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Volume 12, Issue 9, March 17, 2020

CDC Science Clips: Volume 12, Issue 9, March 17, 2020

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

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Projected estimates of cancer in Canada in 2020external icon
        Brenner DR, Weir HK, Demers AA, Ellison LF, Louzado C, Shaw A, Turner D, Woods RR, Smith LM.
        Cmaj. 2020 Mar 2;192(9):E199-e205.
        BACKGROUND: Cancer projections to the current year help in policy development, planning of programs and allocation of resources. We sought to provide an overview of the expected incidence and mortality of cancer in Canada in 2020 in follow-up to the Canadian Cancer Statistics 2019 report. METHODS: We obtained incidence data from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2015). Mortality data (1984-2015) were obtained from the Canadian Vital Statistics - Death Database. All databases are maintained by Statistics Canada. Cancer incidence and mortality counts and age-standardized rates were projected to 2020 for 23 cancer types by sex and geographic region (provinces and territories) for all ages combined. RESULTS: An estimated 225 800 new cancer cases and 83 300 cancer deaths are expected in Canada in 2020. The most commonly diagnosed cancers are expected to be lung overall (29 800), breast in females (27 400) and prostate in males (23 300). Lung cancer is also expected to be the leading cause of cancer death, accounting for 25.5% of all cancer deaths, followed by colorectal (11.6%), pancreatic (6.4%) and breast (6.1%) cancers. Incidence and mortality rates will be generally higher in the eastern provinces than in the western provinces. INTERPRETATION: The number of cancer cases and deaths remains high in Canada and, owing to the growing and aging population, is expected to continue to increase. Although progress has been made in reducing deaths for most major cancers (breast, prostate and lung), there has been limited progress for pancreatic cancer, which is expected to be the third leading cause of cancer death in Canada in 2020. Additional efforts to improve uptake of existing programs, as well as to advance research, prevention, screening and treatment, are needed to address the cancer burden in Canada.

    • Communicable Diseases
      • Expansion of HIV preexposure prophylaxis to 35 PEPFAR-supported early program adopters, October 2016-September 2018external icon
        Djomand G, Bingham T, Benech I, Muthui M, Savva H, Alamo S, Manopaiboon C, Wheeler T, Mital S.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 28;69(8):212-215.
        The U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the largest bilateral funder of human immunodeficiency virus (HIV) prevention and control programs worldwide, currently supports implementation of preexposure prophylaxis (PrEP) to reduce HIV incidence among persons at substantial risk for infection, including female sex workers, men who have sex with men (MSM), and transgender women (hereafter referred to as key populations). Recent estimates suggest that 54% of all global new HIV infections in 2018 occurred among key populations and their sexual partners (1). In 2016, PEPFAR began tracking initiation of PrEP by key populations and other groups at high risk (2). The implementation and scale-up of PrEP programs across 35 PEPFAR-supported country or regional programs* was assessed by determining the number of programs reporting any new PrEP clients during each quarter from October 2016 to September 2018. As of September 2018, only 15 (43%) PEPFAR-supported country or regional programs had implemented PrEP programs; however, client volume increased by 3,351% over the assessment period in 15 country or regional programs. Scale-up of PrEP among general population clients (5,255%) was nearly three times that of key population clients (1,880%). Among key populations, the largest increase (3,518%) occurred among MSM. Factors that helped drive the success of these PrEP early adopter programs included initiation of national, regional, and multilateral stakeholder meetings; engagement of ministries of health and community advocates; revision of HIV treatment guidelines to include PrEP; training for HIV service providers; and establishment of drug procurement policies. These best practices can help facilitate PrEP implementation, particularly among key populations, in other country or regional programs to reduce global incidence of HIV infection.

    • Community Health Services
      • Sexual behaviors, referral to sexual health services, and use of sexual health services among transgender high school studentsexternal icon
        Andrzejewski J, Pampati S, Johns MM, Sheremenko G, Lesesne C, Rasberry CN.
        J Sch Health. 2020 Mar 3.
        BACKGROUND: Transgender adolescents are at increased risk for negative sexual health outcomes compared to their cisgender peers. METHODS: Using data from 10,231 students from 7 high schools in a large, urban school district, our analysis compared sexual behaviors, referral to sexual health services by school staff, and use of sexual health services between transgender and cisgender students. We used propensity score matching to create a comparable sample of transgender and cisgender students and logistic regression models to examine how gender identity was associated with aforementioned outcomes. RESULTS: Transgender students were more likely to have ever had sex, less likely to have used a condom at last sex, and more likely to have been referred for human immunodeficiency virus (HIV) testing, sexually transmitted disease (STD) testing, and other sexual health services than cisgender students. Transgender students were no more likely than cisgender students to have tested for HIV or STDs. CONCLUSIONS: These findings underscore the need for understanding the risk perceptions held by transgender students and for prevention efforts that are inclusive for all gender identities. Research is needed to understand if school-based sexual health interventions such as staff referrals for sexual health services are effective for transgender students.

    • Health Disparities
      • Changes in disparities in estimated HIV incidence rates among black, Hispanic/Latino, and white men who have sex with men (MSM) in the United States, 2010-2015external icon
        McCree DH, Williams AM, Chesson HW, Beer L, Jeffries WL, Lemons A, Prather C, Sutton MY, McCray E.
        J Acquir Immune Defic Syndr. 2019 May 1;81(1):57-62.
        BACKGROUND: During 2008-2015, the estimated annual HIV incidence rate in the United States decreased for each transmission risk category, except for men who have sex with men (MSM). Racial/ethnic disparities exist, with higher incidence rates for Black and Hispanic/Latino MSM. SETTING: This analysis examines changes, 2010-2015, in disparities of HIV incidence among Black, Hispanic/Latino and White MSM. METHODS: We compared results from the rate ratio, rate difference, weighted and unweighted index of disparity, and population attributable proportion. We calculated incidence rates for MSM using HIV surveillance data and published estimates of the MSM population in the United States. We generated 95% confidence intervals for each measure and used the Z statistic and associated P values to assess statistical significance. FINDINGS: Results from all but one measure, Black-to-White rate difference, indicate that racial/ethnic disparities increased during 2010-2015; not all results were statistically significant. There were statistically significant increases in the Hispanic/Latino-to-White MSM incidence rate ratio (29%, P < 0.05), weighted index of disparity with the rate for White MSM as the referent group (9%, P < 0.05), and the population attributable proportion index (10%, P < 0.05). If racial/ethnic disparities among MSM had been eliminated, a range of 55%-61% decrease in overall MSM HIV incidence would have been achieved during 2010-2015. CONCLUSIONS: A large reduction in overall annual HIV incidence among MSM can be achieved by eliminating racial/ethnic disparities among MSM. Removing social and structural causes of racial/ethnic disparities among MSM can be effective in reducing overall annual HIV incidence among MSM.

    • Health Economics
      • Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysisexternal icon
        Lim AG, Walker JG, Mafirakureva N, Khalid GG, Qureshi H, Mahmood H, Trickey A, Fraser H, Aslam K, Falq G, Fortas C, Zahid H, Naveed A, Auat R, Saeed Q, Davies CF, Mukandavire C, Glass N, Maman D, Martin NK, Hickman M, May MT, Hamid S, Loarec A, Averhoff F, Vickerman P.
        Lancet Glob Health. 2020 Mar;8(3):e440-e450.
        BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13.8 million (95% UI 13.4-14.1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26.5% (22.5-30.7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged >/=30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46.8% and decrease incidence by 50.8% (95% UI 46.1-55.0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8.1 billion, reducing to $3.9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9.0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID.

    • Healthcare Associated Infections
      • Burden of candidemia in the United States, 2017external icon
        Tsay SV, Mu Y, Williams S, Epson E, Nadle J, Bamberg WM, Barter DM, Johnston HL, Farley MM, Harb S, Thomas S, Bonner LA, Harrison LH, Hollick R, Marceaux K, Mody RK, Pattee B, Shrum Davis S, Phipps EC, Tesini BL, Gellert AB, Zhang AY, Schaffner W, Hillis S, Ndi D, Graber CR, Jackson BR, Chiller T, Magill S, Vallabhaneni S.
        Clin Infect Dis. 2020 Feb 28.
        BACKGROUND: Candidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States. METHODS: In 2017, the Centers for Disease Control and Prevention (CDC) conducted active population-based surveillance for candidemia through the Emerging Infections Program (EIP) in 45 counties in nine states encompassing ~17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality was estimated by extrapolating surveillance area cases to national numbers using 2017 national census data. RESULTS: We identified 1,226 candidemia cases across nine surveillance sites in 2017. Based on this, we estimated 22,660 (95% confidence interval [CI]: 20,210-25,110) cases of candidemia occurred in the United States in 2017. Overall estimated incidence was 7.0 cases per 100,000 persons, with highest rates in adults >/=65 years (20.1/100,000), males (7.9/100,000), and those of black race (12.3/100,000). An estimated 3,380 (95% CI: 1,318-5,442) deaths occurred within seven days of a positive Candida blood culture and 5,628 (95% CI: 2,465-8,791) deaths occurred during the hospitalization with candidemia. CONCLUSIONS: Our analysis highlights the substantial burden of candidemia in the U.S. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions.

    • Immunity and Immunization
      • Vaccine effectiveness against influenza hospitalization among children in the United States, 2015-2016external icon
        Feldstein LR, Ogokeh C, Rha B, Weinberg GA, Staat MA, Selvarangan R, Halasa NB, Englund JA, Boom JA, Azimi PH, Szilagyi PG, McNeal M, Harrison CJ, Williams JV, Klein EJ, Sahni LC, Singer MN, Lively JY, Payne DC, Fry AM, Patel M, Campbell AP.
        J Pediatric Infect Dis Soc. 2020 Feb 28.
        BACKGROUND: Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children. METHODS: We included children aged 6 months-17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015-2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% x (1 - odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression. RESULTS: Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children </= 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%-71%) against any influenza-associated hospitalization, 68% (95% CI, 36%-84%) for A(H1N1)pdm09, and 44% (95% CI, -1% to 69%) for B viruses. CONCLUSIONS: These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.

    • Substance Use and Abuse
      • E-cigarette advertising expenditures in the United States, 2014-2018external icon
        Ali FR, Marynak KL, Kim Y, Binns S, Emery SL, Gomez Y, King BA.
        Tob Control. 2020 Feb 27.
        BACKGROUND: Tobacco product advertising has been shown to reach youth and promote initiation. This study assessed trends in e-cigarette advertising expenditures in the USA during 2014-2018, overall and by manufacturer and media type. METHODS: Data came from Kantar Media, which provides information on US advertising expenditures, including for e-cigarettes. Advertising expenditures were estimated as the dollar amount spent by e-cigarette companies to purchase advertising space in print, television, Internet, radio and outdoors. Dollar amounts were adjusted to 2017 dollars. Trends in e-cigarette advertising expenditures during 2014-2018 were analysed using Joinpoint regression overall, by media type, and by manufacturers based on 2017-2018 national sales. RESULTS: Total e-cigarette advertising expenditures in print, radio, television, Internet and outdoors decreased substantially from US$133 million in 2014 to US$48 million in 2017, followed by an increase to US$110 million in 2018. By media type, expenditures were highest for print advertising, irrespective of year. By manufacturer, Altria had the highest e-cigarette advertising expenditures, totalling over US$134 million during 2014-2018. Imperial Tobacco had the second highest, totalling over US$85 million during 2014-2018, while JUUL Labs had the highest single-year expenditures, spending over US$73 million in 2018 alone. CONCLUSIONS: E-cigarette advertising expenditures have been volatile in the USA, with declines in traditional advertising venues during 2014-2017 that may reflect a shift towards social media. However, an increase occurred in 2018 that is likely reflective of advertising by newer manufacturers. Continued monitoring of e-cigarette advertising is important to inform tobacco control strategies.

    • Zoonotic and Vectorborne Diseases
      • Covid-19 - navigating the unchartedexternal icon
        Fauci AS, Lane HC, Redfield RR.
        N Engl J Med. 2020 Feb 28.

      • Changing contact patterns over disease progression: Nipah virus as a case studyexternal icon
        Lee KH, Nikolay B, Sazzad HM, Hossain MJ, Khan A, Rahman M, Satter SM, Nichol ST, Klena JD, Pulliam JR, Kilpatrick AM, Sultana S, Afroj S, Daszak P, Luby S, Cauchemez S, Salje H, Gurley E.
        J Infect Dis. 2020 Mar 2.
        Contact patterns play a key role in disease transmission, and variation in contacts during the course of illness can influence transmission, particularly when accompanied by changes in host infectiousness. We used surveys among 1,642 contacts of 94 Nipah case-patients in Bangladesh to determine how contact patterns (physical and with bodily fluids) changed as disease progressed in severity. The number of contacts increased with severity and, for case-patients who died, peaked on the day of death. Given transmission has only been observed among fatal Nipah cases, our findings suggest changes in contact patterns during illness contribute to risk of infection.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Trends in acute myocardial infarction by race and ethnicityexternal icon
        Chi GC, Kanter MH, Li BH, Qian L, Reading SR, Harrison TN, Jacobsen SJ, Scott RD, Cavendish JJ, Lawrence JM, Tartof SY, Reynolds K.
        J Am Heart Assoc. 2020 Mar 3;9(5):e013542.
        Background Trends in acute myocardial infarction (AMI) incidence rates for diverse races/ethnicities are largely unknown, presenting barriers to understanding the role of race/ethnicity in AMI occurrence. Methods and Results We identified AMI hospitalizations for Kaiser Permanente Southern California members, aged >/=35 years, during 2000 to 2014 using discharge diagnostic codes. We excluded hospitalizations with missing race/ethnicity information. We calculated annual incidence rates (age and sex standardized to the 2010 US census population) for AMI, ST-segment-elevation myocardial infarction, and non-ST-segment-elevation myocardial infarction by race/ethnicity (Hispanic and non-Hispanic racial groups: Asian or Pacific Islander, black, and white). Using Poisson regression, we estimated annual percentage change in AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction incidence by race/ethnicity and AMI incidence rate ratios between race/ethnicity pairs, adjusting for age and sex. We included 18 630 776 person-years of observation and identified 44 142 AMI hospitalizations. During 2000 to 2014, declines in AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction were 48.7%, 34.2%, and 69.8%, respectively. Age- and sex-standardized AMI hospitalization rates/100 000 person-years declined for Hispanics (from 307 to 162), Asians or Pacific Islanders (from 271 to 158), blacks (from 347 to 199), and whites (from 376 to 189). Annual percentage changes ranged from -2.99% to -4.75%, except for blacks, whose annual percentage change was -5.32% during 2000 to 2009 and -1.03% during 2010 to 2014. Conclusions During 2000 to 2014, AMI, non-ST-segment-elevation myocardial infarction, and ST-segment-elevation myocardial infarction hospitalization incidence rates declined substantially for each race/ethnic group. Despite narrowing rates among races/ethnicities, differences persist. Understanding these differences can help identify unmet needs in AMI prevention and management to guide targeted interventions.

      2. Objective: To conduct educational and promotional outreach activities to general neurologists and to increase self-enrollment of persons with amyotrophic lateral sclerosis (ALS) in the National ALS Registry (Registry). Methods: A multicomponent project to educate neurologists and increase Registry self-enrollment was delivered. Project components consisted of phone calls, mailings, train-the-trainer presentations, and key informant interviews. Project-specific metrics, continuing education enrollment, and Registry self-enrollment data were analyzed to measure project efficacy. Results: Mailings were sent to 1561 neurologists in 6 states during 2015 to 2016. Sixty-five percent of responding neurologists remembered the mailing 3 months after receipt. Of providers who saw patients with ALS in the 3-month period, 60% read the provider guide, 22% distributed a patient guide, and 15% advised a patient to self-enroll. No changes in self-enrollment rates were observed. Conclusion: Targeted mailings to providers can be used to educate them about the Registry; however, most providers did not distribute materials to patients with ALS. Increases in providers receiving Registry material did not lead to increases in patient self-enrollment. Practice Implications: General neurologists have competing priorities, and they see patients with ALS infrequently. Neurologists could be the appropriate channel to distribute Registry information to patients, but they are not the appropriate resource to assist patients with self-enrollment. Engaging the support staff of busy specialists can help increase research response rates and information distribution. The lessons learned from this project can be applied to other rare conditions and disease specialists.

    • Communicable Diseases
      1. High hepatitis C virus infection among female sex workers in Viet Nam: strong correlation with HIV and injection drug useexternal icon
        Le LN, O'Connor S, Tran TH, Maher L, Kaldor J, Sabin K, Tran HV, Tran QD, Ho VA, Nguyen TA.
        Western Pac Surveill Response J. 2019 Jul-Sep;10(3):9-18.
        Objective: The World Health Organization's guidelines on viral hepatitis testing and treatment recommend prioritizing high prevalence groups. Hepatitis C virus (HCV) infection disproportionately affects people who inject drugs and men who have sex with men, but data on female sex workers (FSW) are limited. The study aimed to determine active HCV infection and risk factors associated with HCV exposure among Vietnamese FSW. Methods: We surveyed 1886 women aged >/= 18 years from Haiphong, Hanoi and Ho Chi Minh City who had sold sex in the last month. We tested for HCV antibody and HCV core antigen as markers for exposure to HCV and active infection, respectively. Results: Across these provinces, high prevalence of HCV exposure (8.8-30.4%) and active infection (3.6-22.1%) were observed. Significant associations with HCV exposure were HIV infection (aOR = 23.7; 95% CI: 14.8-37.9), injection drug use (aOR = 23.3; 95% CI: 13.1-41.4), history of compulsory detention (aOR = 2.5; 95% CI: 1.4-4.2) and having more than 10 sex clients in the last month (aOR = 1.9; 95% CI: 1.2-3.2). Among FSW who reported never injecting drugs, HIV infection (aOR = 24.2; 95% CI: 14.8-39.4), a history of non-injection drug use (aOR = 3.3, CI: 1.8-5.7), compulsory detention (aOR = 2.2; 95% CI: 1.2-4.0) and having over 10 sex clients in the last month (aOR = 2.2, 95% CI: 1.3-3.7) were independently associated with HCV exposure. Discussion: FSW have elevated HCV risks through sex- and drug-related pathways. These findings highlight the need to offer FSW-targeted HCV interventions and ensure their access to HIV prevention and treatment.

      2. Implementation of an active case management network to identify HIV-positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018external icon
        Lolekha R, Pavaputanon P, Puthanakit T, Martin M, Kosalaraksa P, Petdachai W, Borkird T, Hansudewechakul R, Rojanawiwat A, Boonsuk S, Samleerat T, Ongwandee S.
        J Int AIDS Soc. 2020 Feb;23(2):e25450.
        INTRODUCTION: Early initiation of antiretroviral therapy (ART) can reduce HIV-related morbidity and mortality in HIV-positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre-ACC). METHODS: Thailand's 2014 HIV Treatment Guidelines recommend that HIV-exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV-positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time-to-ART initiation. RESULTS: The uptake of EID increased from 64% (pre-ACC) to >95% in 2018 (ACC). The number of HIV-positive infants born declined from 429 cases (pre-ACC) to 267 cases (ACC). Median age at the first-positive PCR declined from 75 days (pre-ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV-positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001). CONCLUSIONS: An innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case-managed PCR notification and follow-up, may speed ART initiation in other settings.

      3. Black and Latino men who have sex with men (BLMSM) accounted for 53% of males newly diagnosed with HIV in New York City (NYC) in 2015. Despite increased HIV testing efforts with BLMSM in the U.S. and specifically in areas like NYC with high rates of HIV, data show suboptimal testing among BLMSM in some high-prevalence areas of the country. Few reports describe the HIV testing perspectives of BLMSM at risk of HIV acquisition. We sought to obtain information from BLMSM at possible risk of HIV infection to learn about their HIV testing perspectives. During 2011-2012, we obtained baseline and 3-month follow-up computer questionnaire data and in-depth interview data from self-identified BLMSM in the NYC area who had not been recently tested for HIV. Quantitative demographic data were analyzed using SAS. Qualitative interview responses regarding personal experiences and thoughts about HIV testing were analyzed using applied thematic analysis. Overall, 109 BLMSM participated; 51 (46.85%) had never been tested for HIV; 43 (39.4%) were aged 18-29 years; 51 (46.8%) reported condomless sex at last sex. Qualitative analyses revealed three major themes: (1) perceptions on the NY State HIV opt-out HIV testing law; (2) HIV testing experiences; and (3) HIV testing and its role in the MSM community. These findings provide insight into HIV testing approaches and can be used to help strengthen HIV testing strategies for BLMSM in NYC.

      4. Leveraging differentiated HIV service delivery to expand tuberculosis preventive treatment: a call to actionexternal icon
        Rabkin M, Howard AA, Ehrenkranz P, Fernandez LG, Preko P, Singh V, Tomlinson HL, El-Sadr WM.
        Int J Tuberc Lung Dis. 2020 Feb 1;24(2):165-169.
        Tuberculosis (TB) is the leading cause of death among people living with human immunodeficiency virus (PLHIV), and sub-Saharan Africa has a particularly heavy burden of HIV-associated TB. Although effective TB preventive treatment (TPT) has been available for decades and shorter regimens are newly available in some settings, TPT coverage among PLHIV is suboptimal, leading to preventable illness and death. In 2018, the United Nations High-Level Meeting on Ending Tuberculosis called for ambitious new targets for TPT coverage among PLHIV and many countries in sub-Saharan Africa have redoubled their efforts to take TPT to scale. Importantly, however, this push to expand TPT among PLHIV is taking place in the context of a changing HIV treatment delivery landscape. Countries in sub-Saharan Africa are at the forefront of innovative changes in HIV program design, including a shift towards less-intensive differentiated service delivery (DSD) models for stable patients doing well on antiretroviral therapy. Understanding the opportunities and challenges that DSD presents for TB diagnosis, prevention and linkage to care among PLHIV will be critical to success.

      5. Short- and long-term pharmacologic measures of HIV pre-exposure prophylaxis use among high-risk men who have sex with men in HPTN 067/ADAPTexternal icon
        Velloza J, Bacchetti P, Hendrix CW, Murnane P, Hughes JP, Li M, Curlin ME, Holtz TH, Mannheimer S, Marzinke MA, Amico KR, Liu A, Piwowar-Manning E, Eshleman SH, Dye BJ, Gandhi M, Grant RM.
        J Acquir Immune Defic Syndr. 2019 Oct 1;82(2):149-158.
        BACKGROUND: The effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate-based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence. SETTING: We analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S. METHODS: After a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations. RESULTS: Among 350 participants (median age: 31 years, interquartile range: 25-38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non-daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r >/= 0.29) across visits. CONCLUSIONS: In HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.

      6. The impact of smoking on tuberculosis treatment outcomes: a meta-analysisexternal icon
        Wang EY, Arrazola RA, Mathema B, Ahluwalia IB, Mase SR.
        Int J Tuberc Lung Dis. 2020 Feb 1;24(2):170-175.
        BACKGROUND: Cigarette smoking contributes to tuberculosis (TB) epidemiology. However, limited evidence exists on how smoking impacts TB treatment outcomes such as treatment loss to follow-up and culture conversion.METHODS: This meta-analysis assessed current evidence of the impact of active cigarette smoking on TB treatment outcomes. PubMed, Scopus, Embase, and the Cochrane Library were searched for English-language articles published from database inception through 2017. Articles addressing active pulmonary TB and cigarette smoking were identified and data abstracted. Smokers were defined as those who smoked every day or some days at the time of interview/diagnosis. Non-smokers did not smoke at the time of interview/diagnosis. Unfavorable outcomes included any outcome other than cure or completion of TB treatment. Three different data sets were examined: 8 articles addressing unfavorable treatment outcomes, 9 analyzing only treatment loss to follow-up, and 5 addressing delayed smear or culture conversion. Studies that had <20 subjects or that addressed only populations with comorbidities were excluded.RESULTS: We identified 1030 studies; 21 studies fulfilled the inclusion/exclusion criteria. Smokers had greater odds of unfavorable outcomes (pooled odds ratio [pOR] 1.23, 95%CI 1.14-1.33), delayed smear or culture conversion (pOR 1.55, 95%CI 1.04-2.07), and treatment loss to follow-up (pOR 1.35, 95%CI 1.21-1.50).CONCLUSION: Cigarette smoking is associated with negative treatment results and delayed conversion to negative smear or culture, suggesting smoking is an important factor for consideration in TB elimination efforts.

    • Disease Reservoirs and Vectors
      1. Clinical presentation and serologic response during a rabies epizootic in captive common vampire bats (Desmodus rotundus)external icon
        Cardenas-Canales EM, Gigante CM, Greenberg L, Velasco-Villa A, Ellison JA, Satheshkumar PS, Medina-Magues LG, Griesser R, Falendysz E, Amezcua I, Osorio JE, Rocke TE.
        Trop Med Infect Dis. 2020 Mar 1;5(1).
        We report mortality events in a group of 123 common vampire bats (Desmodus rotundus) captured in Mexico and housed for a rabies vaccine efficacy study in Madison, Wisconsin. Bat mortalities occurred in Mexico and Wisconsin, but rabies cases reported herein are only those that occurred after arrival in Madison (n = 15). Bats were confirmed positive for rabies virus (RABV) by the direct fluorescent antibody test. In accordance with previous reports, we observed long incubation periods (more than 100 days), variability in clinical signs prior to death, excretion of virus in saliva, and changes in rabies neutralizing antibody (rVNA) titers post-infection. We observed that the furious form of rabies (aggression, hyper-salivation, and hyper-excitability) manifested in three bats, which has not been reported in vampire bat studies since 1936. RABV was detected in saliva of 5/9 bats, 2-5 days prior to death, but was not detected in four of those bats that had been vaccinated shortly after exposure. Bats from different capture sites were involved in two separate outbreaks, and phylogenetic analysis revealed differences in the glycoprotein gene sequences of RABV isolated from each event, indicating that two different lineages were circulating separately during capture at each site.

      2. Detection of Rickettsia asembonensis in fleas (Siphonaptera: Pulicidae, Ceratophyllidae) collected in five counties in Georgia, United Statesexternal icon
        Eremeeva ME, Capps D, McBride CL, Williams-Newkirk AJ, Dasch GA, Salzer JS, Beati L, Durden LA.
        J Med Entomol. 2020 Mar 3.
        We conducted a molecular survey of Rickettsia in fleas collected from opossums, road-killed and live-trapped in peridomestic and rural settings, state parks, and from pet cats and dogs in Georgia, United States during 1992-2014. The cat flea, Ctenocephalides felis (Bouche) was the predominant species collected from cats and among the archival specimens from opossums found in peridomestic settings. Polygenis gwyni (Fox) was more prevalent on opossums and a single cotton rat trapped in sylvatic settings. Trapped animals were infested infrequently with the squirrel flea, Orchopeas howardi (Baker) and C. felis. TaqMan assays targeting the BioB gene of Rickettsia felis and the OmpB gene of Rickettsia typhi were used to test 291 flea DNAs for Rickettsia. A subset of 53 C. felis collected from a cat in 2011 was tested in 18 pools which were all bioB TaqMan positive (34% minimum infection prevalence). Of 238 fleas tested individually, 140 (58.8%, 95% confidence interval [CI]: 52.5-64.9%) DNAs were bioB positive. Detection of bioB was more prevalent in individual C. felis (91%) compared to P. gwyni (13.4%). Twenty-one (7.2%) were ompB TaqMan positive, including 18 C. felis (9.5%) and 3 P. gwyni (3.2%). Most of these fleas were also positive with bioB TaqMan; however, sequencing of gltA amplicons detected only DNA of Rickettsia asembonensis. Furthermore, only the R. asembonensis genotype was identified based on NlaIV restriction analysis of a larger ompB fragment. These findings contribute to understanding the diversity of Rickettsia associated with fleas in Georgia and emphasize the need for development of more specific molecular tools for detection and field research on rickettsial pathogens.

      3. Risk modeling of bat rabies in the Caribbean Islandsexternal icon
        Morgan CN, Wallace RM, Vokaty A, Seetahal JF, Nakazawa YJ.
        Trop Med Infect Dis. 2020 Mar 1;5(1).
        Rabies surveillance and control measures vary significantly between Caribbean islands. The Centers for Disease Control and Prevention currently recommends certain groups of U.S. travelers to any Caribbean island receive pre-exposure rabies immunization. However, most islands self-declare as "rabies free", and have never publicly released data to support rabies-free claims. We used the Analytic Hierarchy Process to create pairwise comparison values among five risk factors determined by subject matter experts. Risk factor weights were calculated and used in a geospatial analysis to calculate a risk value for each island nation (higher values indicate higher risk). Risk values ranged from 8.73 (Trinidad) to 1.57 (The Bahamas, Turks and Caicos Islands). All four countries that have documented occurrences of laboratory confirmed rabid bats were ranked highest (Trinidad and Tobago, Grenada, Cuba, Dominican Republic), as well as Haiti. The top five highest risk countries that currently have no reports of bat rabies include St. Vincent and the Grenadines, Jamaica, Puerto Rico, the Cayman Islands, and Dominica. This study reviews the inter-island movement potential of bats, designates areas of high risk for bat-associated rabies within the Caribbean islands, and demonstrates a need for further surveillance efforts in bat populations within islands that self-declare as rabies free.

    • Environmental Health
      1. Air pollution, neighborhood deprivation, and autism spectrum disorder in the Study to Explore Early Developmentexternal icon
        McGuinn LA, Windham GC, Messer LC, Di Q, Schwartz J, Croen LA, Moody EJ, Rappold AG, Richardson DB, Neas LM, Gammon MD, Schieve LA, Daniels JL.
        Environ Epidemiol. 2019 ;3(5).
        Background: To examine whether neighborhood deprivation modifies the association between early life air pollution exposure and autism spectrum disorder (ASD), we used resources from a multisite case-control study, the Study to Explore Early Development. Method(s): Cases were 674 children with confirmed ASD born in 2003-2006; controls were 855 randomly sampled children born during the same time period and residents of the same geographic areas as cases. Air pollution was assessed by roadway proximity and particulate matter <2.5 micro m (PM<sup>2.5</sup>) exposure during pregnancy and first year of life. To characterize neighborhood deprivation, an index was created based on eight census tract-level socioeconomic status-related parameters. The continuous index was categorized into tertiles, representing low, moderate, and high deprivation. Logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Result(s): Neighborhood deprivation modified (P<sup>for interaction</sup> = 0.08) the association between PM<sup>2.5</sup> exposure during the first year of life and ASD, with a stronger association for those living in high (OR = 2.42, 95% CI = 1.20, 4.86) rather than moderate (OR=1.21, 95% CI = 0.67, 2.17) or low (OR=1.46, 95% CI = 0.80, 2.65) deprivation neighborhoods. Departure from additivity or multiplicativity was not observed for roadway proximity or exposures during pregnancy. Conclusion(s): These results provide suggestive evidence of interaction between neighborhood deprivation and PM<sup>2.5</sup> exposure during the first year of life in association with ASD.

      2. Organophosphate esters in a cohort of pregnant women: Variability and predictors of exposureexternal icon
        Percy Z, Vuong AM, Ospina M, Calafat AM, La Guardia MJ, Xu Y, Hale RC, Dietrich KN, Xie C, Lanphear BP, Braun JM, Cecil KM, Yolton K, Chen A.
        Environ Res. 2020 Feb 13;184:109255.
        Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks' gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5-2.3 mug/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75-0.99 mug/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72-0.97 mug/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25-0.28 mug/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (rs: 0.23-0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16-0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility.

    • Epidemiology and Surveillance
      1. Konzo outbreak in the Western Province of Zambiaexternal icon
        Siddiqi OK, Kapina M, Kumar R, Ngomah Moraes A, Kabwe P, Mazaba ML, Hachaambwa L, Ng'uni NM, Chikoti PC, Morel-Espinosa M, Jarrett JM, Baggett HC, Chizema-Kawesha E.
        Neurology. 2020 Mar 3.
        OBJECTIVE: To identify the etiology of an outbreak of spastic paraparesis among women and children in the Western Province of Zambia suspected to be konzo. METHODS: We conducted an outbreak investigation of individuals from Mongu District, Western Province, Zambia, who previously developed lower extremity weakness. Cases were classified with the World Health Organization definition of konzo. Active case finding was conducted through door-to-door evaluation in affected villages and sensitization at local health clinics. Demographic, medical, and dietary history was used to identify common exposures in all cases. Urine and blood specimens were taken to evaluate for konzo and alternative etiologies. RESULTS: We identified 32 cases of konzo exclusively affecting children 6 to 14 years of age and predominantly females >14 years of age. Fourteen of 15 (93%) cases >/=15 years of age were female, 11 (73%) of whom were breastfeeding at the time of symptom onset. Cassava was the most commonly consumed food (median [range] 14 [4-21] times per week), while protein-rich foods were consumed <1 time per week for all cases. Of the 30 patients providing urine specimens, median thiocyanate level was 281 (interquartile range 149-522) mumol/L, and 73% of urine samples had thiocyanate levels >136 mumol/L, the 95th percentile of the US population in 2013 to 2014. CONCLUSION: This investigation revealed the first documented cases of konzo in Zambia, occurring in poor communities with diets high in cassava and low in protein, consistent with previous descriptions from neighboring countries.

    • Healthcare Associated Infections
      1. Exploration of risk factors for ceftriaxone resistance in invasive non-typhoidal Salmonella infections in western Kenyaexternal icon
        Luvsansharav UO, Wakhungu J, Grass J, Oneko M, Nguyen V, Bigogo G, Ogola E, Audi A, Onyango D, Hamel MJ, Montgomery JM, Fields PI, Mahon BE.
        PLoS One. 2020 ;15(3):e0229581.
        Multidrug-resistant non-typhoidal Salmonella (NTS) infection has emerged as a prominent cause of invasive infections in Africa. We investigated the prevalence of ceftriaxone-resistant invasive NTS infections, conducted exploratory analysis of risk factors for resistance, and described antimicrobial use in western Kenya. We conducted a secondary analysis of existing laboratory, epidemiology, and clinical data from three independent projects, a malaria vaccine trial, a central nervous system (CNS) study, and the International Emerging Infections Program morbidity surveillance (surveillance program) during 2009-2014. We calculated odds ratios (OR) with 95% confidence intervals (CI) for ceftriaxone-resistant NTS infections compared with ceftriaxone-susceptible infections. We surveyed hospitals, pharmacies, and animal drug retailers about the availability and use of antimicrobials. In total, 286 invasive NTS infections were identified in the three projects; 43 NTS isolates were ceftriaxone-resistant. The absolute prevalence of ceftriaxone resistance varied among these methodologically diverse projects, with 18% (16/90) of isolates resistant to ceftriaxone in the vaccine trial, 89% (16/18) in the CNS study, and 6% (11/178) in the surveillance program. Invasive ceftriaxone-resistant infections increased over time. Most ceftriaxone-resistant isolates were co-resistant to multiple other antimicrobials. Having an HIV-positive mother (OR = 3.7; CI = 1.2-11.4) and taking trimethoprim-sulfamethoxazole for the current illness (OR = 9.6, CI = 1.2-78.9) were significantly associated with acquiring ceftriaxone-resistant invasive NTS infection. Ceftriaxone and other antibiotics were widely prescribed; multiple issues related to prescription practices and misuse were identified. In summary, ceftriaxone-resistant invasive NTS infection is increasing and limiting treatment options for serious infections. Efforts are ongoing to address the urgent need for improved microbiologic diagnostic capacity and an antimicrobial surveillance system in Kenya.

      2. INTRODUCTION: The prevalence of azole resistance in C. parapsilosis is very low in most parts of the world. However, South Africa has reported an exceptionally high prevalence of azole resistance in C. parapsilosis strains isolated from candidaemia cases. We aimed to determine the possible molecular mechanisms of fluconazole resistance in C. parapsilosis isolates obtained through surveillance at a large neonatal unit at a South African academic hospital. METHODS: We sequenced the ERG11 and MRR1 genes of C. parapsilosis isolates recovered from cases of neonatal candidemia, followed by microsatellite genotyping. A total of 73 isolates with antifungal susceptibility results were analysed. RESULTS: Of these, 57 (78%) were resistant, 11 (15%) susceptible-dose-dependent and 5 (7%) susceptible. The most commonly identified amino acid substitution within the ERG11 gene was Y132F in 68% (39/57) of fluconazole-resistant isolates and none in susceptible isolates. Three amino acid substitutions (R405K, G583R, and A619V) and 1 nucleotide deletion at position 1331 were identified within MRR1 gene in 19 (26%) isolates. Microsatellite genotyping grouped isolates into four clusters (50 isolates). Cluster 1 accounted for 23% (17/73) of all cases, cluster 2 for 22% (16/73), cluster 3 for 14% (10/73) and cluster 4 for 10% (7/73). We found an association between cluster type and fluconazole resistance (p-value=0.004). Isolates harboring the Y132F substitution were more likely to belong to a cluster than non-Y132F isolates. CONCLUSION: Fluconazole resistance in C. parapsilosis strains from a single South African neonatal unit was associated with cluster type and predominantly driven by Y123F amino acid substitutions in the ERG11 gene.

    • Immunity and Immunization
      1. Evaluating partial series childhood vaccination services in a mobile clinic settingexternal icon
        Chen W, Misra SM, Zhou F, Sahni LC, Boom JA, Messonnier M.
        Clin Pediatr (Phila). 2020 Feb 28:9922820908586.
        This study aims to evaluate the cost-benefit of vaccination services, mostly partial series administration, provided by a mobile clinic program (MCP) in Houston for children of transient and low-income families. The study included 469 patients who visited the mobile clinics on regular service days in 2 study periods in 2014 and 836 patients who attended vaccination events in the summer of 2014. The benefit of partial series vaccination was estimated based on vaccine efficacy/effectiveness data. Our conservative cost-benefit estimates show that, compared with office-based settings, every dollar spent on vaccination by the MCP would result in $0.9 societal cost averted as an incremental benefit in regular service days and $3.7 during vaccination-only events. To further improve the cost-benefit of vaccination services in the MCP, decision-makers and stakeholders may consider improving work efficiency during regular service days or hosting more vaccination events.

      2. Meningococcal carriage in young adults six years after meningococcal C conjugate (MCC) vaccine catch-up campaign in Salvador, Brazilexternal icon
        Ferreira VM, Ferreira IE, Chang HY, Nunes A, Topaz N, Pimentel ER, Moura A, Ribeiro GS, Feitosa CA, Reis MG, Wang X, Campos LC.
        Vaccine. 2020 Feb 27.
        Meningococcal carriage studies are important to improve the knowledge of disease epidemiology as well as to support appropriate vaccination strategies. We conducted a cross-sectional study to determine the prevalence and genotypic characteristics of meningococci collected from young adults in Salvador, Brazil six years after a meningococcal C conjugate vaccine catch-up campaign. From August through November 2016, oropharyngeal swabs were collected from 407 students aged 1824 years attending a private college in Salvador, Brazil. Neisseria meningitidis was identified by standard microbiology methods and real time PCR. Genetic characteristics of meningococci were assessed by rt-PCR and/or whole genome sequencing. We also investigated potential factors associated with carriage. N. meningitidis was detectable in 50 students, 39 by both culture and rt-PCR, 7 by culture alone and 4 by rt-PCR alone, resulting in an overall meningococcal carriage prevalence of 12.3% (50/407). Carriage was independently associated with male sex (adjusted PR: 1.97; 95% CI: 1.12-3.46; p = 0.018) and attending bars or parties at least once per month (aPR: 3.31; 95% CI: 1.49-7.38; p = 0.003). Molecular tests identified 92% (46/50) N. meningitidis as non-groupable, of which 63% (29/46) had the capsule null genotype; 14 NG isolates contained disrupted capsule backbones and belonged to the following genogroups: 7 B, 3 Z, 3 E and 1 W. One isolate belonged to genogroup C tested only by PCR; 3 isolates contained a complete B capsule backbones, 2 of which were determined to be NG by slide agglutination serogrouping. While most meningococcal carriage isolates were non-groupable, there was a high degree of genetic diversity present in the collection, as evidenced by 25 unique STs being detected. The carriage prevalence of meningococcal serogroup C was low among young adults. Continuous vaccination is important to maintain reduced meningococcal carriage and transmission, inducing herd protection.

      3. OBJECTIVE: To evaluate the ability of different types of vaccine storage units to maintain appropriate temperatures for the storage of vaccines and to characterize deviations from recommended temperatures. DATA SOURCES: Continuous temperature monitoring devices, or digital data loggers, from vaccine providers who participated in a continuous temperature monitoring pilot project. STUDY DESIGN: We computed descriptive statistics on the percentage of runtime with an out-of-range temperature, or excursion, for different storage unit types (freezers and refrigerators) and for different storage unit grades (household-grade combination, household-grade stand alone, and purpose-built or pharmaceutical grade). We developed frequency histograms for the percentage of storage unit runtime outside of the normal range. We plotted the duration and temperature extrema for identified excursions. Analyses were stratified by storage unit type and grade. RESULTS: Household-grade combination units underperformed relative to household-grade stand-alone and purpose-built units. Among refrigerators, household-grade combination units operated in the normal temperature range an average of 98.9% of their observed runtime, which was lower than 99.4% (p value = 0.038) for household-grade stand-alone and 99.9% (p value < 0.001) for purpose-built units. Among freezers, household-grade combination units operated in the normal temperature range an average of 95.0% of their observed runtime, which was lower than 99.3% (p value < 0.001) for household-grade stand-alone units and 99.7% (p value < 0.001) for purpose-built units. CONCLUSION: These findings, in particular the underperformance of household-grade combination units relative to household-grade stand-alone and purpose-built units, support current CDC recommendations to avoid the use of household-grade combination storage units when possible.

    • Laboratory Sciences
      1. Experimental infection of Egyptian rousette bats (Rousettus aegyptiacus) with Sosuga virus demonstrates potential transmission routes for a bat-borne human pathogenic paramyxovirusexternal icon
        Amman BR, Schuh AJ, Sealy TK, Spengler JR, Welch SR, Kirejczyk SG, Albarino CG, Nichol ST, Towner JS.
        PLoS Negl Trop Dis. 2020 Mar 2;14(3):e0008092.
        In August 2012, a wildlife biologist became severely ill after becoming infected with a novel paramyxovirus, termed Sosuga virus. In the weeks prior to illness, the patient worked with multiple species of bats in South Sudan and Uganda, including Egyptian rousette bats (ERBs: Rousettus aegyptiacus). A follow-up study of Ugandan bats found multiple wild-caught ERBs to test positive for SOSV in liver and spleen. To determine the competency of these bats to act as a natural reservoir host for SOSV capable of infecting humans, captive-bred ERBs were inoculated with a recombinant SOSV, representative of the patient's virus sequence. The bats were inoculated subcutaneously, sampled daily (blood, urine, fecal, oral and rectal swabs) and serially euthanized at predetermined time points. All inoculated bats became infected with SOSV in multiple tissues and blood, urine, oral, rectal and fecal swabs tested positive for SOSV RNA. No evidence of overt morbidity or mortality were observed in infected ERBs, although histopathological examination showed subclinical disease in a subset of tissues. Importantly, SOSV was isolated from oral/rectal swabs, urine and feces, demonstrating shedding of infectious virus concomitant with systemic infection. All bats euthanized at 21 days post-inoculation (DPI) seroconverted to SOSV between 16 and 21 DPI. These results are consistent with ERBs being competent reservoir hosts for SOSV with spillover potential to humans.

      2. Citrullination alters the antiviral and immunomodulatory activities of the human cathelicidin LL-37 during rhinovirus infectionexternal icon
        Casanova V, Sousa FH, Shakamuri P, Svoboda P, Buch C, D'Acremont M, Christophorou MA, Pohl J, Stevens C, Barlow PG.
        Front Immunol. 2020 ;11:85.
        Human rhinoviruses (HRV) are the most common cause of viral respiratory tract infections. While normally mild and self-limiting in healthy adults, HRV infections are associated with bronchiolitis in infants, pneumonia in immunocompromised patients, and exacerbations of asthma and COPD. The human cathelicidin LL-37 is a host defense peptide (HDP) with broad immunomodulatory and antimicrobial activities that has direct antiviral effects against HRV. However, LL-37 is known to be susceptible to the enzymatic activity of peptidyl arginine deiminases (PAD), and exposure of the peptide to these enzymes results in the conversion of positively charged arginines to neutral citrullines (citrullination). Here, we demonstrate that citrullination of LL-37 reduced its direct antiviral activity against HRV. Furthermore, while the anti-rhinovirus activity of LL-37 results in dampened epithelial cell inflammatory responses, citrullination of the peptide, and a loss in antiviral activity, ameliorates this effect. This study also demonstrates that HRV infection upregulates PAD2 protein expression, and increases levels of protein citrullination, including histone H3, in human bronchial epithelial cells. Increased PADI gene expression and HDP citrullination during infection may represent a novel viral evasion mechanism, likely applicable to a wide range of pathogens, and should therefore be considered in the design of therapeutic peptide derivatives.

      3. Cabotegravir long-acting protects macaques against repeated penile SHIV exposuresexternal icon
        Dobard C, Makarova N, Nishiura K, Dinh C, Holder A, Sterling M, Lipscomb J, Mitchell J, Deyounks F, Garber D, Khalil G, Spreen W, Heneine W, Garcia-Lerma JG.
        J Infect Dis. 2020 Mar 4.
        We used a novel penile simian HIV (SHIV) transmission model to investigate if cabotegravir long-acting (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once-weekly for 12 weeks. Of these, six received human-equivalent doses of CAB LA, six received oral FTC/TDF, and 10 were untreated. The efficacy of CAB LA was high (94.4% [95%CI=58.2%-99.3%]) and similar to that seen with oral FTC/TDF (94.0% [95%CI=55.1%-99.2%]). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA PrEP to heterosexual men.

      4. Hormonal profiles of menstrual bleeding patterns during the luteal-follicular transitionexternal icon
        Jacobson MH, Howards PP, Kesner JS, Meadows JW, Dominguez CE, Spencer JB, Darrow LA, Terrell ML, Marcus M.
        J Clin Endocrinol Metab. 2020 Mar 2.
        CONTEXT: Menstrual cycle function is determined by a complex endocrine axis that controls the ovaries and endometrium. While the late luteal phase is characterized by declining progesterone and estrogen, how these hormonal profiles relate to menstrual bleeding patterns is not well understood. OBJECTIVE: Characterize associations between luteal phase hormonal profiles and subsequent menstrual bleeding patterns; specifically spotting before bleeding. DESIGN, SETTING, AND PARTICIPANTS: We examined creatinine-adjusted urinary estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) levels in relation to spotting in 116 premenopausal women (ages 20-47) who kept daily menstrual diaries and collected first morning urine samples for >/=2 consecutive cycles or 1 luteal-follicular transition (n=283 transitions). We used linear mixed models to estimate associations between luteal phase hormone levels and spotting before bleeding. MAIN OUTCOME MEASURE(S) AND RESULTS: Transitions with >/=1 days of spotting before menstrual bleeding (n=118) had greater luteal phase Pd3G levels vs. non-spotting transitions (n=165). Differences in Pd3G between spotting and non-spotting transitions were largest at menses onset (34.8%, 95% confidence interval: 18.9%, 52.7%). Pd3G levels for spotting transitions dropped to similar levels as non-spotting transitions an average of 1 day later, which aligned with the first day of bleeding for transitions with contiguous spotting. Spotting transitions were preceded by slower rates of Pd3G decline than non-spotting transitions, whereas E13G declines were similar. CONCLUSIONS: Self-reported bleeding patterns may provide insight into luteal phase Pd3G levels. First bleed appears to be the best choice for defining the end of the luteal phase and achieving hormonal consistency across transitions.

      5. Enhanced morphological transformation of human lung epithelial cells by continuous exposure to cellulose nanocrystalsexternal icon
        Kisin ER, Yanamala N, Rodin D, Menas A, Farcas M, Russo M, Guppi S, Khaliullin TO, Iavicoli I, Harper M, Star A, Kagan VE, Shvedova AA.
        Chemosphere. 2020 Feb 13;250:126170.
        Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.

      6. Capture and detection of Plasmodium vivax lactate dehydrogenase in a bead-based multiplex immunoassayexternal icon
        Rogier E, Nace D, Ljolje D, Lucchi NW, Udhayakumar V, Aidoo M.
        Am J Trop Med Hyg. 2020 Mar 2.
        Laboratory detection of malaria antigens has proved valuable for research and epidemiological purposes. We recently developed a bead-based multiplex antigen assay for pan-Plasmodium and Plasmodium falciparum targets. Here, we report integration of a Plasmodium vivax-specific target to this multiplex panel: P. vivax lactate dehydrogenase (PvLDH). Within the multiplex panel, assay signal for purified PvLDH antigen titrated into the single-digit picogram range. Against a panel of PCR-confirmed samples from acute P. vivax infections (n = 36), sensitivity was 91.7% in using PvLDH detection for identifying the presence of parasites. Specificity against a panel of persons with no Plasmodium infection (n = 44) was 100%, and specificity against a panel of PCR-confirmed P. falciparum, Plasmodium malariae, or Plasmodium ovale infections (n = 164) was 90.2%. Addition of this PvLDH capture and detection system into the multiplex antigen panel will now allow for sensitive screening for species identification of both P. falciparum and P. vivax in the laboratory.

      7. Inhibition of Nipah virus by defective interfering particlesexternal icon
        Welch SR, Tilston NL, Lo MK, Whitmer SL, Harmon JR, Scholte FE, Spengler JR, Duprex WP, Nichol ST, Spiropoulou CF.
        J Infect Dis. 2020 Feb 28.
        The error-prone nature of ribonucleic acid (RNA)-dependent RNA polymerases drives the diversity of RNA virus populations. Arising within this diversity is a subset of defective viral genomes that retain replication competency, termed defective interfering (DI) genomes. These defects are caused by aberrant viral polymerase reinitiation on the same viral RNA template (deletion DI species) or the nascent RNA strand (copyback DI species). Defective interfering genomes have previously been shown to alter the dynamics of a viral population by interfering with normal virus replication and/or by stimulating the innate immune response. In this study, we investigated the ability of artificially produced DI genomes to inhibit Nipah virus (NiV), a highly pathogenic biosafety level 4 paramyxovirus. High multiplicity of infection passaging of both NiV clinical isolates and recombinant NiV in Vero cells generated an extensive DI population from which individual DIs were identified using next-generation sequencing techniques. Assays were established to generate and purify both naturally occurring and in silico-designed DIs as fully encapsidated, infectious virus-like particles termed defective interfering particles (DIPs). We demonstrate that several of these NiV DIP candidates reduced NiV titers by up to 4 logs in vitro. These data represent a proof-of-principle that a therapeutic application of DIPs to combat NiV infections may be an alternative source of antiviral control for this disease.

    • Medicine
      1. Parvovirus B19 infection in sickle cell disease: An analysis from the Centers for Disease Control haemoglobinopathy blood surveillance projectexternal icon
        Majumdar S, Bean CJ, De Staercke C, Bost J, Nickel R, Coates T, Campbell A, Thompson A.
        Transfus Med. 2020 Mar 4.
        OBJECTIVE: In the multicentre Haemoglobinopathy Blood Surveillance Project, to evaluate the seroprevalence of parvovirus B19 and DNA viral load in sickle cell disease (SCD). BACKGROUND: Although the epidemiology of parvovirus B19 seropositivity in SCD has been well documented, there are few studies that have assessed possible persistent parvovirus DNAemia and associated risk factors including blood transfusion. METHODS: A qualitative analysis of parvovirus B19 serology using ELISA and quantitative parvovirus B19 DNA by RT-PCR was performed in patients with SCD. RESULTS: Of 322 patients, 113 (35%) were parvovirus IgG positive and 119 (37%) were IgM positive at enrolment. The prevalence of IgG positivity increased with age. 71/322 (22%) were parvovirus DNA positive at enrolment with a mean viral load of 15 227 +/- 55 227 SD. (range 72-329 238 IU/mL). Patients who were positive for parvovirus B19 DNA received a significantly higher red blood cell transfusion volume in the prior year compared to patients who were negative (mean RBC volume = 8310 mL vs 5435 mL, respectively; P = .0073). Seventy-seven patients had follow-up testing approximately 1 year after enrolment and 11/28 (39%) patients had persistently positive IgM. CONCLUSION: Further studies are needed to better understand the natural history of parvovirus B19 infection in SCD especially in relation to RBC transfusion as a risk factor, as well as disease outcome and severity.

    • Nutritional Sciences
      1. OBJECTIVE: To evaluate the impact of an infant, young child feeding practices-small-quantity lipid nutrient supplements (SQ-LNS) intervention on child development scores in children aged 6-18 months in the Katanga Province, Democratic Republic of Congo (DRC). STUDY DESIGN: We analyzed data of 2595 children from 2 health zones in a quasi-experimental design with preimplementation and postimplementation surveys to evaluate program impact on child development scores. Standard care was received in the comparison health zone and the intervention health zone received standard care plus enhanced infant, young child feeding practices with a monthly supply of 28 SQ-LNS sachets for up to 1 year. Program exposure and communication and motor domains of the Ages and Stages questionnaire were collected to assess changes in child development scores. A quasi-intent-to-treat and adjusted difference-in-difference analyses were used to quantify impact of the enhanced compared with the standard package. RESULTS: In adjusted models contrasting endline with baseline, there was a greater relative increase in proportion of children with normal communication (difference-in-difference, +13.7% [95%CI, 7.9-19.6; P < .001] and gross motor scores, +7.4% [95% CI: 1.3-13.5; P < .001]) in the intervention vs comparison health zones. Further, in separate analyses among children of intervention health zone at endline, each additional SQ-LNS distribution was associated with +0.09 (95% CI, 0.03-0.16) z-score unit increase in gross motor scores (P < .01). CONCLUSIONS: The integrated infant, young child feeding practice-SQ-LNS intervention was positively associated with larger relative improvements in measures of child communication and motor development in the Katanga province of DRC.

    • Occupational Safety and Health
      1. Associations of sickness absence for pain in the low back, neck and shoulders with wider propensity to painexternal icon
        Coggon D, Ntani G, Walker-Bone K, Felli VE, Harari R, Barrero LH, Felknor SA, Rojas M, Cattrell A, Serra C, Bonzini M, Solidaki E, Merisalu E, Habib RR, Sadeghian F, Kadir MM, Wickremasinghe AR, Matsudaira K, Nyantumbu-Mkhize B, Kelsall HL, Harcombe H.
        Occup Environ Med. 2020 Feb 20.
        OBJECTIVES: To explore the association of sickness absence ascribed to pain at specific anatomical sites with wider propensity to musculoskeletal pain. METHODS: As part of the CUPID (Cultural and Psychosocial Influences on Disability) study, potential risk factors for sickness absence from musculoskeletal pain were determined for 11 922 participants from 45 occupational groups in 18 countries. After approximately 14 months, 9119 (78%) provided follow-up information about sickness in the past month because of musculoskeletal pain, including 8610 who were still in the same job. Associations with absence for pain at specific anatomical sites were assessed by logistic regression and summarised by ORs with 95% CIs. RESULTS: 861 participants (10%) reported absence from work because of musculoskeletal pain during the month before follow-up. After allowance for potential confounders, risk of absence ascribed entirely to low back pain (n=235) increased with the number of anatomical sites other than low back that had been reported as painful in the year before baseline (ORs 1.6 to 1.7 for >/=4 vs 0 painful sites). Similarly, associations with wider propensity to pain were observed for absence attributed entirely to pain in the neck (ORs up to 2.0) and shoulders (ORs up to 3.4). CONCLUSIONS: Sickness absence for pain at specific anatomical sites is importantly associated with wider propensity to pain, the determinants of which extend beyond established risk factors such as somatising tendency and low mood. Better understanding of why some individuals are generally more prone to musculoskeletal pain might point to useful opportunities for prevention.

    • Parasitic Diseases
      1. Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coastexternal icon
        Knudson A, Gonzalez-Casabianca F, Feged-Rivadeneira A, Pedreros MF, Aponte S, Olaya A, Castillo CF, Mancilla E, Piamba-Dorado A, Sanchez-Pedraza R, Salazar-Terreros MJ, Lucchi N, Udhayakumar V, Jacob C, Pance A, Carrasquilla M, Apraez G, Angel JA, Rayner JC, Corredor V.
        Sci Rep. 2020 Feb 28;10(1):3756.
        As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests.

      2. Cutaneous microsporidiosis in an immunosuppressed patientexternal icon
        Nadelman DA, Bradt AR, Qvarnstrom Y, Goldsmith CS, Zaki SR, Wang F, Smith EH, Fullen DR.
        J Cutan Pathol. 2020 Mar 3.
        Microsporidia are a group of obligate intracellular parasites that naturally infect domestic and wild animals. Human microsporidiosis is an increasingly recognized multisystem opportunistic infection. The clinical manifestations are diverse with diarrhea being the most common presenting symptom. We present a 52-year-old woman with a history of amyopathic dermatomyositis complicated by interstitial lung disease managed with mycophenolate mofetil and hydroxychloroquine who presented with a seven-month history of recurrent subcutaneous nodules as well as intermittent diarrhea and chronic sinusitis. A punch biopsy demonstrated superficial and deep lymphocytic and granulomatous dermatitis with focal necrosis. Tissue stains for microorganisms revealed oval 1-3 mum spores within the necrotic areas in multiple tissue stains. Additional studies at the Centers for Disease Control confirmed cutaneous microsporidiosis. This case is one of very few confirmed examples of cutaneous microsporidiosis reported in the literature. This article is protected by copyright. All rights reserved.

    • Reproductive Health
      1. OBJECTIVE: To evaluate the effectiveness of intracytoplasmic sperm injection (ICSI) in improving fertilization rates compared to conventional in vitro fertilization rates (IVF) among women aged >/=38 years with a non-male factor diagnosis. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women aged >/=38 years with a non-male factor diagnosis receiving IVF or ICSI. INTERVENTION(S): A systematic review of databases including PubMed and Embase was performed. Study protocol was registered at the International Prospective Register of Systematic Reviews. Studies were selected if they compared fertilization rates from ICSI with those from conventional IVF among women aged >/=38 years with a non-male factor infertility diagnosis. A random effects model was used. Meta-analysis of Observational Studies in Epidemiology guidelines were applied. MAIN OUTCOME MEASURE(S): Fertilization rate. RESULTS: Seven studies including 8796 retrieved oocytes (ICSI: 4,369; IVF: 4,427) with mean female age >/=38 years met the inclusion criteria. There was no significant difference in fertilization rates between ICSI and conventional IVF (relative risk [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; P = .8). Heterogeneity was observed between studies (I(2) = 58.2; P < .05). Heterogeneity was significant (I(2) = 57.1; P < .05) when cycles with prior fertilization failure were excluded; however, when analysis was restricted to poor responders (RR 1.01, 95% CI 0.97-1.05; P = .6), heterogeneity was no longer significant (I(2) = 0.0; P = .5). CONCLUSIONS: No difference was found in fertilization rates between conventional IVF and ICSI. Further studies are needed to assess the impact of ICSI in this population, controlling for other indications such as preimplantation genetic testing.

    • Substance Use and Abuse

      1. Electronic cigarette use during preconception and/or pregnancy: Prevalence, characteristics, and concurrent mental health conditionsexternal icon
        Rollins LG, Sokol NA, McCallum M, England L, Matteson K, Werner E, Stroud LR.
        J Womens Health (Larchmt). 2020 Feb 28.
        Background: Electronic cigarettes (e-cigarettes) are increasing in popularity in the United States. Prior prevalence estimates of e-cigarette use in pregnancy range from 1% to 15%. Materials and Methods: We assessed prevalence of e-cigarette and conventional cigarette use during preconception or pregnancy in a large sample of racially/ethnically diverse, low-income pregnant women via telephone survey (2015-2018) and compared sociodemographic characteristics and mental health conditions. Results: Of 1365 pregnant women surveyed, 54 (4.0%) reported e-cigarette use (regardless of other tobacco use), 372 (27.3%) reported conventional cigarette use without e-cigarette use (conventional cigarette use), and 939 (68.8%) reported no tobacco or nicotine replacement therapy (NRT) product use during the preconception period and/or pregnancy. Seventy-four percent of women using e-cigarettes reported also using conventional cigarettes. Women who used e-cigarettes were more likely to report high school education or greater, income <$30,000, White race, and non-Hispanic ethnicity than women who used conventional cigarettes. Women who used e-cigarettes were more likely than women who used conventional cigarettes or no tobacco/NRT to report symptoms of depression. Women who used e-cigarettes and women who used conventional cigarettes were more likely than women who used no tobacco/NRT to report a history of severe mental health conditions, alcohol use during pregnancy, and marijuana or other drug use during preconception. Conclusions: In this sample, 4% of women used e-cigarettes during preconception and/or pregnancy and most also used conventional cigarettes. Increased efforts by providers to screen for tobacco (including use of e-cigarette) and polysubstance use and to provide cessation services could improve outcomes of mothers and children.

    • Zoonotic and Vectorborne Diseases
      1. Challenges in predicting Lyme disease riskexternal icon
        Kugeler KJ, Eisen RJ.
        JAMA Netw Open. 2020 Mar 2;3(3):e200328.


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Page last reviewed: March 23, 2020, 12:00 AM