpretation. METHODS: We examined incidence rates of cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) among women aged 15-29 years diagnosed during 1999-2017 using population-based cancer registry data covering 97.8% of the U.S. POPULATION: Trends were stratified by age and histology. The annual percent change in cervical cancer incidence per year was calculated using joinpoint regression. RESULTS: During 1999-2017, SCC rates decreased 12.7% per year among women aged 15-20 years, 5.5% among women aged 21-24 years, and 2.3% among women aged 25-29 years. The declines in SCC rates were largest among women aged 15-20 years during 2010-2017, with a decrease of 22.5% per year. Overall, AC rates decreased 4.1% per year among women aged 15-20 years, 3.6% per year among women aged 21-24 years, and 1.6% per year among women aged 25-29 years. AC rates declined the most among women aged 15-20 years during 2006-2017, decreasing 9.4% per year. CONCLUSIONS: Since HPV vaccine introduction, both SCC and AC incidence rates declined among women aged 15-20 years, a group not typically screened for cervical cancer, which may suggest HPV vaccine impact. IMPACT: Timely vaccination and improved screening and follow-up among recommended age groups could result in further reductions in invasive cervical cancer.

      3. Trends in predominant causes of death in individuals with and without diabetes in England from 2001 to 2018: an epidemiological analysis of linked primary care recordsexternal icon
        Pearson-Stuttard J, Bennett J, Cheng YJ, Vamos EP, Cross AJ, Ezzati M, Gregg EW.
        Lancet Diabetes Endocrinol. 2021 Feb 3.
        BACKGROUND: The prevalence of diabetes has increased in the UK and other high-income countries alongside a substantial decline in cardiovascular mortality. Yet data are scarce on how these trends have changed the causes of death in people with diabetes who have traditionally died primarily of vascular causes. We estimated how all-cause mortality and cause-specific mortality in people with diabetes have changed over time, how the composition of the mortality burden has changed, and how this composition compared with that of the non-diabetes population. METHODS: In this epidemiological analysis of primary care records, we identified 313 907 individuals with diabetes in the Clinical Practice Research Datalink, a well described primary care database, between 2001 to 2018, and linked these data to UK Office for National Statistics mortality data. We assembled serial cross sections with longitudinal follow-up to generate a mixed prevalence and incidence study population of patients with diabetes. We used discretised Poisson regression models to estimate annual death rates for deaths from all causes and 12 specific causes for men and women with diabetes. We also identified age-matched and sex matched (1:1) individuals without diabetes from the same dataset and estimated mortality rates in this group. FINDINGS: Between Jan 1, 2001, and Oct 31, 2018, total mortality declined by 32% in men and 31% in women with diagnosed diabetes. Death rates declined from 40·7 deaths per 1000 person-years to 27·8 deaths per 1000 person-years in men and from 42·7 deaths per 1000 person-years to 29·5 deaths per 1000 person-years in women with diagnosed diabetes. We found similar declines in individuals without diabetes, hence the gap in mortality between those with and without diabetes was maintained over the study period. Cause-specific death rates declined in ten of the 12 cause groups, with exceptions in dementia and liver disease, which increased in both populations. The large decline in vascular disease death rates led to a transition from vascular causes to cancers as the leading contributor to death rates in individuals with diagnosed diabetes and to the gap in death rates between those with and without diabetes. INTERPRETATION: The decline in vascular death rates has been accompanied by a diversification of causes in individuals with diagnosed diabetes and a transition from vascular diseases to cancers as the leading contributor to diabetes-related death. Clinical and preventative approaches must reflect this trend to reduce the excess mortality risk in individuals with diabetes. FUNDING: Wellcome Trust.

    • Communicable Diseases
      1. Purpose: We assessed the association of receipt of medical gender affirmation services (e.g., hormones, surgery) with HIV and other sexually transmitted disease (STD) prevention and knowledge indicators among transgender youth. Methods: A United States online sample of sexually experienced transgender youth ages 13-24 years (N = 1029) in 2018 completed a cross-sectional survey, including questions about sociodemographics, medical gender affirmation, and HIV and STD prevention outcomes (HIV testing, STD testing, pre-exposure prophylaxis [PrEP] awareness, and nonoccupational postexposure prophylaxis [nPEP] awareness). Logistic regression models were fit to assess the association of medical gender affirmation with HIV and STD prevention outcomes. Interaction terms and stratified models assessed differences in the association between medical gender affirmation and outcomes by gender identity. Results: Participants' mean age was 19.1 (standard deviation = 2.7), 45% were transgender female, 29% transgender male, 26% nonbinary, 53% were youth of color, and 19% accessed medical gender affirmation services. Medical gender affirmation was associated with increased odds of STD testing (adjusted odds ratio [aOR] = 1.90; 95% confidence interval [CI] = 1.33-2.73) with no significant interactions by gender identity. Associations between medical gender affirmation and awareness of PrEP and nPEP varied by gender identity. Among transgender male youth, medical gender affirmation was associated with awareness of PrEP (aOR = 2.65; 95% CI = 1.50-4.71) and nPEP (aOR = 2.03; 95% CI = 1.12-3.71). Among nonbinary youth, medical gender affirmation was associated with awareness of PrEP (aOR = 3.47; 95% CI = 1.26-11.27). Conclusion: Medical gender affirmation was associated with uptake and awareness of sexual health services. Bolstering medical gender affirmation for transgender youth may also bolster preventive health services broadly.

      2. Observed face mask use at six universities - United States, September-November 2020external icon
        Barrios LC, Riggs MA, Green RF, Czarnik M, Nett RJ, Staples JE, Welton MD, Muilenburg JL, Zullig KJ, Gibson-Young L, Perkins AV, Prins C, Lauzardo M, Shapiro J, Asimellis G, Kilgore-Bowling G, Ortiz-Jurado K, Gutilla MJ.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 12;70(6):208-211.
        Approximately 41% of adults aged 18-24 years in the United States are enrolled in a college or university (1). Wearing a face mask can reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (2), and many colleges and universities mandate mask use in public locations and outdoors when within six feet of others. Studies based on self-report have described mask use ranging from 69.1% to 86.1% among adults aged 18-29 years (3); however, more objective measures are needed. Direct observation by trained observers is the accepted standard for monitoring behaviors such as hand hygiene (4). In this investigation, direct observation was used to estimate the proportion of persons wearing masks and the proportion of persons wearing masks correctly (i.e., covering the nose and mouth and secured under the chin*) on campus and at nearby off-campus locations at six rural and suburban universities with mask mandates in the southern and western United States. Trained student observers recorded mask use for up to 8 weeks from fixed sites on campus and nearby. Among 17,200 observed persons, 85.5% wore masks, with 89.7% of those persons wearing the mask correctly (overall correct mask use: 76.7%). Among persons observed indoors, 91.7% wore masks correctly. The proportion correctly wearing masks indoors varied by mask type, from 96.8% for N95-type masks and 92.2% for cloth masks to 78.9% for bandanas, scarves, and similar face coverings. Observed indoor mask use was high at these six universities with mask mandates. Colleges and universities can use direct observation findings to tailor training and messaging toward increasing correct mask use.

      3. The relationship between social vulnerability and COVID-19 incidence among Louisiana census tractsexternal icon
        Biggs EN, Maloney PM, Rung AL, Peters ES, Robinson WT.
        Front Public Health. 2020 ;8:617976.
        Objective: To examine the association between the Centers for Disease Control and Prevention (CDC)'s Social Vulnerability Index (SVI) and COVID-19 incidence among Louisiana census tracts. Methods: An ecological study comparing the CDC SVI and census tract-level COVID-19 case counts was conducted. Choropleth maps were used to identify census tracts with high levels of both social vulnerability and COVID-19 incidence. Negative binomial regression with random intercepts was used to compare the relationship between overall CDC SVI percentile and its four sub-themes and COVID-19 incidence, adjusting for population density. Results: In a crude stratified analysis, all four CDC SVI sub-themes were significantly associated with COVID-19 incidence. Census tracts with higher levels of social vulnerability were associated with higher COVID-19 incidence after adjusting for population density (adjusted RR: 1.52, 95% CI: 1.41-1.65). Conclusions: The results of this study indicate that increased social vulnerability is linked with COVID-19 incidence. Additional resources should be allocated to areas of increased social disadvantage to reduce the incidence of COVID-19 in vulnerable populations.

      4. Clinical symptoms among ambulatory patients tested for SARS-CoV-2external icon
        Chung JR, Kim SS, Jackson ML, Jackson LA, Belongia EA, King JP, Zimmerman RK, Nowalk MP, Martin ET, Monto AS, Gaglani M, Smith ME, Patel M, Flannery B.
        Open Forum Infect Dis. 2021 Jan;8(1):ofaa576.
        We compared symptoms and characteristics of 4961 ambulatory patients with and without laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations).

      5. COVID-19 clinical phenotypes: Presentation and temporal progression of disease in a cohort of hospitalized adults in Georgia, United Statesexternal icon
        da Silva JF, Hernandez-Romieu AC, Browning SD, Bruce BB, Natarajan P, Morris SB, Gold JA, Neblett Fanfair R, Rogers-Brown J, Rossow J, Szablewski CM, Oosmanally N, D'Angelo MT, Drenzek C, Murphy DJ, Hollberg J, Blum JM, Jansen R, Wright DW, Sewell W, Owens J, Lefkove B, Brown FW, Burton DC, Uyeki TM, Patel PR, Jackson BR, Wong KK.
        Open Forum Infect Dis. 2021 Jan;8(1):ofaa596.
        BACKGROUND: The epidemiological features and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) have been described; however, the temporal progression and medical complications of disease among hospitalized patients require further study. Detailed descriptions of the natural history of COVID-19 among hospitalized patients are paramount to optimize health care resource utilization, and the detection of different clinical phenotypes may allow tailored clinical management strategies. METHODS: This was a retrospective cohort study of 305 adult patients hospitalized with COVID-19 in 8 academic and community hospitals. Patient characteristics included demographics, comorbidities, medication use, medical complications, intensive care utilization, and longitudinal vital sign and laboratory test values. We examined laboratory and vital sign trends by mortality status and length of stay. To identify clinical phenotypes, we calculated Gower's dissimilarity matrix between each patient's clinical characteristics and clustered similar patients using the partitioning around medoids algorithm. RESULTS: One phenotype of 6 identified was characterized by high mortality (49%), older age, male sex, elevated inflammatory markers, high prevalence of cardiovascular disease, and shock. Patients with this severe phenotype had significantly elevated peak C-reactive protein creatinine, D-dimer, and white blood cell count and lower minimum lymphocyte count compared with other phenotypes (P < .01, all comparisons). CONCLUSIONS: Among a cohort of hospitalized adults, we identified a severe phenotype of COVID-19 based on the characteristics of its clinical course and poor prognosis. These findings need to be validated in other cohorts, as improved understanding of clinical phenotypes and risk factors for their development could help inform prognosis and tailored clinical management for COVID-19.

      6. Mitigating SARS-CoV-2 transmission in Hispanic and Latino communities - Prince William Health District, Virginia, June 2020external icon
        Davlantes E, Tippins A, Espinosa C, Lofgren H, Leonard S, Solis M, Young A, Sockwell D, Ansher A.
        J Racial Ethn Health Disparities. 2021 Feb 4:1-9.
        OBJECTIVES: To identify factors contributing to disproportionate rates of COVID-19 among Hispanic or Latino persons in Prince William Health District, Virginia, and to identify measures to better engage Hispanic and Latino communities in COVID-19 mitigation. METHODS: Data collection proceeded via three methods in June 2020: a quantitative survey of Hispanic or Latino residents, key informant interviews with local leaders familiar with this population, and focus group discussions with Hispanic or Latino community members. RESULTS: Those who worked outside the home, lived in larger households, or lived with someone who had tested positive were more likely to report testing positive for SARS-CoV-2 (unadjusted odds ratios of 2.5, 1.2, and 12.9, respectively). Difficulty implementing COVID-19 prevention practices (reported by 46% of survey respondents), immigration-related fears (repeatedly identified in qualitative data), and limited awareness of local COVID-19 resources (57% of survey respondents spoke little or no English) were identified. Survey respondents also reported declines in their food security (25%) and mental health (25%). CONCLUSIONS: Specific attention to the needs of Hispanic or Latino communities could help reduce the burden of COVID-19. The investigation methods can also be used by other jurisdictions to evaluate the needs of and services provided to diverse underserved populations.

      7. Population viral load, viremia and recent HIV-1 infections: Findings from population-based HIV impact assessments (PHIAs) in Zimbabwe, Malawi, and Zambiaexternal icon
        Farahani M, Radin E, Saito S, Sachathep K, Hladik WA, Voetsch AC, Auld A, Balachandra S, Tippett Barr B, Low A, Smart TF, Musuka G, Jonnalagadda S, Hakim A, Wadonda-Kabondo NW, Jahn A, Mugurungi O, Williams D, Barradas DO, Payne D, Parekh B, Patel H, Wiesner L, Hoos D, Justman J.
        J Acquir Immune Defic Syndr. 2021 Feb 5.
        BACKGROUND: HIV population viral load (PVL) can reflect antiretroviral therapy (ART) program effectiveness and transmission potential in a community. Using nationally representative data from household surveys conducted in Zimbabwe, Malawi, and Zambia in 2015-16, we examined the association between various VL measures and the probability of at least one recent HIV-1 infection in the community. METHODS: We used Limiting-antigen (LAg) Avidity enzyme immunoassay (EIA), VLS (HIV RNA <1000 copies/mL), and ARVs in the blood to identify recent HIV-1 cases. RESULTS: Among 1,510 EAs across the three surveys, 52,036 adults aged 15-59 years resided in 1,363 (90.3%) EAs with at least one HIV-positive adult consenting to interview and blood draw and whose VL was tested. Mean HIV prevalence across these EAs was 13.1% (95% confidence intervals [CI] 12.7-13.5). Mean VLS prevalence across these EAs was 58.7% (95% CI 57.3-60.0).In multivariable analysis, PVL was associated with a recent HIV-1 case in that EA (adjusted odds ratio [AOR]: 1.4, 95% CI 1.2-1.6, p=0.001). VLS prevalence was inversely correlated with recent infections (AOR: 0.3, 95% CI 0.1-0.6, p=0.004). The 90-90-90 indicators, namely, the prevalence of HIV diagnosis, ART coverage, and VLS at the EA level, were inversely correlated with HIV recency at the EA level. CONCLUSION: We found a strong association between PVL and VLS prevalence and recent HIV-1 infection at the EA level across three southern African countries with generalized HIV epidemics. These results suggest that population-based measures of VLS in communities may serve as a proxy for epidemic control.

      8. High prevalence of chlamydia and gonorrhea and the need for sexually transmitted infection testing among men who have sex with men and transgender women in Papua New Guineaexternal icon
        Hakim AJ, Iwamoto C, Badman SG, Willie B, Pekon S, Aeno H, Neo-Boli R, Ase S, Weikum D, Vallely AJ, Kelly-Hanku A.
        Sex Transm Dis. 2021 Feb 1;48(2):109-117.
        BACKGROUND: Papua New Guinea has among the highest prevalence of sexually transmitted infections in the world but no estimates of Chlamydia trachomatis, Neisseria gonorrhoeae, or hepatitis B virus (HBV) are available among men who have sex with men (MSM) or transgender women (TGW). METHODS: We conducted respondent-driven sampling surveys among MSM and TGW in Port Moresby, Lae, and Mt Hagen (2016-2017) to characterize the prevalence of these infections. Eligibility criteria were as follows: aged ≥12 years, born male, could speak English or Tok Pisin, and had oral or anal sex with another person born male in the past 6 months. Participants were surveyed face-to-face and offered testing for anorectal and genital chlamydia and gonorrhea, syphilis, HIV, and HBV. All results are respondent-driven sampling weighted. RESULTS: We enrolled 400 participants in Port Moresby, 352 in Lae, and 111 in Mt Hagen. Chlamydia prevalence rates in the 3 cities regardless of anatomical site were 19.9%, 19.2%, and 24.3%, respectively. Gonorrhea prevalence rates regardless of anatomical site were 10.3%, 9.4%, and 9.6%, respectively. Hepatitis B virus prevalence rates were 11.7%, 13.8%, and 13.6%, respectively. In multivariable analysis, syphilis was associated with having either chlamydia or gonorrhea in Port Moresby (adjusted odds ratio, 4.0; 95% confidence interval, 2.0-7.9) and Lae (adjusted odds ratio, 2.4; 95% confidence interval, 1.2-5.0). CONCLUSIONS: There is a large unmet need among MSM and TGW in Papua New Guinea for chlamydia and gonorrhea detection and treatment. The high prevalence of HBV reinforces the importance of ensuring introduction and scale-up of HBV treatment and immunization. Urgent efforts are needed to introduce laboratory-based diagnosis for chlamydia and gonorrhea to ensure these populations have access to much needed treatment services.

      9. Adverse outcomes in pregnant women hospitalized with respiratory syncytial virus infection: A case seriesexternal icon
        Hause AM, Panagiotakopoulos L, Weintraub ES, Sy LS, Glenn SC, Tseng HF, McNeil MM.
        Clin Infect Dis. 2021 Jan 23;72(1):138-140.
        We identified 10 women hospitalized with respiratory syncytial virus infection during pregnancy. Diagnoses included pneumonia/atelectasis (5), respiratory failure (2), and sepsis (2). Six had obstetrical complications during hospitalization, including 1 induced preterm birth. One required intensive care unit admission and mechanical ventilation. Four infants had complications at birth.

      10. Occupational risk factors for SARS-CoV-2 infection among healthcare personnel: A cross-sectional analysis of subjects enrolled in the COPE Studyexternal icon
        Howard-Anderson J, Adams C, Sherman AC, Dube WC, Smith TC, Edupuganti N, Chea N, Magill SS, Espinoza DO, Zhu Y, Phadke VK, Edupuganti S, Steinberg JP, Lopman BA, Jacob JT, Collins MH, Fridkin SK.
        Infect Control Hosp Epidemiol. 2021 Feb 9:1-20.
        Among 353 healthcare personnel in a longitudinal cohort in four hospitals in Atlanta, GA (May-June 2020), 23 (6.5%) had SARS-CoV-2 antibodies. Spending >50% of a typical shift at bedside (OR 3.4, 95% CI: 1.2-10.5) and Black race (OR 8.4, 95% CI: 2.7-27.4) were associated with SARS-CoV-2 seropositivity.

      11. Decline in COVID-19 hospitalization growth rates associated with statewide mask mandates - 10 states, March-October 2020external icon
        Joo H, Miller GF, Sunshine G, Gakh M, Pike J, Havers FP, Kim L, Weber R, Dugmeoglu S, Watson C, Coronado F.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 12;70(6):212-216.
        SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is transmitted predominantly by respiratory droplets generated when infected persons cough, sneeze, spit, sing, talk, or breathe. CDC recommends community use of face masks to prevent transmission of SARS-CoV-2 (1). As of October 22, 2020, statewide mask mandates were in effect in 33 states and the District of Columbia (2). This study examined whether implementation of statewide mask mandates was associated with COVID-19-associated hospitalization growth rates among different age groups in 10 sites participating in the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) in states that issued statewide mask mandates during March 1-October 17, 2020. Regression analysis demonstrated that weekly hospitalization growth rates declined by 2.9 percentage points (95% confidence interval [CI] = 0.3-5.5) among adults aged 40-64 years during the first 2 weeks after implementing statewide mask mandates. After mask mandates had been implemented for ≥3 weeks, hospitalization growth rates declined by 5.5 percentage points among persons aged 18-39 years (95% CI = 0.6-10.4) and those aged 40-64 years (95% CI = 0.8-10.2). Statewide mask mandates might be associated with reductions in SARS-CoV-2 transmission and might contribute to reductions in COVID-19 hospitalization growth rates, compared with growth rates during <4 weeks before implementation of the mandate and the implementation week. Mask-wearing is a component of a multipronged strategy to decrease exposure to and transmission of SARS-CoV-2 and reduce strain on the health care system, with likely direct effects on COVID-19 morbidity and associated mortality.

      12. Re-emergence of influenza virus circulation during 2020 in parts of tropical Asia: Implications for other countriesexternal icon
        Mott JA, Fry AM, Kondor R, Wentworth DE, Olsen SJ.
        Influenza Other Respir Viruses. 2021 Feb 10.

      13. Antibody responses to two recombinant treponemal antigens (rp17 and TmpA) before and after azithromycin treatment for yaws in Ghana and Papua New Guineaexternal icon
        Parameswaran N, Mitjà O, Bottomley C, Kwakye C, Houinei W, Pillay A, Danavall D, Chi KH, Ballard RC, Solomon AW, Chen CY, Bieb SV, Adu-Sarkodie Y, Mabey DC, Asiedu K, Marks M, Martin D.
        J Clin Microbiol. 2021 Feb 10.
        WHO and its partners aim to interrupt yaws transmission in endemic countries and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical.We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6-15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semi-quantitative bead-based immunoassay.Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold-change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not.Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.

      14. Risk of clinical severity by age and race/ethnicity among adults hospitalized for COVID-19 - United States, March-September 2020external icon
        Pennington AF, Kompaniyets L, Summers AD, Danielson ML, Goodman AB, Chevinsky JR, Preston LE, Schieber LZ, Namulanda G, Courtney J, Strosnider HM, Boehmer TK, Mac Kenzie WR, Baggs J, Gundlapalli AV.
        Open Forum Infect Dis. 2021 Feb;8(2):ofaa638.
        BACKGROUND: Older adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. METHODS: Using data from the Premier Healthcare Database on 181( )813 hospitalized adults diagnosed with COVID-19 during March-September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity. RESULTS: Overall, 84( )497 (47%) patients were admitted to the ICU, 29( )078 (16%) received IMV, and 27( )864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92-0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09-1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09-1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06-1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups. CONCLUSIONS: These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes.

      15. Modeling effectiveness of testing strategies to prevent COVID-19 in nursing homes -United States, 2020external icon
        See I, Paul P, Slayton RB, Steele MK, Stuckey MJ, Duca L, Srinivasan A, Stone N, Jernigan JA, Reddy SC.
        Clin Infect Dis. 2021 Feb 10.
        BACKGROUND: SARS-CoV-2 outbreaks in nursing homes can be large with high case fatality. Identifying asymptomatic individuals early through serial testing is recommended to control COVID-19 in nursing homes, both in response to an outbreak ("outbreak testing" of residents and healthcare personnel) and in facilities without outbreaks ("non-outbreak testing" of healthcare personnel). The effectiveness of outbreak testing and isolation with or without non-outbreak testing was evaluated. METHODS: Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., "effectiveness") through either outbreak testing alone or outbreak plus non-outbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated. RESULTS: Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak testing were mostly negated if accompanied by decreases in infection control practice. CONCLUSIONS: When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.

      16. The persistence of underreporting of hepatitis C as an underlying or contributing cause of death, 2011-2017external icon
        Spradling PR, Zhong Y, Moorman AC, Rupp LB, Lu M, Teshale EH, Schmidt MA, Daida YG, Boscarino JA, Gordon SC.
        Clin Infect Dis. 2021 Feb 9.
        Using electronic health records, we found that hepatitis C reporting on death certificates of 2,901 HCV-infected decedents from four U.S. healthcare organizations during 2011-2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the U.S. HCV mortality burden.

      17. Signs, symptoms, and comorbidities associated with poor outcomes among residents of a skilled nursing facility with SARS-CoV-2 infection - King County, Washingtonexternal icon
        Tobolowsky FA, Bardossy AC, Currie DW, Schwartz NG, Zacks RL, Chow EJ, Dyal JW, Ali H, Kay M, Duchin JS, Brostrom-Smith C, Clark S, Sykes K, Jernigan JA, Honein MA, Clark TA, Stone ND, Reddy SC, Rao AK.
        J Am Med Dir Assoc. 2021 Jan 28.
        BACKGROUND: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. METHODS: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. RESULTS: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. CONCLUSIONS AND IMPLICATIONS: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor.

      18. Prevalence of urogenital Mycoplasma genitalium infection, United States, 2017-2018external icon
        Torrone E, Kruszon-Moran D, Philips C, Morris M, Bowden K, Papp J, Bachmann LH, Weinstock H, Kersh EN.
        Sex Transm Dis. 2021 Feb 9.
        During the 2017-2018 National Health and Nutrition Examination Survey, urine samples from participants aged 14-59 years were tested for Mycoplasma genitalium infection. Overall prevalence was 1.7% (95% CI: 1.1%, 2.7%). Prevalence was similar between males (1.8%, 95% CI: 0.9%, 3.1%) and females (1.7%, 95% CI: 0.8%, 3.0%).

      19. Social distancing policies in 22 African countries during the COVID-19 pandemic: a desk reviewexternal icon
        Verani A, Clodfelter C, Menon AN, Chevinsky J, Victory K, Hakim A.
        Pan Afr Med J. 2020 ;37(Suppl 1):46.
        INTRODUCTION: on January 30, 2020, the World Health Organization declared the novel coronavirus outbreak a Public Health Emergency of International Concern. As of October 5, 2020, there were over 34.8 million reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and more than 1 million reported deaths from coronavirus disease 2019 (COVID-19), globally. Non-pharmaceutical interventions, such as social distancing policies, hand hygiene, and mask use, are key public health measures to control COVID-19. In response to, or in some cases even before, the first wave of SARS-CoV-2 infections were reported in their countries, policy makers across Africa issued various social distancing policies. METHODS: we describe social distancing policies issued from March 1 to April 24, 2020 in 22 Anglophone countries of sub-Saharan Africa. We reviewed policies identified online. RESULTS: though all 22 countries closed schools and banned gatherings, they took a variety of approaches to sizes of gatherings banned and to stay-at-home orders, with 13 countries issuing national stay-at-home orders, four issuing subnational stay-at-home orders, and five not issuing stay-at-home orders. Enforcement provisions varied by country, as did funeral and health care exceptions. CONCLUSION: movement restrictions, business restrictions, and school closures can have substantial negative impacts on economies, education, nutrition, and routine health care. Yet easing or lifting of COVID-19 social distancing policies can lead to increased transmission. Our review documents a wide variety of policy alternatives used in Africa and can inform future adjustments as countries ease, lift, and reapply measures in response to their evolving epidemics.

      20. Optimising pyrazinamide for the treatment of tuberculosisexternal icon
        Zhang N, Savic RM, Boeree MJ, Peloquin C, Weiner M, Heinrich N, Bliven-Sizemore E, Phillips PP, Hoelscher M, Whitworth W, Morlock G, Posey J, Stout JE, Mac Kenzie W, Aarnoutse R, Dooley KE.
        Eur Respir J. 2021 Feb 4.
        Pyrazinamide is a potent sterilising agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimises efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further.Pharmacokinetic data, sputum culture, and safety laboratory results were compiled from TBTC Studies 27 and 28 and PanACEA MAMS-TB, multi-center Phase 2 trials in which participants received rifampicin (range 10-35 mg·kg(-1)), pyrazinamide (range 20-30 mg·kg(-1)), plus two companion drugs. Pyrazinamide pharmacokinetic-pharmacodynamic (PK/PD) and PK-toxicity analyses were performed.In TBTC studies (n=77), higher pyrazinamide maximum concentration (Cmax) was associated with shorter time to culture conversion (TTCC) and higher probability of two-month culture conversion (p-value<0.001). Parametric survival analyses showed that relationships varied geographically, with steeper PK-PD relationships seen among non-African than African participants. In PanACEA MAMS-TB (n=363), TTCC decreased as pyrazinamide Cmax increased and varied by rifampicin Cmax (p-value<0.01). Modeling and simulation suggested that very high doses of pyrazinamide (>4500 mg) or increasing both pyrazinamide and rifampicin would be required to reach targets associated with treatment shortening. Combining all trials, liver toxicity was rare (3.9% with Grade 3 or higher liver function tests, LFT), and no relationship was seen between pyrazinamide Cmax and LFT levels.Pyrazinamide's microbiologic efficacy increases with increasing drug concentrations. Optimising pyrazinamide alone, though, is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel.

    • Disaster Control and Emergency Services
      1. Refugee settlements and cholera risks in Uganda, 2016-2019external icon
        Bwire G, Orach CG, Aceng FL, Arianitwe SE, Matseketse D, Tumusherure E, Issa M, Muruta A, Merrill RD, Debes A, Ali M, Sack DA.
        Am J Trop Med Hyg. 2021 Feb 8.
        During 2016 to 2019, cholera outbreaks were reported commonly to the Ministry of Health from refugee settlements. To further understand the risks cholera posed to refugees, a review of surveillance data on cholera in Uganda for the period 2016-2019 was carried out. During this 4-year period, there were seven such outbreaks with 1,495 cases and 30 deaths in five refugee settlements and one refugee reception center. Most deaths occurred early in the outbreak, often in the settlements or before arrival at a treatment center rather than after arrival at a treatment center. During the different years, these outbreaks occurred during different times of the year but simultaneously in settlements that were geographically separated and affected all ages and genders. Some outbreaks spread to the local populations within Uganda. Cholera control prevention measures are currently being implemented; however, additional measures are needed to reduce the risk of cholera among refugees including oral cholera vaccination and a water, sanitation and hygiene package during the refugee registration process. A standardized protocol is needed to quickly conduct case-control studies to generate information to guide future cholera outbreak prevention in refugees and the host population.

      2. Impact of hurricanes on children with asthma: A systematic literature reviewexternal icon
        Cowan KN, Pennington AF, Gregory T, Hsu J.
        Disaster Med Public Health Prep. 2021 Feb 9:1-6.
        Following hurricanes, there can be increases in exacerbations of chronic diseases, such as asthma. Asthma is common among children, and many asthma exacerbations can be prevented. This systematic literature review assessed literature describing the impact of hurricanes on children with asthma in the United States. Medline, Embase, Global Health, PubMed, and Scopus databases were searched for peer-reviewed, English-language articles published January 1990 to June 2019 that described the effect of a hurricane on children with asthma. This search identified 212 articles; 8 met inclusion criteria. All 8 were related to Hurricane Katrina, but research questions and study design varied. Articles included information on asthma after hurricanes from cross-sectional surveys, retrospective chart review, and objective clinical testing. Four articles described discontinuity in health insurance, asthma-related health care, or asthma medication use; and 3 articles examined the relationship between mold exposure and asthma symptoms and reported varying results. The eighth study quantified the burden of asthma among people visiting mobile medical units but did not describe factors associated with asthma symptoms. These results highlight opportunities for future research (eg, on more recent hurricanes) and disaster preparedness planning (eg, strategies to prevent health-care discontinuity among children with asthma).

      3. Structure, function and performance of Early Warning Alert and Response Network (EWARN) in emergencies in the Eastern Mediterranean Regionexternal icon
        Mala P, Abubakar A, Takeuchi A, Buliva E, Husain F, Malik MR, Tayyab M, Elnoserry S.
        Int J Infect Dis. 2021 Feb 5.
        INTRODUCTION: The Eastern Mediterranean Region (EMR) has experienced several protracted humanitarian crises. The affected population are served by eight EWARN systems for outbreak detection and response. Our aim was to compare structure, function, and performance of the systems, adherence to current guidance, and note emerging lessons. METHODS: This study included a review of published and unpublished literature, a structured survey, and interviews. RESULTS: Findings showed all systems adhered to basic EWARN structure. Four of eight systems had electronic platforms while one was implementing. Regarding key EWARN function of outbreak detection, out of the 35 health conditions, 26 were communicable diseases and nine were non-communicable; only two systems focused on epidemic-prone diseases. Half the systems achieved ≥60% population coverage, five achieved ≥80% reporting timeliness, six achieved ≥80% reporting completeness, and seven achieved verification of ≥80% of alerts of suspected outbreaks. CONCLUSION: Findings showed that the systems followed EWARN structure while increasing adoption of electronic platforms. Performance, including timeliness and completeness of reporting, and timely verification of alerts, were optimal for most of the systems. However, population coverage was low for most of the systems, and EWARN's primary focus of outbreak detection was being undermined by increasing number of non-epidemic diseases.

    • Disease Reservoirs and Vectors
      1. Sylvatic populations of Triatoma infestans represent a challenge to Chagas disease control as they are not targeted by vector control activities and may play a key role in post-spraying house re-infestation. Understanding sylvatic foci distribution and gene flow between sylvatic and domestic populations is crucial to optimize vector control interventions and elucidate the development and spread of insecticide resistance. Herein, the genetic profiles of five Andean T. infestans populations from Bolivia with distinct insecticide susceptibility profiles were compared. Multilocus genotypes based on eight microsatellites and the DNA sequence of a fragment of the cytochrome B (cytB) gene were obtained for 92 individuals. CytB haplotypes were analyzed with previously reported Bolivian T. infestans haplotypes to evaluate putative historical gene flow among populations. Each specimen was also screened for two nucleotide mutations in the sodium channel gene (kdr), related to pyrethroid resistance (L1014 and L9251). Significant genetic differentiation was observed among all populations, although individuals of admixed origin were detected in four of them. Notably, the genetic profiles of adjacent domestic and sylvatic populations of Mataral, characterized by higher levels of insecticide resistance, support their common ancestry. Only one sylvatic individual from Mataral carried the kdr mutation L1014, suggesting that this mechanism is unlikely to cause the altered insecticide susceptibility observed in these populations. However, as the resistance mutation is present in the area, it has the potential to be selected under insecticidal pressure. Genetic comparisons of these populations suggest that insecticide resistance is likely conferred by ancient trait(s) in T. infestans sylvatic populations, which are capable of invading domiciles. These results emphasize the need for stronger entomological surveillance in the region, including early detection of house invasion, particularly post-spraying, monitoring for resistance to pyrethroids and the design of integrative control actions that consider sylvatic foci around domestic settings and their dispersion dynamics.

      2. Oropouche virus (OROV), a vector-borne Orthobunyavirus circulating in South and Central America, causes a febrile illness with high rates of morbidity but with no documented fatalities. Oropouche virus is transmitted by numerous vectors, including multiple genera of mosquitoes and Culicoides biting midges in South America. This study investigated the vector competence of three North American vectors, Culex tarsalis, Culex quinquefasciatus, and Culicoides sonorensis, for OROV. Cohorts of each species were fed an infectious blood meal containing 6.5 log(10) PFU/mL OROV and incubated for 10 or 14 days. Culex tarsalis demonstrated infection (3.13%) but not dissemination or transmission potential at 10 days post infection (DPI). At 10 and 14 DPI, Cx. quinquefasciatus demonstrated 9.71% and 19.3% infection, 2.91% and 1.23% dissemination, and 0.97% and 0.82% transmission potential, respectively. Culicoides sonorensis demonstrated 86.63% infection, 83.14% dissemination, and 19.77% transmission potential at 14 DPI. Based on these data, Cx. tarsalis is unlikely to be a competent vector for OROV. Culex quinquefasciatus demonstrated infection, dissemination, and transmission potential, although at relatively low rates. Culicoides sonorensis demonstrated high infection and dissemination but may have a salivary gland barrier to the virus. These data have implications for the spread of OROV in the event of a North American introduction.

      3. Rift Valley fever and Crimean-Congo hemorrhagic fever viruses in ruminants, Jordanexternal icon
        Obaidat MM, Graziano JC, Morales-Betoulle M, Brown SM, Chiang CF, Klena JD.
        Emerg Infect Dis. 2021 ;27(2):653-655.
        The epidemiology of Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) in Jordan is unknown. Our investigation showed 3% of 989 tested dairy cattle, sheep, and goats were RVFV seropositive and 14% were CCHFV seropositive. Ongoing surveillance is needed to assess risk to humans and protect public health.

      4. Western Kenyan Anopheles gambiae showing intense permethrin resistance harbour distinct microbiotaexternal icon
        Omoke D, Kipsum M, Otieno S, Esalimba E, Sheth M, Lenhart A, Njeru EM, Ochomo E, Dada N.
        Malar J. 2021 Feb 8;20(1):77.
        BACKGROUND: Insecticide resistance poses a growing challenge to malaria vector control in Kenya and around the world. Following evidence of associations between the mosquito microbiota and insecticide resistance, the microbiota of Anopheles gambiae sensu stricto (s.s.) from Tulukuyi village, Bungoma, Kenya, with differing permethrin resistance profiles were comparatively characterized. METHODS: Using the CDC bottle bioassay, 133 2-3 day-old, virgin, non-blood fed female F(1) progeny of field-caught An. gambiae s.s. were exposed to five times (107.5 µg/ml) the discriminating dose of permethrin. Post bioassay, 50 resistant and 50 susceptible mosquitoes were subsequently screened for kdr East and West mutations, and individually processed for microbial analysis using high throughput sequencing targeting the universal bacterial and archaeal 16S rRNA gene. RESULTS: 47 % of the samples tested (n = 133) were resistant, and of the 100 selected for further processing, 99 % were positive for kdr East and 1 % for kdr West. Overall, 84 bacterial taxa were detected across all mosquito samples, with 36 of these shared between resistant and susceptible mosquitoes. A total of 20 bacterial taxa were unique to the resistant mosquitoes and 28 were unique to the susceptible mosquitoes. There were significant differences in bacterial composition between resistant and susceptible individuals (PERMANOVA, pseudo-F = 2.33, P = 0.001), with presence of Sphingobacterium, Lysinibacillus and Streptococcus (all known pyrethroid-degrading taxa), and the radiotolerant Rubrobacter, being significantly associated with resistant mosquitoes. On the other hand, the presence of Myxococcus, was significantly associated with susceptible mosquitoes. CONCLUSIONS: This is the first report of distinct microbiota in An. gambiae s.s. associated with intense pyrethroid resistance. The findings highlight differentially abundant bacterial taxa between resistant and susceptible mosquitoes, and further suggest a microbe-mediated mechanism of insecticide resistance in mosquitoes. These results also indicate fixation of the kdr East mutation in this mosquito population, precluding further analysis of its associations with the mosquito microbiota, but presenting the hypothesis that any microbe-mediated mechanism of insecticide resistance would be likely of a metabolic nature. Overall, this study lays initial groundwork for understanding microbe-mediated mechanisms of insecticide resistance in African mosquito vectors of malaria, and potentially identifying novel microbial markers of insecticide resistance that could supplement existing vector surveillance tools.

    • Environmental Health
      1. Prenatal exposure to poly- and perfluoroalkyl substances (PFAS) and neurobehavior in US children through 8 years of age: the HOME Studyexternal icon
        Vuong AM, Webster GM, Yolton K, Calafat AM, Muckle G, Lanphear BP, Chen A.
        Environ Res. 2021 Feb 2:110825.
        BACKGROUND: Studies of prenatal poly- and perfluoroalkyl substances (PFAS) and attention deficit hyperactivity disorder (ADHD)-related behaviors in children are inconsistent. OBJECTIVES: To examine associations between maternal serum PFAS concentrations and child behavior in 241 mother-child dyads within the Health Outcomes and Measures of the Environment (HOME) Study. METHODS: We quantified perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) in maternal serum collected during pregnancy or at delivery. We evaluated a total of 17 outcomes of child behavior using the Behavioral Assessment System for Children-2 (BASC-2) at 5 and 8 years (n=240) and ADHD diagnostic symptoms and criteria with the Diagnostic Interview Schedule for Children-Young Child (DISC-YC) at 5 years (n=190). We used linear mixed models and logistic regression with generalized estimating equations to assess associations between PFAS and continuous or dichotomous "at risk" BASC-2 scores; negative binomial regression to calculate incident rate ratios for counts of ADHD symptoms; and Poisson regression with robust standard errors to calculate relative risks of meeting ADHD diagnostic criteria. RESULTS: Each ln-unit increase in PFOS, PFHxS, PFNA was associated with higher BASC-2 scores and increased odds of "at-risk" scores for externalizing behaviors, including hyperactivity (PFOS: odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2, 5.9; PFHxS: OR 2.5, 95% CI 1.5, 4.3; PFNA: OR 3.2, 95% CI 1.3, 8.0). PFHxS was also associated with internalizing problems (OR 2.0, 95% CI 1.1, 3.4) and somatization (OR 2.2, 95% CI 1.2, 4.0). PFOS and PFNA were significantly associated with 50-80% more DISC-YC symptoms and diagnostic criteria related to hyperactive-impulsive type and combined-type ADHD. Prenatal PFNA was associated with increased risk of any-type ADHD. CONCLUSIONS: Prenatal PFOS and PFNA were consistently associated with measures related to hyperactive-impulsive type ADHD across two validated assessment instruments. PFHxS was associated with increased problems with both externalizing and internalizing behaviors. No associations were noted between PFOA and child neurobehavior.

    • Epidemiology and Surveillance
      1. INTRODUCTION: Pressure ulcer indicators are among the most frequently used performance measures in long-term care settings. However, measurement systems vary and there is limited knowledge about the international comparability of different measurement systems. The aim of this analysis was to identify possible avenues for international comparisons of data on pressure ulcer prevalence among residents of long-term care facilities. MATERIAL AND METHODS: A descriptive analysis of the four point prevalence measurement systems programs used in 28 countries on three continents was performed. The criteria for the description and analysis were based on the scientific literature on criteria for indicator selection, on issues in international comparisons of data and on specific challenges of pressure ulcer measurements. RESULTS: The four measurement systems use a prevalence measure based on very similar numerator and denominator definitions. All four measurement systems also collect data on patient mobility. They differ in the pressure ulcer classifications used and the requirements for a head-to-toe resident examination. The regional or country representativeness of long-term care facilities also varies among the four measurement systems. CONCLUSIONS: Methodological differences among the point prevalence measurement systems are an important barrier to reliable comparisons of pressure ulcer prevalence data. The alignment of the methodologies may be improved by implementing changes to the study protocols, such as aligning the classification of pressure ulcers and requirements for a head-to-toe resident skin assessment. The effort required for each change varies. All these elements need to be considered by any initiative to facilitate international comparison and learning.

    • Genetics and Genomics
      1. Genomic diversity of Burkholderia pseudomallei isolates, Colombiaexternal icon
        Duarte C, Montufar F, Moreno J, Sánchez D, Rodríguez JY, Torres AG, Morales S, Bautista A, Huertas MG, Myers JN, Gulvik CA, Elrod MG, Blaney DD, Gee JE.
        Emerg Infect Dis. 2021 Feb;27(2):655-658.
        We report an analysis of the genomic diversity of isolates of Burkholderia pseudomallei, the cause of melioidosis, recovered in Colombia from routine surveillance during 2016-2017. B. pseudomallei appears genetically diverse, suggesting it is well established and has spread across the region.

      2. Evaluation of phylogenetic methods for inferring the direction of human immunodeficiency virus (HIV) transmission: HIV Prevention Trials Network (HPTN) 052external icon
        Zhang Y, Wymant C, Laeyendecker O, Grabowski MK, Hall M, Hudelson S, Piwowar-Manning E, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Mills LA, Santos BR, Grinsztejn B, Pilotto JH, Chariyalertsak S, Makhema J, Chen YQ, Cohen MS, Fraser C, Eshleman SH.
        Clin Infect Dis. 2021 Jan 23;72(1):30-37.
        BACKGROUND: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. METHODS: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). RESULTS: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. CONCLUSIONS: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

    • Health Disparities
      1. OBJECTIVE: HIV disproportionately affects Hispanic/Latino people in the United States, and factors other than individual attributes may be contributing to these differences. We examined differences in the distribution of HIV diagnosis and social determinants of health (SDH) among US-born and non-US-born Hispanic/Latino adults in the United States and Puerto Rico. METHODS: We used data reported to the Centers for Disease Control and Prevention's National HIV Surveillance System (NHSS) to determine US census tract-level HIV diagnosis rates and percentages among US-born and non-US-born Hispanic/Latino adults aged ≥18 for 2017. We merged data from the US Census Bureau's American Community Survey with NHSS data to examine regional differences in federal poverty level, education, median household income, employment, and health insurance coverage among 8648 US-born (n = 3328) and non-US-born (n = 5320) Hispanic/Latino adults. RESULTS: A comparison of US-born and non-US-born men by region showed similar distributions of HIV diagnoses. The largest percentages occurred in census tracts where ≥19% of residents lived below the federal poverty level, ≥18% did not finish high school, the median household income was <$40 000 per year, ≥6% were unemployed, and ≥16% did not have health insurance. A comparison of US-born and non-US-born women by region showed similar distributions. CONCLUSION: The findings of higher numbers of HIV diagnoses among non-US-born Hispanic/Latino adults than among US-born Hispanic/Latino adults, regional similarities in patterns of SDH and HIV percentages and rates, and Hispanic/Latino adults faring poorly in each SDH category are important for understanding SDH barriers that may be affecting Hispanic/Latino adults with HIV in the United States.

    • Health Economics
      1. OBJECTIVE: This is a critical review of published economic analyses on congenital cytomegalovirus infection and strategies for its detection and prevention. FINDINGS: The review identified four cost-of-illness studies and nine cost-effectiveness analyses: three of vaccination of young women, two of prenatal screening, and four of newborn screening. All reported either large economic costs or favorable cost-effectiveness of interventions. However, sensitivity analyses did not address some of the most critical assumptions. CONCLUSIONS: Reviewed economic analyses overattributed certain adverse long-term outcomes to congenital cytomegalovirus infection, while other long-term costs were not included. Overall, limited conceptual frameworks, unrepresentative data sources, and unsupported or inadequately documented assumptions regarding outcomes and costs hinder the ability of policymakers to draw conclusions. A major challenge is the limited information on long-term outcomes and costs for representative cohorts of individuals with congenital cytomegalovirus, which further research could helpfully address.

      2. OBJECTIVE: To estimate trends in total payment and patients' out-of-pocket (OOP) payments of noninsulin glucose-lowering drugs by class from 2005 to 2018. RESEARCH DESIGN AND METHODS: We analyzed data for 53 million prescriptions from adults aged >18 years with type 2 diabetes under fee-for-service plans from the 2005-2018 IBM MarketScan Commercial Databases. The total payment was measured as the amount that the pharmacy received, and the OOP payment was the sum of copay, coinsurance, and deductible paid by the beneficiaries. We applied a joinpoint regression to evaluate nonlinear trends in cost between 2005 and 2018. We further conducted a decomposition analysis to explore the drivers for total payment change. RESULTS: Total annual payments for older drug classes, including metformin, sulfonylurea, meglitinide, α-glucosidase inhibitors, and thiazolidinedione, have declined during 2005-2018, ranging from -$271 (-53.8%) (USD) for metformin to -$2,406 (-92.2%) for thiazolidinedione. OOP payments for these drug classes also reduced. In the same period, the total annual payments for the newer drug classes, including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors, have increased by $2,181 (88.4%), $3,721 (77.6%), and $1,374 (37.0%), respectively. OOP payment for these newer classes remained relatively unchanged. Our study findings indicate that switching toward the newer classes for noninsulin glucose-lowering drugs was the main driver that explained the total payment increase. CONCLUSIONS: Average annual payments and OOP payment for noninsulin glucose-lowering drugs have increased significantly from 2005 to 2018. The uptake of newer drug classes was the main driver.

      3. Preterm birth lifetime costs in the United States in 2016: An updateexternal icon
        Waitzman NJ, Jalali A, Grosse SD.
        Semin Perinatol. 2021 Jan 24:151390.
        The societal cost of preterm birth indicates potential economic gains from interventions that reduce the incidence of preterm birth. Changes in the epidemiology of preterm birth and healthcare costs require periodic updates to cost estimates. Previously reported incremental cost estimates for the United States in 2004 were updated. The discounted present value of the excess cost associated with prematurity for the 2016 US birth cohort was estimated to be $25.2 billion: $17.1 billion for medical care of persons born preterm, $2.0 billion for delivery care, $1.3 billion for early intervention and special education, and $4.8 billion in lost productivity due to associated disabilities in adults. The nominal and inflation-adjusted incremental costs per preterm birth increased by 26% and 4%, respectively, during 2004-2016. The aggregate cost decreased by 4%, associated with declines in overall births and the preterm birth rate and changes in the distribution by gestational age.

    • Healthcare Associated Infections

    • Immunity and Immunization
      1. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccineexternal icon
        Bastard P, Michailidis E, Hoffmann HH, Chbihi M, Le Voyer T, Rosain J, Philippot Q, Seeleuthner Y, Gervais A, Materna M, de Oliveira PM, Maia ML, Dinis Ano Bom AP, Azamor T, Araújo da Conceição D, Goudouris E, Homma A, Slesak G, Schäfer J, Pulendran B, Miller JD, Huits R, Yang R, Rosen LB, Bizien L, Lorenzo L, Chrabieh M, Erazo LV, Rozenberg F, Jeljeli MM, Béziat V, Holland SM, Cobat A, Notarangelo LD, Su HC, Ahmed R, Puel A, Zhang SY, Abel L, Seligman SJ, Zhang Q, MacDonald MR, Jouanguy E, Rice CM, Casanova JL.
        J Exp Med. 2021 Apr 5;218(4).
        Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.

      2. At its October 2020 meeting, the Advisory Committee on Immunization Practices (ACIP)* approved the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2021. After the Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine by the Food and Drug Administration, ACIP issued an interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years at its December 12, 2020, emergency meeting (1). In addition, ACIP approved an amendment to include COVID-19 vaccine recommendations in the child and adolescent and adult immunization schedules. After Emergency Use Authorization of Moderna COVID-19 vaccine by the Food and Drug Administration, ACIP issued an interim recommendation for use of Moderna COVID-19 vaccine in persons aged ≥18 years at its December 19, 2020, emergency meeting (2).

      3. Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipientsexternal icon
        Hirzel C, L'Huillier AG, Ferreira VH, Marinelli T, Ku T, Ierullo M, Miao C, Schmid DS, Juvet S, Humar A, Kumar D.
        Am J Transplant. 2021 Feb 10.
        Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n=43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p<0.0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p<0.0001). gE-specific polyfunctional CD4+ T-cell frequencies (n=38) also increased from baseline (median 85 per 10(6) CD4+ T-cells; IQR: 46-180) to the first (median 128 per 10(6) CD4+ T-cells; IQR: 82-353; p=0.023) and after the second dose (median 361 per 10(6) CD4+ T-cells; IQR: 146-848; p<0.0001). Tenderness (83.0%; 95%CI:69.2-92.4%) and redness (31.9%; 95%CI:19.1-47.1%) at injection site were common. One rejection episode within three weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.

      4. COVID-19 vaccination intent, perceptions, and reasons for not vaccinating among groups prioritized for early vaccination - United States, September and December 2020external icon
        Nguyen KH, Srivastav A, Razzaghi H, Williams W, Lindley MC, Jorgensen C, Abad N, Singleton JA.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 12;70(6):217-222.
        As of February 8, 2021, 59.3 million doses of vaccines to prevent coronavirus disease 2019 (COVID-19) had been distributed in the United States, and 31.6 million persons had received at least 1 dose of the COVID-19 vaccine (1). However, national polls conducted before vaccine distribution began suggested that many persons were hesitant to receive COVID-19 vaccination (2). To examine perceptions toward COVID-19 vaccine and intentions to be vaccinated, in September and December 2020, CDC conducted household panel surveys among a representative sample of U.S. adults. From September to December, vaccination intent (defined as being absolutely certain or very likely to be vaccinated) increased overall (from 39.4% to 49.1%); the largest increase occurred among adults aged ≥65 years. If defined as being absolutely certain, very likely, or somewhat likely to be vaccinated, vaccination intent increased overall from September (61.9%) to December (68.0%). Vaccination nonintent (defined as not intending to receive a COVID-19 vaccination) decreased among all adults (from 38.1% to 32.1%) and among most sociodemographic groups. Younger adults, women, non-Hispanic Black (Black) persons, adults living in nonmetropolitan areas, and adults with lower educational attainment, with lower income, and without health insurance were most likely to report lack of intent to receive COVID-19 vaccine. Intent to receive COVID-19 vaccine increased among adults aged ≥65 years by 17.1 percentage points (from 49.1% to 66.2%), among essential workers by 8.8 points (from 37.1% to 45.9%), and among adults aged 18-64 years with underlying medical conditions by 5.3 points (from 36.5% to 41.8%). Although confidence in COVID-19 vaccines increased during September-December 2020 in the United States, additional efforts to tailor messages and implement strategies to further increase the public's confidence, overall and within specific subpopulations, are needed. Ensuring high and equitable vaccination coverage across all populations is important to prevent the spread of COVID-19 and mitigate the impact of the pandemic.

      5. Randomized trial of a vaccine regimen to prevent chronic HCV infectionexternal icon
        Page K, Melia MT, Veenhuis RT, Winter M, Rousseau KE, Massaccesi G, Osburn WO, Forman M, Thomas E, Thornton K, Wagner K, Vassilev V, Lin L, Lum PJ, Giudice LC, Stein E, Asher A, Chang S, Gorman R, Ghany MG, Liang TJ, Wierzbicki MR, Scarselli E, Nicosia A, Folgori A, Capone S, Cox AL.
        N Engl J Med. 2021 Feb 11;384(6):541-549.
        BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10(3) IU per milliliter and 1804.93×10(3) IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; number, NCT01436357.).

      6. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2021external icon
        Wodi AP, Ault K, Hunter P, McNally V, Szilagyi PG, Bernstein H.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 12;70(6):189-192.
        At its October 2020 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the 2021 Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger. After Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine by the Food and Drug Administration (FDA), ACIP issued an interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years at its December 12, 2020, meeting (1). In addition, ACIP approved an amendment to include COVID-19 vaccine recommendations in the child and adolescent immunization schedule. After Emergency Use Authorization of Moderna COVID-19 vaccine by FDA, ACIP issued an interim recommendation for use of Moderna COVID-19 vaccine in persons aged ≥18 years at its December 19, 2020, emergency meeting (2).

    • Informatics
      1. Forecasting influenza activity using machine-learned mobility mapexternal icon
        Venkatramanan S, Sadilek A, Fadikar A, Barrett CL, Biggerstaff M, Chen J, Dotiwalla X, Eastham P, Gipson B, Higdon D, Kucuktunc O, Lieber A, Lewis BL, Reynolds Z, Vullikanti AK, Wang L, Marathe M.
        Nat Commun. 2021 Feb 9;12(1):726.
        Human mobility is a primary driver of infectious disease spread. However, existing data is limited in availability, coverage, granularity, and timeliness. Data-driven forecasts of disease dynamics are crucial for decision-making by health officials and private citizens alike. In this work, we focus on a machine-learned anonymized mobility map (hereon referred to as AMM) aggregated over hundreds of millions of smartphones and evaluate its utility in forecasting epidemics. We factor AMM into a metapopulation model to retrospectively forecast influenza in the USA and Australia. We show that the AMM model performs on-par with those based on commuter surveys, which are sparsely available and expensive. We also compare it with gravity and radiation based models of mobility, and find that the radiation model's performance is quite similar to AMM and commuter flows. Additionally, we demonstrate our model's ability to predict disease spread even across state boundaries. Our work contributes towards developing timely infectious disease forecasting at a global scale using human mobility datasets expanding their applications in the area of infectious disease epidemiology.

    • Injury and Violence
      1. Perpetration of violence by female sex workers in Papua New Guinea: 'We will crush their bones'external icon
        Kelly-Hanku A, Worth H, Redman-Maclaren M, Nosi S, Boli-Neo R, Ase S, Hou P, Aeno H, Kupul M, Amos A, Badman SG, Vallely AJ, Hakim AJ.
        Br J Criminol. 2021 ;61(1):104-122.
        There is a small but important body of literature on female sex workers' (FSWs) violence towards others, but little of that focused on low- and middle-income countries. Drawn from a larger biobehavioural study of FSWs in three cities in Papua New Guinea, we analyse the interviews from 19 FSWs who reported having perpetrated physical violence towards four major groups: (1) ex-husbands; (2) clients; (3) other sex workers and (4) other people (mainly women). Our study demonstrates that FSWs' use of violence arises from a complex set of social, material and gendered circumstances and cannot be addressed in isolation from other aspects of their lives.

      2. BACKGROUND: There is evidence to suggest that traumatic brain injuries (TBI) are increasing in the United States. It is important to examine predictors of TBI outcomes to formulate better prevention and care strategies. RESEARCH DESIGN: National Trauma Data Bank (NTDB) data from 2016 were used to report the percentage of TBI by age, sex, race/ethnicity, health insurance status, intent/mechanism of injury, Glasgow Coma Scale (GCS), disposition at emergency department, and trauma center level. Logistic regression models were run to estimate the adjusted odds ratios of patient and facility characteristics on length of hospital stay and in-hospital mortality (analyzed in 2020). RESULTS: There were 236,873 patients with TBI in the NTDB in 2016. Most patients with a TBI were male, non-Hispanic white, and had sustained a TBI due to an unintentional injury. After adjusting for other factors, individuals age 0-17, those who self-pay, and those with intentional injuries had increased odds of a shorter hospital stay. Older individuals, non-Hispanic black or Hispanic patients, those who had sustained an intentional injury, and those who were not seen in a Level I trauma center had higher odds of mortality following their TBI. CONCLUSIONS: Public health professionals' promotion of fall and other TBI prevention efforts and the development of strategies to improve access to Level I trauma centers, may decrease adverse TBI health outcomes. This may be especially important for older adults and other vulnerable populations.

      3. Pediatric sports-related concussion: An approach to careexternal icon
        Podolak OE, Arbogast KB, Master CL, Sleet D, Grady MF.
        Am J Lifestyle Med. 2021 .
        Sports-related concussion (SRC) is a common sports injury in children and adolescents. With the vast amount of youth sports participation, an increase in awareness of concussion and evidence that the injury can lead to consequences for school, sports and overall quality of life, it has become increasingly important to properly diagnose and manage concussion. SRC in the student athlete is a unique and complex injury, and it is important to highlight the differences in the management of child and adolescent concussion compared with adults. This review focuses on the importance of developing a multimodal systematic approach to diagnosing and managing pediatric sports-related concussion, from the sidelines through recovery.

    • Laboratory Sciences
      1. Haematological reference intervals for healthy adults in Bamenda, Cameroonexternal icon
        Fondoh VN, Fondoh RM, Awasom CN, Edith PL, Ntungwen WA, Roland B, Enow-Tanjong R, Njukeng P, Shang J, Egbengu EP, Maruta T, Etheline A, Leke R, Leo A, Nsame D.
        Afr J Lab Med. 2020 ;9(1):1193.
        BACKGROUND: In the era of evidence-based medicine, haematological reference intervals are essential for the interpretation of data for clinical decision-making, monitoring of treatment and research. It is not uncommon that reference intervals used in most African countries have been obtained from published scientific literature, textbooks, reagent/instrument manuals. OBJECTIVE: The aim of this study was to determine haematological reference intervals of healthy adults in Bamenda, Cameroon. METHODS: This was a cross-sectional study conducted between June and November 2015. Participants were voluntary blood donors at the Blood Bank Service of the Regional Hospital Bamenda aged between 18 and 65 years. The mean, median and standard deviation of the mean were calculated for each haematological parameter. The 95th percentile reference intervals were determined using the 2.5th and 97.5th percentile. The differences between gender for all the parameters were evaluated using the Kruskal-Wallis test. Significance was determined at the 95% confidence level. RESULTS: Out of a total of 340 participants, 202 (59.4%) were men and 138 (40.6%) were women. The median red blood cell, haemoglobin, haematocrit and mean cell haemoglobin concentration were significantly higher in men than women (p < 0.001). The median white blood cell, absolute lymphocytes count, absolute granulocytes and platelet counts for men were significantly lower than those for women (p < 0.011). CONCLUSION: We propose that the present established haematological reference intervals in this study should be used for clinical management of patients and interpretation of laboratory data for research in Bamenda.

      2. Low but increasing prevalence of reduced beta-lactam susceptibility among invasive group B streptococcal isolates, US population-based surveillance, 1998-2018external icon
        Kobayashi M, McGee L, Chochua S, Apostol M, Alden NB, Farley MM, Harrison LH, Lynfield R, Vagnone PS, Smelser C, Muse A, Thomas AR, Deng L, Metcalf BJ, Beall BW, Schrag SJ.
        Open Forum Infect Dis. 2021 Feb;8(2):ofaa634.
        BACKGROUND: Invasive group B Streptococcus (iGBS) isolates with mutations in the pbp2x gene that encodes penicillin binding protein 2x can have reduced beta-lactam susceptibility (RBLS) when susceptible by Clinical and Laboratory Standards Institute (CLSI) criteria. We assessed the emergence and characteristics of RBLS strains in US iGBS isolates. METHODS: We analyzed iGBS isolates from 8 multistate population-based surveillance sites from 1998 to 2018. During 1998-2014, phenotypic antimicrobial susceptibility was determined by broth microdilution; criteria for 6 antibiotics were used to identify RBLS, followed by whole-genome sequencing (WGS). WGS for all isolates was added in 2015; we used phenotypic and genotypic results of >2000 isolates to validate phenotypic RBLS criteria and genotypic predictions. Since 2016, WGS has been used to screen for RBLS with broth microdilution confirmation of predicted RBLS isolates. RESULTS: Of 28 269 iGBS isolates, 28 (0.1%) were nonsusceptible by CLSI criteria; 137 (0.5%) met RBLS criteria. RBLS isolates were detected in all Active Bacterial Core surveillance sites. The RBLS proportion increased, especially since 2013 (odds ratio, 1.17; 95% CI, 1.03-1.32); the proportion that were nonsusceptible remained stable. CONCLUSIONS: The RBSL proportion was low but increasing among US iGBS isolates. Ongoing monitoring is needed to detect emerging threats to prevention and treatment of GBS infections.

      3. Bringing the clinical laboratory into the strategy to advance diagnostic excellenceexternal icon
        Lubin IM, Astles JR, Shahangian S, Madison B, Parry R, Schmidt RL, Rubinstein ML.
        Diagnosis (Berl). 2021 Jan 5.
        OBJECTIVES: Clinical laboratory testing provides essential data for making medical diagnoses. Generating accurate and timely test results clearly communicated to the treating clinician, and ultimately the patient, is a critical component that supports diagnostic excellence. On the other hand, failure to achieve this can lead to diagnostic errors that manifest in missed, delayed and wrong diagnoses. CONTENT: Innovations that support diagnostic excellence address: 1) test utilization, 2) leveraging clinical and laboratory data, 3) promoting the use of credible information resources, 4) enhancing communication among laboratory professionals, health care providers and the patient, and 5) advancing the use of diagnostic management teams. Integrating evidence-based laboratory and patient-care quality management approaches may provide a strategy to support diagnostic excellence. Professional societies, government agencies, and healthcare systems are actively engaged in efforts to advance diagnostic excellence. Leveraging clinical laboratory capabilities within a healthcare system can measurably improve the diagnostic process and reduce diagnostic errors. SUMMARY: An expanded quality management approach that builds on existing processes and measures can promote diagnostic excellence and provide a pathway to transition innovative concepts to practice. OUTLOOK: There are increasing opportunities for clinical laboratory professionals and organizations to be part of a strategy to improve diagnoses.

      4. Differential expression of serum exosome microRNAs and cytokines in influenza A and B patients collected in the 2016 and 2017 influenza seasonsexternal icon
        Othumpangat S, Lindsley WG, Beezhold DH, Kashon ML, Burrell CN, Mubareka S, Noti JD.
        Pathogens. 2021 Feb 2;10(2).
        MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

    • Maternal and Child Health
      1. An estimated 1.4 million adults in the United States live with congenital heart defects (CHDs), yet their health outcomes are not well understood (1). Using self-reported, cross-sectional data from 1,482 respondents in the 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) (2), CDC and academic partners estimated the prevalence of comorbidities among adults with CHDs aged 20-38 years born in Arizona (AZ), Arkansas (AR), and metropolitan Atlanta, Georgia (GA) compared with the general population (aged 20-38 years) from the National Health and Nutrition Examination Survey (NHANES) during 2015-2018 (3) and the AZ, AR, and GA Behavioral Risk Factor Surveillance Systems (BRFSS) during 2016-2018 (4). Adults with CHDs were more likely than those in the general population to report cardiovascular comorbidities, such as a history of congestive heart failure (4.3% versus 0.2%) and stroke (1.4% versus 0.3%), particularly those with severe CHDs (2). Adults with CHDs were more likely to report current depressive symptoms (15.1% versus 8.5%), but less likely to report previous diagnoses of depression (14.2% versus 22.6%), asthma (12.7% versus 16.9%), or rheumatologic disease (3.2% versus 8.0%). Prevalence of noncardiovascular comorbidities was similar between adults whose CHD was considered severe and those with nonsevere CHDs. Public health practitioners and clinicians can encourage young adults with CHDs to seek appropriate medical care to help them live as healthy a life as possible.

    • Medicine
      1. Osteopathic students and graduates matching into pathology residency, 2011-2020external icon
        Jajosky RP, Coulson HC, Rosengrant AJ, Jajosky AN, Jajosky PG.
        J Am Osteopath Assoc. 2021 Feb 1;121(2):149-156.
        CONTEXT: In the past decade, two changes have affected the pathology residency match. First, the American Osteopathic Association (AOA) Match, which did not offer pathology residency, became accredited under a single graduate medical education (GME) system with the Main Residency Match (MRM), which offers pathology residency. Second, substantially fewer United States senior-year allopathic medical students (US MD seniors) matched into pathology residency. OBJECTIVE: To determine whether there were major changes in the number and percentage of osteopathic students and physicians (DOs) matching into pathology residency programs over the past decade. METHODS: Pathology match outcomes for DOs from 2011 to 2020 were obtained by reviewing AOA Match data from the National Matching Services and MRM data from the National Resident Matching Program (NRMP). The number of DOs that filled pathology positions in the MRM was divided by the total number of pathology positions filled in the MRM to calculate the percentage of pathology positions taken by DOs. RESULTS: Over the past decade, there was a 109% increase in the total number of DOs matching into pathology residency (34 in 2011 vs. 71 in 2020). During this time, there was a 23.3% increase in the total number of pathology positions filled in the MRM (476 in 2011 vs. 587 in 2020). Thus, the percentage of pathology residency positions filled by DOs increased from 7.1% in 2011 to 12.1% in 2020. The substantial increase of DOs in pathology occurred simultaneously with a 94.2% increase in the total number of DOs filling AOA/MRM "postgraduate year 1" (PGY-1) positions (3201 in 2011 vs. 6215 in 2020). Thus, the percentage of DOs choosing pathology residency has remained steady (1.06% in 2011 and 1.14% in 2020). In 2020, pathology had the third lowest percentage of filled PGY-1 residency positions taken by DOs, out of 15 major medical specialties. CONCLUSION: The proportion of DOs choosing pathology residency was stable from 2011 to 2020 despite the move to a single GME accreditation system and the stark decline in US MD seniors choosing pathology. In 2020, a slightly higher percentage of DOs (1.14%) chose pathology residency than US MD seniors (1.13%). Overall, DOs more often choose other medical specialties, including primary care. Additional studies are needed to determine why fewer US MD seniors, but not fewer DOs, are choosing pathology residency.

    • Nutritional Sciences
      1. Relation between timing of high-dose vitamin A supplementation and modified-relative-dose-response values in children 12-23 months in Ugandaexternal icon
        Pickens CM, Flores-Ayala R, Ford ND, Whitehead RD, Tanumihardjo SA, Ngalombi S, Halati S, Mapango C, Sheftel J, Jefferds ME.
        J Nutr. 2021 Feb 9.
        BACKGROUND: High-dose vitamin A (VA) supplements (VAS) can temporarily affect VA status. Hence, micronutrient surveys might need to be timed around VAS campaigns to accurately estimate VA deficiency (VAD) prevalence. Little is known about optimal timing of micronutrient surveys when the modified-relative-dose-response (MRDR) is used as a VA indicator. OBJECTIVES: We evaluated the association between days since the end of a VAS campaign and MRDR values in children aged 12-23 mo in Uganda. METHODS: We pooled data from 2 cross-sectional, population-based surveys in eastern Uganda conducted in 2015-2016 (n = 118 children). We estimated the prevalence of VAD (MRDR ≥0.060). Days since the end of a VAS campaign ("days since VAS") was calculated as the interview date minus the end date of the VAS campaign. The MRDR value was assessed using HPLC. We excluded children whose MRDR values were below the limit of detection (<0.007). We used linear regression to evaluate the association between days since VAS and log-transformed MRDR. In adjusted analyses, we controlled for potential confounders. Statistical analyses accounted for the surveys' complex design. RESULTS: The prevalence of VAD was 5.2% (95% CI: 1.1%, 9.3%). Mean days since VAS was 54.1 d (range 39-68 d). Days since VAS was not associated with log-transformed MRDR in unadjusted analyses ($\hat{\beta } = \ $0.0055; 95% CI: -0.009, 0.020; P = 0.45) or adjusted analyses ($\hat{\beta } = $ -0.0073; 95% CI: -0.024, 0.010; P = 0.39). CONCLUSIONS: MRDR measurement through a nutrition survey began as early as 1.3 mo after the end of a VAS campaign in eastern Uganda. Days since the end of a VAS campaign was not associated with MRDR in Ugandan children aged 12-23 mo. Future studies should consider longitudinal designs and evaluate time since VAS and MRDR in children of different ages and in regions with higher VAD prevalence.

    • Occupational Safety and Health
      1. OBJECTIVES: Recent technological and work organization changes have resulted in an increased prevalence of nonstandard work arrangement types. One of the consequences has been an increased prevalence of precarious work. Our objective was to generate a scale to measure work precariousness in the United States and examine the associations between this study precariousness scale with job stress, unhealthy days, and days with activity limitations among US workers from 2002 to 2014, to determine if precarious work adversely affects worker health. METHODS: Our scale was inspired by the Employment Precariousness Scale that measures work precariousness reported by salaried workers and developed for the US workforce. We used pooled cross-sectional data from 22 representative items from the General Social Survey, Quality of Work Life survey for the years 2002, 2006, 2010, and 2014. These data included 4534 observations for analysis. We used regression models to examine associations between work precariousness and job stress, unhealthy days, and days with activity limitations. RESULTS: Statistically significant positive association existed between job stress and work precariousness. Workers reporting work precariousness were more likely to experience more days in poor physical and mental health and more days with activity limitations due to health problems. CONCLUSIONS: The results of our study provide support for our precariousness scale and its suitability for assessing the health-related quality of life of workers in different work arrangements.

      2. Effects of firefighting hood design, laundering and doffing on smoke protection, heat stress and wearabilityexternal icon
        Kesler RM, Mayer A, Fent KW, Chen IC, Deaton AS, Ormond RB, Smith DL, Wilkinson A, Kerber S, Horn GP.
        Ergonomics. 2021 Feb 1:1-13.
        Firefighter hoods must provide protection from elevated temperatures and products of combustion (e.g. particulate) while simultaneously being wearable (comfortable and not interfering with firefighting activities). The purpose of this study was to quantify the impact of (1) hood design (traditional knit hood vs particulate-blocking hood), (2) repeated laundering, and (3) hood removal method (traditional vs overhead doffing) on (a) protection from soot contamination on the neck, (b) heat stress and (c) wearability measures. Using a fireground exposure simulator, 24 firefighters performed firefighting activities in realistic smoke and heat conditions using a new knit hood, new particulate-blocking hood and laundered particulate-blocking hood. Overall, soot contamination levels measured from neck skin were lower when wearing the laundered particulate-blocking hoods compared to new knit hoods, and when using the overhead hood removal process. No significant differences in skin temperature, core temperature, heart rate or wearability measures were found between the hood conditions. Practitioner Summary: The addition of a particulate-blocking layer to firefighters' traditional two-ply hood was found to reduce the PAH contamination reaching the neck but did not affect heat stress measurements or thermal perceptions. Modifying the process for hood removal resulted in a larger reduction in neck skin contamination than design modification. Abbreviations: ANOVA: analysis of variance; B: new particulate-blocking hood and PPE (PPE configuration); FES: fireground exposure simulator; GI: gastrointestinal; K: new knit hood and PPE (PPE configuration); L: laundered particulate-blocking hood and PPE (PPE configuration); LOD: limit of detection; MLE: maximum likelihood estimation; NFPA: National fire protection association; PAH: polycyclic aromatic hydrocarbon; PPE: personal protective equipment; SCBA: self-contained breathing apparatus; THL: total heat loss; TPP: thermal protective performance.

    • Parasitic Diseases
      1. Incremental impact on malaria incidence following indoor residual spraying in a highly endemic area with high standard ITN access in Mozambique: results from a cluster-randomized studyexternal icon
        Chaccour C, Zulliger R, Wagman J, Casellas A, Nacima A, Elobolobo E, Savaio B, Saifodine A, Fornadel C, Richardson J, Candrinho B, Robertson M, Saute F.
        Malar J. 2021 Feb 10;20(1):84.
        BACKGROUND: Attaining the goal of reducing the global malaria burden is threatened by recent setbacks in maintaining the effectiveness of vector control interventions partly due to the emergence of pyrethroid resistant vectors. One potential strategy to address these setbacks could be combining indoor residual spraying (IRS) with non-pyrethroids and standard insecticide-treated nets (ITNs). This study aimed to provide evidence on the incremental epidemiological benefit of using third-generation IRS product in a highly endemic area with high ITN ownership. METHODS: A cluster-randomized, open-label, parallel-arms, superiority trial was conducted in the Mopeia district in Zambezia, Mozambique from 2016 to 2018. The district had received mass distribution of alphacypermethrin ITNs two years before the trial and again mid-way. 86 clusters were defined, stratified and randomized to receive or not receive IRS with pirimiphos-methyl (Actellic®300 CS). Efficacy of adding IRS was assessed through malaria incidence in a cohort of children under five followed prospectively for two years, enhanced passive surveillance at health facilities and by community health workers, and yearly cross-sectional surveys at the peak of the transmission season. FINDINGS: A total of 1536 children were enrolled in the cohort. Children in the IRS arm experienced 4,801 cases (incidence rate of 3,532 per 10,000 children-month at risk) versus 5,758 cases in the no-IRS arm (incidence rate of 4,297 per 10,000 children-month at risk), resulting in a crude risk reduction of 18% and an incidence risk ratio of 0.82 (95% CI 0.79-0.86, p-value < 0.001). Facility and community passive surveillance showed a malaria incidence of 278 per 10,000 person-month in the IRS group (43,974 cases over 22 months) versus 358 (95% CI 355-360) per 10,000 person-month at risk in the no-IRS group (58,030 cases over 22 months), resulting in an incidence rate ratio of 0.65 (95% CI 0.60-0.71, p < 0.001). In the 2018 survey, prevalence in children under five in the IRS arm was significantly lower than in the no-IRS arm (OR 0.54, 95% CI, 0.31-0.92, p = 0.0241). CONCLUSION: In a highly endemic area with high ITN access and emerging pyrethroid resistance, adding IRS with pirimiphos-methyl resulted in significant additional protection for children under five years of age. TRIAL REGISTRATION: identifier NCT02910934, registered 22 September 2016, .

      2. Patent macracanthorhynchus ingens infection in a 17-month-old child, Ohioexternal icon
        Chancey RJ, Sapp SG, Fox M, Bishop HS, Ndubuisi M, de Almeida M, Montgomery SP, Congeni B.
        Open Forum Infect Dis. 2021 Feb;8(2):ofaa641.
        Limited data exist on human Macracanthorhynchus infections. We report an asymptomatic 17-month-old who passed eggs and an adult Macracanthorhynchus ingens worm, indicating parasite maturation and reproduction. Macracanthorhynchus ingens may have a greater capacity to mature in humans versus Macracanthorhynchus hirudinaceus.

      3. The recent increase of reported cyclosporiasis outbreaks associated with fresh produce has highlighted the need for understanding environmental transmission of Cyclospora cayetanensis in agricultural settings and facilities. Conducting such environmental investigations necessitates robust sample collection and analytical methods to detect C. cayetanensis in water samples. This study evaluated three sample collection methods for recovery of C. cayetanensis oocysts from water samples during seeded recovery experiments. Two filtration-based methods, dead-end ultrafiltration (DEUF) and USEPA Method 1623.1, were evaluated for oocyst recovery from irrigation water. A non-filter-based method, continuous flow centrifugation (CFC), was evaluated separately for recovery from creek water and spent produce wash water. Median C. cayetanensis recovery efficiencies were 17% for DEUF and 16–22% for Method 1623.1. The DEUF method proved to be more robust than Method 1623.1, as the recovery efficiencies were less variable and the DEUF ultrafilters were capable of filtering larger volumes of high-turbidity water without clogging. Median C. cayetanensis recovery efficiencies for CFC were 28% for wash water and 63% for creek water, making it a viable option for processing water with high turbidity or organic matter. The data from this study demonstrate the capability of DEUF and CFC as filter-based and non-filter-based options, respectively, for the recovery of C. cayetanensis oocysts from environmental and agricultural waters.

      4. Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leoneexternal icon
        Lahuerta M, Sutton R, Mansaray A, Eleeza O, Gleason B, Akinjeji A, Jalloh MF, Toure M, Kassa G, Meshnick SR, Deutsch-Feldman M, Parmley L, Friedman M, Smith SJ, Rabkin M, Steinhardt L.
        Malar J. 2021 Feb 6;20(1):74.
        BACKGROUND: Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. METHODS: This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15-17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3-15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. RESULTS: Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2-7%]; 11% post-IPTi [95%CI 8-15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. CONCLUSIONS: Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme.

      5. Low prevalence of highly sulfadoxine-resistant dihydropteroate synthase alleles in Plasmodium falciparum isolates in Beninexternal icon
        Svigel SS, Adeothy A, Kpemasse A, Houngbo E, Sianou A, Saliou R, Patton ME, Dagnon F, Halsey ES, Tchevoede A, Udhayakumar V, Lucchi NW.
        Malar J. 2021 Feb 5;20(1):72.
        BACKGROUND: In 2004, in response to high levels of treatment failure associated with sulfadoxine-pyrimethamine (SP) resistance, Benin changed its first-line malaria treatment from SP to artemisinin-based combination therapy for treatment of uncomplicated Plasmodium falciparum malaria. Resistance to SP is conferred by accumulation of single nucleotide polymorphisms (SNPs) in P. falciparum genes involved in folate metabolism, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. Because SP is still used for intermittent preventive treatment in pregnant women (IPTp) and seasonal malaria chemoprevention (SMCP) in Benin, the prevalence of Pfdhfr and Pfdhps SNPs in P. falciparum isolates collected in 2017 were investigated. METHODS: This study was carried out in two sites where the transmission of P. falciparum malaria is hyper-endemic: Klouékanmey and Djougou. Blood samples were collected from 178 febrile children 6-59 months old with confirmed uncomplicated P. falciparum malaria and were genotyped for SNPs associated with SP resistance. RESULTS: The Pfdhfr triple mutant IRN (N51I, C59R, and S108N) was the most prevalent (84.6%) haplotype and was commonly found with the Pfdhps single mutant A437G (50.5%) or with the Pfdhps double mutant S436A and A437G (33.7%). The quintuple mutant, Pfdhfr IRN/Pfdhps GE (A437G and K540E), was rarely observed (0.8%). The A581G and A613S mutant alleles were found in 2.6 and 3.9% of isolates, respectively. Six isolates (3.9%) were shown to harbour a mutation at codon I431V, recently identified in West African parasites. CONCLUSIONS: This study showed that Pfdhfr triple IRN mutants are near fixation in this population and that the highly sulfadoxine-resistant Pfdhps alleles are not widespread in Benin. These data support the continued use of SP for chemoprevention in these study sites, which should be complemented by periodic nationwide molecular surveillance to detect emergence of resistant genotypes.

    • Program Evaluation
      1. Validation of the prevention impacts simulation model (PRISM)external icon
        Yarnoff B, Honeycutt A, Bradley C, Khavjou O, Bates L, Bass S, Kaufmann R, Barker L, Briss P.
        Prev Chronic Dis. 2021 Feb 4;18:E09.
        INTRODUCTION: Demonstrating the validity of a public health simulation model helps to establish confidence in the accuracy and usefulness of a model's results. In this study we evaluated the validity of the Prevention Impacts Simulation Model (PRISM), a system dynamics model that simulates health, mortality, and economic outcomes for the US population. PRISM primarily simulates outcomes related to cardiovascular disease but also includes outcomes related to other chronic diseases that share risk factors. PRISM is openly available through a web application. METHODS: We applied the model validation framework developed independently by the International Society of Pharmacoeconomics and Outcomes Research and the Society for Medical Decision Making modeling task force to validate PRISM. This framework included model review by external experts and quantitative data comparison by the study team. RESULTS: External expert review determined that PRISM is based on up-to-date science. One-way sensitivity analysis showed that no parameter affected results by more than 5%. Comparison with other published models, such as ModelHealth, showed that PRISM produces lower estimates of effects and cost savings. Comparison with surveillance data showed that projected model trends in risk factors and outcomes align closely with secular trends. Four measures did not align with surveillance data, and those were recalibrated. CONCLUSION: PRISM is a useful tool to simulate the potential effects and costs of public health interventions. Results of this validation should help assure health policy leaders that PRISM can help support community health program planning and evaluation efforts.

    • Public Health Leadership and Management
      1. Evaluation of a new field epidemiology training program intermediate course to strengthen public health workforce capacity in Tanzaniaexternal icon
        Wilson K, Juya A, Abade A, Sembuche S, Leonard D, Harris J, Perkins S, Chale S, Bakari M, Mghamba J, Kohler P.
        Public Health Rep. 2021 Feb 4.
        OBJECTIVES: Sub-Saharan Africa faces a shortage of skilled epidemiologists to prevent, detect, and respond to health threats. Tanzania has implemented one of the first Centers for Disease Control and Prevention Field Epidemiology Training Program (FETP) Intermediate courses in Africa. This course aims to strengthen health workforce capacity in surveillance system assessment, outbreak investigation, and evaluation, prioritizing HIV control. We conducted an outcome evaluation of this new course. METHODS: We used a pre/post evaluation design using data from 4 cohorts of trainees who took the FETP Intermediate course from 2017 to 2020. We conducted knowledge assessments before and after each cohort and combined those results. Outcomes included knowledge and self-rated competency and trends in integrated disease surveillance and response (IDSR) data. We collected data through tests, field assignments, exit interviews, and data audits. We compared the mean change in pre-/posttest scores using linear regression and 95% CIs. We used content analysis to summarize exit interviews. RESULTS: Fifty-three FETP trainees from 10 regions enrolled in the FETP Intermediate course, and 52 (99.0%) completed the course. We found substantial increases in mean knowledge (44.0 to 68.0 points) and self-rated competency (4.14 to 4.43) scores before and after the course. Trainees evaluated 52 surveillance systems and 52 district HIV care programs, and 39 (75.0%) trainees participated in outbreak investigations. From before to after cohort 1, timeliness and completeness of IDSR reports increased from 4.2% to 52.1% and from 27.4% to 76.5%, respectively. Course strengths were quality of instruction, individualized mentoring, and practical skills gained. Challenges were mentor availability, limited time for data analysis practice, and balancing work and field assignments. CONCLUSIONS: The Tanzania FETP Intermediate course substantially improved trainee knowledge and helped to improve local data quality and reporting. This course is a promising model to strengthen subnational capacity to prevent, detect, and respond to public health threats in Africa.

    • Reproductive Health
      1. Maternal transport: an opportunity to improve the system of risk-appropriate careexternal icon
        DeSisto CL, Oza-Frank R, Goodman D, Conrey E, Shellhaas C.
        J Perinatol. 2021 Feb 5.
        OBJECTIVE: To assess how often maternal transport preceded pregnancy-related deaths and describe contributing factors and recommendations related to maternal transport. STUDY DESIGN: We used Ohio maternal mortality review committee (MMRC) data from 2010 to 2016. We defined two transport types among pregnancy-related deaths: field to hospital and hospital to hospital. We examined deaths determined by the MMRC to be potentially preventable by transfer to a higher level of care and described contributing factors and recommendations. RESULT: Among 136 pregnancy-related deaths, 56 (41.2%) were transported. Among 15 deaths identified as potentially preventable by transfer to a higher level of care, 5 were transported between hospitals. Contributing factors for 14 deaths included inadequate response by Emergency Medical Services and lack of transport to a higher level of care. CONCLUSION: Our results suggest opportunities for examining modification and adherence to existing protocols. Improving risk-appropriate maternal care systems is important for preventing pregnancy-related deaths.

    • Substance Use and Abuse

      1. A brief overview of the national outbreak of e-cigarette, or vaping, product use-associated lung injury and the primary causesexternal icon
        Kiernan E, Click ES, Melstrom P, Evans ME, Layer MR, Weissman DN, Reagan-Steiner S, Wiltz JL, Hocevar S, Goodman AB, Twentyman E.
        Chest. 2021 Jan;159(1):426-431.

      2. Trends and geographic patterns in drug and synthetic opioid overdose deaths - United States, 2013-2019external icon
        Mattson CL, Tanz LJ, Quinn K, Kariisa M, Patel P, Davis NL.
        MMWR Morb Mortal Wkly Rep. 2021 Feb 12;70(6):202-207.
        Deaths involving synthetic opioids other than methadone (synthetic opioids), which largely consist of illicitly manufactured fentanyl; psychostimulants with abuse potential (e.g., methamphetamine); and cocaine have increased in recent years, particularly since 2013 (1,2). In 2019, a total of 70,630 drug overdose deaths occurred, corresponding to an age-adjusted rate of 21.6 per 100,000 population and a 4.3% increase from the 2018 rate (20.7) (3). CDC analyzed trends in age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, heroin, and prescription opioids during 2013-2019, as well as geographic patterns in synthetic opioid- and psychostimulant-involved deaths during 2018-2019. From 2013 to 2019, the synthetic opioid-involved death rate increased 1,040%, from 1.0 to 11.4 per 100,000 age-adjusted (3,105 to 36,359). The psychostimulant-involved death rate increased 317%, from 1.2 (3,627) in 2013 to 5.0 (16,167) in 2019. In the presence of synthetic opioid coinvolvement, death rates for prescription opioids, heroin, psychostimulants, and cocaine increased. In the absence of synthetic opioid coinvolvement, death rates increased only for psychostimulants and cocaine. From 2018 to 2019, the largest relative increase in the synthetic opioid-involved death rate occurred in the West (67.9%), and the largest relative increase in the psychostimulant-involved death rate occurred in the Northeast (43.8%); these increases represent important changes in the geographic distribution of drug overdose deaths. Evidence-based prevention and response strategies including substance use disorder treatment and overdose prevention and response efforts focused on polysubstance use must be adapted to address the evolving drug overdose epidemic.

    • Zoonotic and Vectorborne Diseases
      1. OBJECTIVES: Although tick-borne diseases account for a large number of health care visits in the United States, clinical practices for tick bite and Lyme disease treatment and prevention are not well understood. The objective of this study was to better understand factors associated with clinical practices related to tick bites and Lyme disease. METHODS: In 2013-2015, questions about tick-bite evaluation, Lyme disease diagnosis and treatment, appropriate use of Lyme disease testing, and tick-bite prevention were included in Porter Novelli's DocStyles survey, a nationally representative annual web-based survey of health care providers. We performed analyses of responses by provider license type and state-level incidence (high or low) of Lyme disease in 2019. RESULTS: A total of 4517 providers were surveyed across the 3 study years. Overall, 80.9% of providers reported that they had evaluated at least 1 patient for a tick bite, 47.6% had diagnosed at least 1 patient with Lyme disease, and 61.9% had treated at least 1 patient for Lyme disease in the previous year. Providers from states with a high incidence of Lyme disease saw more patients for tick bites and Lyme disease than providers from states with a low incidence of Lyme disease. Few providers correctly chose Lyme disease testing as clinically useful in the hypothetical case of a patient from a state with a high incidence of Lyme disease with an arthritic knee (36.0%) or with new-onset atrioventricular block (39.5%), and respondents across all provider types incorrectly chose testing when not clinically indicated. Most providers (69.7%) reported routinely recommending tick-bite prevention methods to patients. CONCLUSIONS: Many providers evaluate patients for tick bites and treat patients for Lyme disease, but knowledge about appropriate testing is low. Providers may benefit from tailored education about appropriate Lyme disease diagnosis, testing, and effective tick-bite prevention.

      2. In the United States, exposure to human-biting ixodid ticks can occur while spending time on residential properties or in neighborhood green spaces as well as during recreational or occupational activities on public lands. Human-biting tick species collectively transmit >15 species of pathogenic microorganisms and the national burden of tick-borne diseases is increasing. The prospect of a new Lyme disease vaccine for use in humans provides hope for substantial reduction in the >450,000 estimated annual cases of Lyme disease but this breakthrough would not reduce cases of other tick-borne diseases, such as anaplasmosis, babesiosis, ehrlichiosis, spotted fever group rickettsiosis, and Powassan encephalitis. One intriguing question is to what extent a new Lyme disease vaccine would impact the use of personal protection measures acting broadly against tick-bites. The main tick vector for Lyme disease spirochetes in the eastern United States, Ixodes scapularis, also transmits causative agents of anaplasmosis, babesiosis, and Powassan encephalitis; and this tick species co-occurs with other human-biting vectors such as Amblyomma americanum and Dermacentor variabilis. It therefore is important that a new Lyme disease vaccine does not result in reduced use of tick-bite prevention measures, such as tick repellents, permethrin-treated clothing, and frequent tick checks. Another key issue is the continuing problem with tick exposure on residential properties, which represents a heavily used outdoor environment the residents cannot reasonably avoid and where they tend to spend large amounts of time outside. As it may not be realistic to keep up daily vigilance with personal protective measures against tick-bites on residential properties during many months of every year, homeowners may also consider the option to suppress host-seeking ticks by means of deer fencing, landscaping, vegetation management, and use of products to kill host-seeking ticks or ticks infesting rodents. When considering the full range of options for actions that can be taken to suppress host-seeking ticks on residential properties, it is clear that individual homeowners face a difficult and bewildering task in deciding what to do based on very general guidance from public health agencies (developed without the benefit of a strong evidence base) and often without ready access to local public health professionals experienced in tick control. This situation is not satisfactory but cannot be corrected without first addressing knowledge gaps regarding the impact of peridomestic tick control measures on host-seeking ticks, human tick-bites, and tick-borne diseases. In parallel with this effort, there also is a need to increase the local public health workforce with knowledge of and experience with tick control to provide better access for homeowners to sound and objective advice regarding tick control on their properties based on key characteristics of the landscaping, habitat composition, and use patterns by wild animal tick hosts as well as the residents.

      3. Human-tick encounters as a measure of tickborne disease risk in lyme disease endemic areasexternal icon
        Hook SA, Nawrocki CC, Meek JI, Feldman KA, White JL, Connally NP, Hinckley AF.
        Zoonoses Public Health. 2021 Feb 7.
        Entomological measures have long served as proxies for human risk of Lyme disease (LD) and other tickborne diseases (TBDs) in endemic areas of the United States, despite conflicting results regarding the correlation between these measures and human disease outcomes. Using data from a previous TBD intervention study in Connecticut, Maryland and New York, we evaluated whether human-tick encounters can serve as an accurate proxy for risk of TBDs in areas where LD and other Ixodes scapularis-transmitted infections are common. Among 2,590 households consisting of 4,210 individuals, experiencing a tick encounter was associated with an increased risk of both self-reported (RR = 3.17, 95% CI: 2.05, 4.91) and verified TBD (RR = 2.60, 95% CI: 1.39, 4.84) at the household level. Household characteristics associated with experiencing any tick encounter were residence in Connecticut (aOR = 1.86, 95% CI: 1.38, 2.51) or New York (aOR = 1.66, 95% CI: 1.25, 2.22), head of household having a graduate level education (aOR = 1.46, 95% CI: 1.04, 2.08), owning a pet (aOR = 1.80, 95% CI: 1.46, 2.23) and a property size of 2 acres or larger (aOR = 2.30, 95% CI: 1.42, 3.70). Results for individual characteristics were similar to those for households. Future prevention studies in LD endemic areas should consider using human-tick encounters as a robust proxy for TBD risk.

      4. Persistence of Ebola virus in semen among Ebola virus disease survivors in Sierra Leone: A cohort study of frequency, duration, and risk factorsexternal icon
        Thorson AE, Deen GF, Bernstein KT, Liu WJ, Yamba F, Habib N, Sesay FR, Gaillard P, Massaquoi TA, McDonald SL, Zhang Y, Durski KN, Singaravelu S, Ervin E, Liu H, Coursier A, Marrinan JE, Ariyarajah A, Carino M, Formenty P, Ströher U, Lamunu M, Wu G, Sahr F, Xu W, Knust B, Broutet N.
        PLoS Med. 2021 Feb;18(2):e1003273.
        BACKGROUND: Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. METHODS AND FINDINGS: In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. CONCLUSIONS: In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.

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