Issue 40, November 3, 2021

CDC Science Clips: Volume 13, Issue 40, November 3, 2021

This week, Science Clips is pleased to feature articles from the American Journal of Preventive Medicine supplement The Evidence Base for Initial Intervention Strategies for Ending the HIV Epidemic in the U.S.external icon


In the 40 years since the first reported cases of AIDS, there have been several critical successes, including identifying HIV as the causative agent; defining the sexual and injection drug use behaviors that lead to a high risk for HIV transmission or acquisition; developing HIV antibody and nucleic acid tests; and developing and delivering medications to effectively treat HIV infection. More recently, clinician-delivered interventions were proven effective, including treatment to suppress HIV to levels that don’t permit sexual transmission and antiretroviral pre-exposure prophylaxis (PrEP) for persons without HIV if they are exposed to the virus. Use of all these interventions can markedly reduce HIV acquisition and transmission in the U.S.  Diagnosis of all persons with HIV to provide them with effective treatment, provision of PrEP to reduce sexual HIV acquisition and clean syringe access to reduce injection related HIV acquisition, and identifying and responding to clusters of rapid HIV spread together form the basis for a new federal initiative: Ending the HIV Epidemic (EHE) in the U.S. that takes an intensified all of government approach to reduce the number of Americans acquiring HIV infection by 75% by 2025 and by 90% by 2030.

To assist local and state Health Departments serving as the community’s primary mechanism for implementing critical HIV prevention programs, it is critical to share the evidence base for selecting, implementing, and disseminating interventions and strategies proven to be effective and feasible. This journal supplement includes both state of the science articles and best practice articles describing effective intervention strategies conducted by Local Health Departments before the EHE initiative began, for which an evaluation further supports the dissemination of the approach. The content of this supplement is intended to promote the ongoing sharing of lessons learned as Health Departments innovate, implement, and revise program efforts on the basis of an evolving evidence base to achieve EHE goals.

Thanks to Dawn K. Smith, MD MS MPH of CDC’s National Center for HIV, Viral Hepatitis, STD & TB Prevention for her assistance with this feature.


  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • The Evidence Base for Initial Intervention Strategies for Ending the HIV Epidemic in the US
      1. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV acquisition and is a critical tool in the Ending the HIV Epidemic in the U.S. initiative. However, major racial and ethnic disparities across the pre-exposure prophylaxis continuum, secondary to structural inequities and systemic racism, threaten progress. Many barriers, operating at the individual, network, healthcare, and structural levels, impede PrEP access and uptake within Black and Hispanic/Latino communities. This review provides an overview of those barriers and the innovative and collaborative solutions that health departments, healthcare organizations, and community partners have implemented to increase PrEP provision and uptake among disproportionately affected communities. Promising strategies at the individual and network levels focus on increasing patient support throughout the PrEP continuum, positioning and training community members to expand knowledge of and interest in PrEP, and leveraging mobile technologies to support PrEP uptake. Healthcare-level solutions include expanding the venues and types of healthcare professionals that can provide PrEP, and structural- and policy-level options focus on financial assistance programs and health insurance expansion. Key research gaps include demonstrating that pilot studies and interventions remain effective at scale and across varied contexts. Although the last 2 decades have provided effective tools to end the HIV epidemic, realizing this vision for the U.S. will require addressing persistent and pervasive HIV-related disparities in Black and Hispanic/Latino communities. Federal, state, and local partners should expand efforts to address longstanding health and structural inequities and partner with disproportionately affected communities to rapidly expand PrEP scale-up.

      2. Syringe Services Programs' Role in Ending the HIV Epidemic in the U.S.: Why We Cannot Do It Without Themexternal icon
        Broz D, Carnes N, Chapin-Bardales J, Des Jarlais DC, Handanagic S, Jones CM, McClung RP, Asher AK.
        Am J Prev Med. 2021 Nov;61(5s1):S118-s129.
        Diagnoses of HIV among people who inject drugs have increased in the U.S. during 2014-2018 for the first time in 2 decades, and multiple HIV outbreaks have been detected among people who inject drugs since 2015. These epidemiologic trends pose a significant concern for achieving goals of the federal initiative for Ending the HIV Epidemic in the U.S. Syringe services programs are cost effective, safe, and highly effective in reducing HIV transmission and are an essential component of a comprehensive, integrated approach to addressing these concerns. Yet, geographic coverage of these programs remains limited in the U.S., and many jurisdictions continue to have laws and policies that limit or disallow syringe services programs. An in-depth literature review was conducted on the role of syringe services programs in the Ending the HIV Epidemic initiative. Empirical and model-based evidence consistently shows that syringe services programs have the highest impact in HIV prevention when combined with access to medications for substance use disorder and antiretroviral therapy. Their effectiveness is further maximized when they provide services without restrictions and include proven and innovative strategies to expand access to harm-reduction and clinical services (e.g., peer outreach, telehealth). Increasing geographic and service coverage of syringe services programs requires strong and sustainable policy, funding, and community support and will need to address new challenges related to the COVID-19 pandemic. Syringe services programs have a key role in all 4 Ending the HIV Epidemic initiative strategies-Prevent, Diagnose, Treat, and Respond-and thus are instrumental to its success in preventing disease and saving lives.

      3. HIV Testing Strategies for Health Departments to End the Epidemic in the U.Sexternal icon
        Delaney KP, DiNenno EA.
        Am J Prev Med. 2021 Nov;61(5s1):S6-s15.
        An important goal of the Ending the HIV Epidemic in the U.S. initiative is the timely diagnosis of all people with HIV as early as possible after infection. To end the HIV epidemic, health departments were encouraged to propose new and innovative HIV testing strategies and improve the reach of existing programs. These activities were divided into 3 core strategies: expansion of routine screening in healthcare settings, locally tailored HIV testing initiatives in nonhealthcare settings, and specific efforts to increase the frequency of testing for individuals with increased potential for acquiring HIV. Because HIV testing is such a crucial part of the core activities of the Centers for Disease Control and Prevention's HIV prevention programs, there are many examples of evidence-based programs and best practices for HIV testing in both clinical and nonclinical settings. This article reviews the evidence base for these strategies and some of the activities proposed under the Diagnose pillar to achieve the goal of diagnosing all HIV infections as early as possible. All other Ending the HIV Epidemic in the U.S. activities start with an awareness of HIV status, which is actually the indicator for which most health departments are closest to the proposed targets. There are both proven and emerging approaches to increasing HIV screening and increasing the frequency of HIV screening available. The Ending the HIV Epidemic in the U.S. initiative provides the motivation, the resources, and a coordinated plan to bring them to scale.

      4. Costs and Consequences of Eliminating a Routine, Point-Of-Care HIV Screening Program in a High-Prevalence Jailexternal icon
        Hutchinson AB, MacGowan RJ, Margolis AD, Adee MG, Wen W, Bowden CJ, Spaulding AC.
        Am J Prev Med. 2021 Nov;61(5s1):S32-s38.
        INTRODUCTION: This study aims to assess the public health impact of eliminating a longstanding routine HIV screening program and replacing it with targeted testing. In addition, costs, outcomes, and cost effectiveness of routine screening are compared with those of targeted testing in the Fulton County Jail, Atlanta, Georgia. METHODS: A published mathematical model was used to assess the cost effectiveness and public health impact of routine screening (March 2013-February 2014) compared with those of targeted testing (January 2018-December 2018) from a health system perspective. Costs, outcomes, and other model inputs were derived from the testing programs and the published literature, and the cost effectiveness analysis was conducted from 2019 to 2020. RESULTS: Routine screening identified 74 more new HIV infections over 1 year than targeted testing, resulting in an estimated 10 HIV transmissions averted and 45 quality-adjusted life-years saved, and was cost saving. The missed opportunity to diagnose infections because routine screening was eliminated resulted in an estimated 8.4 additional HIV transmissions and $3.7 million in additional costs to the healthcare system. CONCLUSIONS: Routine HIV screening in high-prevalence jails is cost effective and has a larger impact on public health than targeted testing. Prioritizing sustained funding for routine, jail-based HIV screening programs in high-prevalence areas may be important to realizing the national HIV prevention goals.

      5. Response to a Large HIV Outbreak, Cabell County, West Virginia, 2018-2019external icon
        McClung RP, Atkins AD, Kilkenny M, Bernstein KT, Willenburg KS, Weimer M, Robilotto S, Panneer N, Thomasson E, Adkins E, Lyss SB, Balleydier S, Edwards A, Chen M, Wilson S, Handanagic S, Hogan V, Watson M, Eubank S, Wright C, Thompson A, DiNenno E, Fanfair RN, Ridpath A, Oster AM.
        Am J Prev Med. 2021 Nov;61(5s1):S143-s150.
        INTRODUCTION: In January 2019, the West Virginia Bureau for Public Health detected increased HIV diagnoses among people who inject drugs in Cabell County. Responding to HIV clusters and outbreaks is 1 of the 4 pillars of the Ending the HIV Epidemic in the U.S. initiative and requires activities from the Diagnose, Treat, and Prevent pillars. This article describes the design and implementation of a comprehensive response, featuring interventions from all pillars. METHODS: This study used West Virginia Bureau for Public Health data to identify HIV diagnoses during January 1, 2018-October 9, 2019 among (1) people who inject drugs linked to Cabell County, (2) their sex or injecting partners, or (3) others with an HIV sequence linked to Cabell County people who inject drugs. Surveillance data, including HIV-1 polymerase sequences, were analyzed to estimate the transmission rate and timing of infections using molecular clock phylogenetic analysis. Federal, state, and local partners designed and implemented a comprehensive response during January 2019-October 2019. RESULTS: Of 82 people identified in the outbreak, most were male (60%), were White (91%), and reported unstable housing (80%). In a large molecular cluster containing 56 of 60 (93%) available sequences, 93% of inferred transmissions occurred after January 1, 2018. HIV testing, HIV pre-exposure prophylaxis, and syringe services were rapidly expanded, leading to improved linkage to HIV care and viral suppression. CONCLUSIONS: Evidence of rapid transmission in this outbreak galvanized robust collaboration among federal, state, and local partners, leading to critical improvements in HIV prevention and care services. HIV outbreak response requires increased coordination and creativity to improve service delivery to people affected by rapid HIV transmission.

      6. HIV Cluster and Outbreak Detection and Response: The Science and Experienceexternal icon
        Oster AM, Lyss SB, McClung RP, Watson M, Panneer N, Hernandez AL, Buchacz K, Robilotto SE, Curran KG, Hassan R, Ocfemia MC, Linley L, Perez SM, Phillip SA, France AM.
        Am J Prev Med. 2021 Nov;61(5s1):S130-s142.
        The Respond pillar of the Ending the HIV Epidemic in the U.S. initiative, which consists of activities also known as cluster and outbreak detection and response, offers a framework to guide tailored implementation of proven HIV prevention strategies where transmission is occurring most rapidly. Cluster and outbreak response involves understanding the networks in which rapid transmission is occurring; linking people in the network to essential services; and identifying and addressing gaps in programs and services such as testing, HIV and other medical care, pre-exposure prophylaxis, and syringe services programs. This article reviews the experience gained through 30 HIV cluster and outbreak responses in North America during 2000-2020 to describe approaches for implementing these core response strategies. Numerous jurisdictions that have implemented these response strategies have demonstrated success in improving outcomes related to HIV care and viral suppression, testing, use of prevention services, and reductions in transmission or new diagnoses. Efforts to address important gaps in service delivery revealed by cluster and outbreak detection and response can strengthen prevention efforts broadly through multidisciplinary, multisector collaboration. In this way, the Respond pillar embodies the collaborative, data-guided approach that is critical to the overall success of the Ending the HIV Epidemic in the U.S. initiative.

  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. Disability Among Young Adults With Congenital Heart Defects: Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being 2016-2019external icon
        Downing KF, Oster ME, Klewer SE, Rose CE, Nembhard WN, Andrews JG, Farr SL.
        J Am Heart Assoc. 2021 Oct 20:e022440.
        Background Disabilities have implications for health, well-being, and health care, yet limited information is available on the percentage of adults with congenital heart defects (CHD) living with disabilities. We evaluated the prevalence of disability and associated characteristics among the 2016-2019 CH STRONG (Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being) population-based sample of 19- to 38-year-olds with CHD from 3 US locations. Methods and Results Prevalence of disability types (hearing, vision, cognition, mobility, self-care, living independently) were compared with similarly aged adults from the general population as estimated by the American Community Survey and standardized to the CH STRONG eligible population to reduce nonresponse bias and confounding. Health-related quality of life (HRQOL) was measured via Patient-Reported Outcomes Measurement Information System Global Health Scale T-scores standardized to US 18- to 34-year-olds. Separate multivariable regression models assessed associations between disability and HRQOL. Of 1478 participants, 40% reported disabilities, with cognition most prevalent (29%). Of those reporting disability, 45% ever received disability benefits and 46% were unemployed. Prevalence of disability types were 5 to 8 times higher in adults with CHD than the general population. Those with ≥1 disability had greater odds of being female, and of having non-Hispanic Black maternal race and ethnicity, severe CHD, recent cardiac care, and noncardiac congenital anomalies. On average, adults with CHD and cognition, mobility, and self-care disabilities had impaired mental HRQOL and those with any disability type had impaired physical HRQOL. Conclusions Two of 5 adults with CHD may have disabilities, which are associated with impaired HRQOL. These results may inform healthcare needs and services for this growing population.

    • Communicable Diseases
      1. BACKGROUND: Previous studies have showed that sexually transmitted infections (STI) and human immunodeficiency virus (HIV) testing has varied, but STI prevalence was not estimated among patients during their healthcare visits in which a high-risk sexual partnership was documented. This study estimated gonorrhea, chlamydia, syphilis, and HIV testing rates, and chlamydia and gonorrhea prevalence. METHODS: From the de-identified commercial claims data of OptumLabs® Data Warehouse, we identified men and women aged 15-60 years classified as having high-risk sexual relationships as diagnosis codes: Z72.51 for opposite-sex, Z72.52 for same-sex, and Z72.53 for same-and-opposite-sex relationships, stratified by gender, age group, region, type of health plan, and HIV status. We estimated STI testing rate and prevalence for chlamydia and gonorrhea among patients with high-risk sexual relationships. HIV testing was assessed only in high-risk sexual relationship patients without HIV. RESULTS: Among 8.2 million females and 7.3 million males aged 15-60 years in the database from 2016-2019, 115,884 patients (0.7% of female, 0.8% of male) including 3,535 patients with HIV were diagnosed with high-risk sexual relationships. The testing rates for gonorrhea, chlamydia, syphilis, and HIV were 69.4% (CI:69.1-69.7), 68.9% (CI:68.6-69.2), 43.4% (CI:43.1-43.7), and 41.7% (CI:41.4-42.0), respectively. Among patients with valid chlamydia and gonorrhea tests, 7.2% (CI:7.0-7.5) and 2.6% (CI:2.4-2.8) had positive chlamydia and gonorrhea test results respectively, and varied by type of high-risk sexual relationship. CONCLUSIONS: Our study findings of suboptimal STI screening among patient in high-risk sexual relationships are consistent with previous studies. Administrative records confirmed by lab results indicate a need for STI counselling, testing, and treatment among patients who are diagnosed with high-risk sexual relationships with same-sex, opposite-sex, or same-and-opposite sex partners.

      2. CD4 Count at Entry into Care and at Antiretroviral Therapy Prescription among Adults with Human Immunodeficiency Virus in the United States, 2005-2018external icon
        Lee JS, Humes EA, Hogan BC, Buchacz K, Eron JJ, Gill MJ, Sterling TR, Rebeiro PF, Lima VD, Mayor A, Silverberg MJ, Horberg MA, Moore RD, Althoff KN.
        Clin Infect Dis. 2021 Oct 5;73(7):e2334-e2337.
        From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/μL, and CD4 count at ART prescription increased from 160 to 364 cells/μL.

      3. Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Ugandaexternal icon
        Loevinsohn G, Kigozi G, Kagaayi J, Wawer MJ, Nalugoda F, Chang LW, Quinn TC, Serwadda D, Reynolds SJ, Nelson L, Mills L, Alamo S, Nakigozi G, Kabuye G, Ssekubugu R, Tobian AA, Gray RH, Grabowski MK.
        Clin Infect Dis. 2021 Oct 5;73(7):e1946-e1953.
        BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. RESULTS: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

      4. Optimal Testing Choice and Diagnostic Strategies for Latent Tuberculosis Infection Among US-Born People Living with Human Immunodeficiency Virus (HIV)external icon
        Pettit AC, Stout JE, Belknap R, Benson CA, Séraphin MN, Lauzardo M, Horne DJ, Garfein RS, Maruri F, Ho CS.
        Clin Infect Dis. 2021 Oct 5;73(7):e2278-e2284.
        BACKGROUND: Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with human immunodeficiency virus (HIV; PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. METHODS: We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of US-born PLWH ≥5 years old with valid results for all 3 LTBI tests using standard US cutoffs (≥5 mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. RESULTS: Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15 mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. CONCLUSIONS: LTBI prevalence among this cohort of US-born PLWH was low compared to non-US born persons. TSPOT's higher PPV may make it preferable for testing US-born PLWH at low risk for TB exposure and with high CD4+ counts.

      5. A Prospective Cohort Study in Nonhospitalized Household Contacts With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Symptom Profiles and Symptom Change Over Timeexternal icon
        Yousaf AR, Duca LM, Chu V, Reses HE, Fajans M, Rabold EM, Laws RL, Gharpure R, Matanock A, Wadhwa A, Pomeroy M, Njuguna H, Fox G, Binder AM, Christiansen A, Freeman B, Gregory C, Tran CH, Owusu D, Ye D, Dietrich E, Pevzner E, Conners EE, Pray I, Rispens J, Vuong J, Christensen K, Banks M, O'Hegarty M, Mills L, Lester S, Thornburg NJ, Lewis N, Dawson P, Marcenac P, Salvatore P, Chancey RJ, Fields V, Buono S, Yin S, Gerber S, Kiphibane T, Dasu T, Bhattacharyya S, Westergaard R, Dunn A, Hall AJ, Fry AM, Tate JE, Kirking HL, Nabity S.
        Clin Infect Dis. 2021 Oct 5;73(7):e1841-e1849.
        BACKGROUND: Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection. METHODS: From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time. RESULTS: We identified 47 contacts, median age 24 (3-75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 [68%]) and neurologic (n = 30 [64%]); fever was not commonly reported (n = 9 [19%]). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for <18, 18-49, and ≥50 years of age, respectively; P = .03). CONCLUSIONS: Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.

      6. Patterns of Virus Exposure and Presumed Household Transmission among Persons with Coronavirus Disease, United States, January-April 2020external icon
        Burke RM, Calderwood L, Killerby ME, Ashworth CE, Berns AL, Brennan S, Bressler JM, Morano LH, Lewis NM, Markus TM, Newton SM, Read JS, Rissman T, Taylor J, Tate JE, Midgley CM.
        Emerg Infect Dis. 2021 Sep;27(9):2323-2332.
        We characterized common exposures reported by a convenience sample of 202 US patients with coronavirus disease during January-April 2020 and identified factors associated with presumed household transmission. The most commonly reported settings of known exposure were households and healthcare facilities; among case-patients who had known contact with a confirmed case-patient compared with those who did not, healthcare occupations were more common. Among case-patients without known contact, use of public transportation was more common. Within the household, presumed transmission was highest from older (>65 years) index case-patients and from children to parents, independent of index case-patient age. These findings may inform guidance for limiting transmission and emphasize the value of testing to identify community-acquired infections.

      7. Hepatitis B virus elimination status and strategies in circumpolar countries, 2020external icon
        Haering C, McMahon B, Harris A, Weis N, Lundberg Ederth J, Axelsson M, Olafsson S, Osiowy C, Tomas K, Bollerup S, Liitsola K, Archibald C, Blystad H, Bruce M, Nolen L.
        Int J Circumpolar Health. 2021 Dec;80(1):1986975.
        Hepatitis B virus (HBV) infection remains a global health threat. The World Health Organization (WHO) established a goal to eliminate HBV infection as a public health threat by 2030, and defined targets for key interventions to achieve that goal. We evaluated HBV burden and relevant national recommendations for progress towards WHO targets in circumpolar countries. Viral hepatitis experts of circumpolar countries were surveyed regarding their country's burden of HBV, achievement of WHO targets and national public health authority recommendations for HBV prevention and control. Eight of nine circumpolar countries responded. All countries continue to see new HBV infections. Data about HBV prevalence and progress in reaching WHO 2030 elimination targets are lacking. No country was able to report data for all seven WHO target measures. All countries have recommendations targeting the prevention of mother-to-child transmission. Only the USA and Greenland recommend universal birth dose vaccination. Four countries have recommendations to screen persons at high risk for HBV. Existing recommendations largely address prevention; however, recommendations for universal birth dose vaccination have not been widely introduced. Opportunities remain for the development of trackable targets and national elimination planning to screen and treat for HBV to reduce incidence and mortality.

      8. Developing and Validating an Effective Pediatric and Adolescent HIV Testing Eligibility Screening Tool for High-Volume Entry Points in Ugandaexternal icon
        Katureebe C, Ashburn K, Machekano R, Gill MM, Gross J, Kazooba P, Kiyonga A, Taasi G, Adler M, Nazziwa E, Rivadeneira ED, Kekitiinwa A, Magongo E, Matovu JB, Nantume S, Bitarakwate E.
        J Acquir Immune Defic Syndr. 2021 Nov 1;88(3):290-298.
        INTRODUCTION: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches. METHODS: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. RESULTS: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. CONCLUSIONS: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents.

      9. Adverse event profile and associated factors following surgical voluntary medical male circumcision in two regions of Namibia, 2015-2018external icon
        O'Bryan G, Feldacker C, Ensminger A, Nghatanga M, Brandt L, Shepard M, Billah I, Aupokolo M, Mengistu AT, Forster N, Zemburuka B, Sithole E, Mutandi G, Barnhart S, O'Malley G.
        PLoS One. 2021 ;16(10):e0258611.
        INTRODUCTION: Monitoring clinical safety of voluntary medical male circumcision (VMMC) is critical to minimize risk as VMMC programs for HIV prevention are scaled. This cross-sectional analysis describes the adverse event (AE) profile of a large-scale, routine VMMC program and identifies factors associated with the development, severity, and timing of AEs to provide recommendations for program quality improvement. MATERIALS AND METHODS: From 2015-2018 there were 28,990 circumcisions performed in International Training and Education Center for Health (I-TECH) supported regions of Namibia in collaboration with the Ministry of Health and Social Services. Two routine follow-up visits after VMMC were scheduled to identify clients with AEs. Summary statistics were used to describe characteristics of all VMMC clients and the subset who experienced an AE. We used chi-square tests to evaluate associations between AE timing, patient age, and other patient and AE characteristics. We used a logistic regression model to explore associations between patient characteristics and AE severity. RESULTS: Of the 498 clients with AEs (AE rate of 1.7%), 40 (8%) occurred ≤2 days, 262 (53%) occurred 3-7 days, 161 (32%) between day 8 and 14, and 35 (7%) were ≥15 days post-VMMC. Early AEs (on or before day 2) tended to be severe and categorized as bleeding, while infections were the most common AEs occurring later (p<0.001). Younger clients (aged 10-14 years) experienced more infections, whereas older clients experienced more bleeding (p<0.001). CONCLUSIONS: Almost 40% of AEs occurred after the second follow-up visit, of which 179 (91%) were infections. Improvements in pre-surgical and post-surgical counselling and post-operative educational materials encouraging clients to seek care at any time, adoption of alternative follow-up methods, and the addition of a third follow-up visit may improve outcomes for patients. Enhancing post-surgical counselling and emphasizing wound care for younger VMMC clients and their caregivers could help mitigate elevated risk of infection.

      10. Prevalence of Urogenital Mycoplasma genitalium Infection, United States, 2017 to 2018external icon
        Torrone EA, Kruszon-Moran D, Philips C, Morris MR, Bowden KE, Papp J, Bachmann LH, Weinstock H, Kersh EN.
        Sex Transm Dis. 2021 Nov 1;48(11):e160-e162.
        During the 2017-2018 National Health and Nutrition Examination Survey, urine samples from participants aged 14 to 59 years were tested for Mycoplasma genitalium infection. Overall prevalence was 1.7% (95% confidence interval [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%]).

      11. Impact of the COVID-19 Pandemic on Centers for Disease Control and Prevention-Funded STD Programsexternal icon
        Wright SS, Kreisel KM, Hitt JC, Pagaoa MA, Weinstock HS, Thorpe PG.
        Sex Transm Dis. 2021 Oct 12.
        The COVID-19 pandemic impacted STD services. Of 59 U.S.-funded STD programs, 91% reported a great deal to moderate impact from staff reassignment in April 2020, with 28% of respondents reporting permanent reassignment of DIS staff. Telemedicine was implemented in 44%. Decreases in STD case reports were reported by most jurisdictions.

    • Drug Safety
      1. Trends in Office Visits During Which Opioids Were Prescribed for Adults With Arthritis in the US, 2006-2015external icon
        Santo L, Schappert SM, Hootman JM, Helmick CG.
        Arthritis Care Res (Hoboken). 2021 Oct;73(10):1430-1435.
        OBJECTIVE: To analyze trends for visits to office-based physicians at which opioids were prescribed among adults with arthritis in the US, from 2006 to 2015. METHODS: We analyzed nationally representative data on patient visits to office-based physicians from 2006 to 2015 from the National Ambulatory Medical Care Survey (NAMCS). Visit percentages for first- and any-listed diagnosis of arthritis by age groups and sex were reported. Time points were grouped into 2-year intervals to increase the reliability of estimates. Annual percentage point change and 95% confidence intervals (95% CIs) were reported from linear regression models. RESULTS: From 2006 to 2015, the percentage of visits to office-based physicians by adults with a first-listed diagnosis of arthritis increased from 4.1% (95% CI 3.5%, 4.7%) in 2006-2007 to 5.1% (95% CI 3.9%, 6.6%) in 2014-2015 (P = 0.033). Among these visits, the percentage of visits with opioids prescribed increased from 16.5% (95% CI 13.1%, 20.5%) in 2006-2007 to 25.6% (95% CI 17.9%, 34.6%) in 2014-2015 (P = 0.017). The percentage of visits with any-listed diagnosis of arthritis increased from 6.6% (95% CI 5.9%, 7.4%) in 2006-2007 to 8.4% (95% CI 7.0%, 10.0%) in 2014-2015 (P = 0.001). Among these visits, the percentage of visits with opioids prescribed increased from 17.4% (95% CI 14.6%, 20.4%) in 2006-2007 to 25.0% (95% CI 19.7%, 30.8%) in 2014-2015 (P = 0.004). CONCLUSION: From 2006 to 2015, the percentage of visits to office-based physicians by adults with arthritis increased and the percentage of opioids prescribed at these visits also increased. NAMCS data will allow continued monitoring of these trends after the implementation of the 2016 Centers for Disease Control and Prevention Guideline for prescribing opioids for chronic pain.

    • Environmental Health
      1. Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adultsexternal icon
        Bae S, Kamynina E, Guetterman HM, Farinola AF, Caudill MA, Berry RJ, Cassano PA, Stover PJ.
        Cochrane Database Syst Rev. 2021 Oct 18;10:Cd012649.
        BACKGROUND: Arsenic is a common environmental toxin. Exposure to arsenic (particularly its inorganic form) through contaminated food and drinking water is an important public health burden worldwide, and is associated with increased risk of neurotoxicity, congenital anomalies, cancer, and adverse neurodevelopment in children. Arsenic is excreted following methylation reactions, which are mediated by folate. Provision of folate through folic acid supplements could facilitate arsenic methylation and excretion, thereby reducing arsenic toxicity. OBJECTIVES: To assess the effects of provision of folic acid (through fortified foods or supplements), alone or in combination with other nutrients, in lessening the burden of arsenic-related health outcomes and reducing arsenic toxicity in arsenic-exposed populations. SEARCH METHODS: In September 2020, we searched CENTRAL, MEDLINE, Embase, 10 other international databases, nine regional databases, and two trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing the provision of folic acid (at any dose or duration), alone or in combination with other nutrients or nutrient supplements, with no intervention, placebo, unfortified food, or the same nutrient or supplements without folic acid, in arsenic-exposed populations of all ages and genders. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two RCTs with 822 adults exposed to arsenic-contaminated drinking water in Bangladesh. The RCTs compared 400 µg/d (FA400) or 800 µg/d (FA800) folic acid supplements, given for 12 or 24 weeks, with placebo. One RCT, a multi-armed trial, compared FA400 plus creatine (3 g/d) to creatine alone. We judged both RCTs at low risk of bias in all domains. Due to differences in co-intervention, arsenic exposure, and participants' nutritional status, we could not conduct meta-analyses, and therefore, provide a narrative description of the data. Neither RCT reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies. Folic acid supplements alone versus placebo Blood arsenic. In arsenic-exposed individuals, FA likely reduces blood arsenic concentrations compared to placebo (2 studies, 536 participants; moderate-certainty evidence). For folate-deficient and folate-replete participants who received arsenic-removal water filters as a co-intervention, FA800 reduced blood arsenic levels more than placebo (percentage change (%change) in geometric mean (GM) FA800 -17.8%, 95% confidence intervals (CI) -25.0 to -9.8; placebo GM -9.5%, 95% CI -16.5 to -1.8; 1 study, 406 participants). In one study with 130 participants with low baseline plasma folate, FA400 reduced total blood arsenic (%change FA400 mean (M) -13.62%, standard error (SE) ± 2.87; placebo M -2.49%, SE ± 3.25), and monomethylarsonic acid (MMA) concentrations (%change FA400 M -22.24%, SE ± 2.86; placebo M -1.24%, SE ± 3.59) more than placebo. Inorganic arsenic (InAs) concentrations reduced in both groups (%change FA400 M -18.54%, SE ± 3.60; placebo M -10.61%, SE ± 3.38). There was little to no change in dimethylarsinic acid (DMA) in either group. Urinary arsenic. In arsenic-exposed individuals, FA likely reduces the proportion of total urinary arsenic excreted as InAs (%InAs) and MMA (%MMA) and increases the proportion excreted as DMA (%DMA) to a greater extent than placebo (2 studies, 546 participants; moderate-certainty evidence), suggesting that FA enhances arsenic methylation. In a mixed folate-deficient and folate-replete population (1 study, 352 participants) receiving arsenic-removal water filters as a co-intervention, groups receiving FA had a greater decrease in %InAs (within-person change FA400 M -0.09%, 95% CI -0.17 to -0.01; FA800 M -0.14%, 95% CI -0.21 to -0.06; placebo M 0.05%, 95% CI 0.00 to 0.10), a greater decrease in %MMA (within-person change FA400 M -1.80%, 95% CI -2.53 to -1.07; FA800 M -2.60%, 95% CI -3.35 to -1.85; placebo M 0.15%, 95% CI -0.37 to 0.68), and a greater increase in %DMA (within-person change FA400 M 3.25%, 95% CI 1.81 to 4.68; FA800 M 4.57%, 95% CI 3.20 to 5.95; placebo M -1.17%, 95% CI -2.18 to -0.17), compared to placebo. In 194 participants with low baseline plasma folate, FA reduced %InAs (%change FA400 M -0.31%, SE ± 0.04; placebo M -0.13%, SE ± 0.04) and %MMA (%change FA400 M -2.6%, SE ± 0.37; placebo M -0.71%, SE ± 0.43), and increased %DMA (%change FA400 M 5.9%, SE ± 0.82; placebo M 2.14%, SE ± 0.71), more than placebo. Plasma homocysteine: In arsenic-exposed individuals, FA400 likely reduces homocysteine concentrations to a greater extent than placebo (2 studies, 448 participants; moderate-certainty evidence), in the mixed folate-deficient and folate-replete population receiving arsenic-removal water filters as a co-intervention (%change in GM FA400 -23.4%, 95% CI -27.1 to -19.5; placebo -1.3%, 95% CI -5.3 to 3.1; 1 study, 254 participants), and participants with low baseline plasma folate (within-person change FA400 M -3.06 µmol/L, SE ± 3.51; placebo M -0.05 µmol/L, SE ± 4.31; 1 study, 194 participants). FA supplements plus other nutrient supplements versus nutrient supplements alone In arsenic-exposed individuals who received arsenic-removal water filters as a co-intervention, FA400 plus creatine may reduce blood arsenic concentrations more than creatine alone (%change in GM FA400 + creatine -14%, 95% CI -22.2 to -5.0; creatine -7.0%, 95% CI -14.8 to 1.5; 1 study, 204 participants; low-certainty evidence); may not change urinary arsenic methylation indices (FA400 + creatine: %InAs M 13.2%, SE ± 7.0; %MMA M 10.8, SE ± 4.1; %DMA M 76, SE ± 7.8; creatine: %InAs M 14.8, SE ± 5.5; %MMA M 12.8, SE ± 4.0; %DMA M 72.4, SE ±7.6; 1 study, 190 participants; low-certainty evidence); and may reduce homocysteine concentrations to a greater extent (%change in GM FA400 + creatinine -21%, 95% CI -25.2 to -16.4; creatine -4.3%, 95% CI -9.0 to 0.7; 1 study, 204 participants; low-certainty evidence) than creatine alone. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that FA supplements may benefit blood arsenic concentration, urinary arsenic methylation profiles, and plasma homocysteine concentration versus placebo. There is low-certainty evidence that FA supplements plus other nutrients may benefit blood arsenic and plasma homocysteine concentrations versus nutrients alone. No studies reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies. Given the limited number of RCTs, more studies conducted in diverse settings are needed to assess the effects of FA on arsenic-related health outcomes and arsenic toxicity in arsenic-exposed adults and children.

      2. Maternal urinary OPE metabolite concentrations and blood pressure during pregnancy: The HOME studyexternal icon
        Yang W, Braun JM, Vuong AM, Percy Z, Xu Y, Xie C, Deka R, Calafat AM, Ospina M, Werner E, Yolton K, Cecil KM, Lanphear BP, Chen A.
        Environ Res. 2021 Oct 14:112220.
        BACKGROUND: Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. METHODS: We analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. RESULTS: ICCs of OPEs were 0.17-0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: 0.01, 3.59) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97-9.15). Other OPE metabolites were not significantly associated with HDP. CONCLUSION: Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance.

      3. A Million Persons, A Million Dreams: A Vision For A National Center Of Radiation Epidemiology And Biologyexternal icon
        Boice JD, Quinn B, Al-Nabulsi I, Ansari A, Blake PK, Blattnig SR, Caffrey EA, Cohen SS, Golden AP, Held KD, Jokisch DW, Leggett RW, Mumma MT, Samuels C, Till JE, Tolmachev SY, Yoder RC, Zhou JY, Dauer LT.
        Int J Radiat Biol. 2021 Oct 20:1-50.
        BACKGROUND: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. MATERIALS AND METHODS: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. RESULTS: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. CONCLUSIONS: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

    • Epidemiology and Surveillance
      1. Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) Study: Protocol for a multi-site longitudinal cohortexternal icon
        Edwards LJ, Fowlkes AL, Wesley MG, Kuntz JL, Odean MJ, Caban-Martinez AJ, Dunnigan K, Phillips AL, Grant L, Herring MK, Groom HC, Respet K, Beitel S, Zunie T, Hegmann KT, Kumar A, Joseph G, Poe B, Louzado-Feliciano P, Smith ME, Thiese MS, Schaefer-Solle N, Yoo YM, Silvera CA, Mayo Lamberte J, Mak J, McDonald LC, Stuckey MJ, Kutty P, Arvay ML, Yoon SK, Tyner HL, Burgess JL, Hunt DR, Meece J, Gaglani M, Naleway AL, Thompson MG.
        JMIR Res Protoc. 2021 Oct 7.
        BACKGROUND: Workers critical to emergency response and continuity of essential services during the coronavirus disease 2019 (COVID-19) pandemic are at a disproportionally high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Prospective cohort studies are needed to enhance understanding the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. OBJECTIVE: The Research on the Epidemiology of SARS-CoV-2 in Essential Response personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, examine risk factors for infection and clinical spectrum of illness, and assess effectiveness of vaccination among essential workers. METHODS: The RECOVER multi-site network was initiated in August 2020 and aims to enroll 3,000 healthcare personnel (HCP), first responders, and other essential and frontline workers (EFW) in six U.S. locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for symptoms of COVID-19-like illness (CLI), accessing medical care, and symptom duration are ascertained by text messages, e-mails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and two additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every three months, approximately 28 days after a reverse-transcription-polymerase-chain-reaction (RT-PCR)-confirmed SARS-CoV-2 infection, and 14-28 days after a dose of any COVID-19 vaccine. Beginning in February 2021, household members of RT-PCR-confirmed participants self-collect mid-turbinate nasal swabs daily for ten days. RESULTS: The study observation period began in August 2020 and is currently expected to continue through spring 2022. There are 2,623 actively enrolled RECOVER participants, including 252 participants who were found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at three of six study site locations. CONCLUSIONS: Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT: DERR1-10.2196/31574.

      2. Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelinesexternal icon
        Pollett S, Johansson MA, Reich NG, Brett-Major D, Del Valle SY, Venkatramanan S, Lowe R, Porco T, Berry IM, Deshpande A, Kraemer MU, Blazes DL, Pan-Ngum W, Vespigiani A, Mate SE, Silal SP, Kandula S, Sippy R, Quandelacy TM, Morgan JJ, Ball J, Morton LC, Althouse BM, Pavlin J, van Panhuis W, Riley S, Biggerstaff M, Viboud C, Brady O, Rivers C.
        PLoS Med. 2021 Oct;18(10):e1003793.
        BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

      3. Hospital-level factors associated with death during pneumonia-associated hospitalization among adults-New York City, 2010-2014external icon
        Whittemore K, Garcia KM, Huang CC, Lim S, Daskalakis DC, Vora NM, Lucero DE.
        PLoS One. 2021 ;16(10):e0256678.
        BACKGROUND: In New York City (NYC), pneumonia is a leading cause of death and most pneumonia deaths occur in hospitals. Whether the pneumonia death rate in NYC reflects reporting artifact or is associated with factors during pneumonia-associated hospitalization (PAH) is unknown. We aimed to identify hospital-level factors associated with higher than expected in-hospital pneumonia death rates among adults in NYC. METHODS: Data from January 1, 2010-December 31, 2014 were obtained from the New York Statewide Planning and Research Cooperative System and the American Hospital Association Database. In-hospital pneumonia standardized mortality ratio (SMR) was calculated for each hospital as observed PAH death rate divided by expected PAH death rate. To determine hospital-level factors associated with higher in-hospital pneumonia SMR, we fit a hospital-level multivariable negative binomial regression model. RESULTS: Of 148,172 PAH among adult NYC residents in 39 hospitals during 2010-2014, 20,820 (14.06%) resulted in in-hospital death. In-hospital pneumonia SMRs varied across NYC hospitals (0.77-1.23) after controlling for patient-level factors. An increase in average daily occupancy and membership in the Council of Teaching Hospitals were associated with increased in-hospital pneumonia SMR. CONCLUSIONS: Differences in in-hospital pneumonia SMRs between hospitals might reflect differences in disease severity, quality of care, or coding practices. More research is needed to understand the association between average daily occupancy and in-hospital pneumonia SMR. Additional pneumonia-specific training at teaching hospitals can be considered to address higher in-hospital pneumonia SMR in teaching hospitals.

    • Health Behavior and Risk
      1. Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026)external icon
        Bauermeister JA, Tingler RC, Dominguez C, Dunne EF, Hoesley C, Ho K, Johnson S, Lucas J, Macagna N, Brown E, Gundacker H, Peda M, Jacobson CE, Kramzer L, Singh D, Dezzutti CS, Ayudhya R, Marzinke MA, Piper J, Devlin B, Nuttall J, McGowan I, Hendrix CW, Cranston RD.
        AIDS Behav. 2021 Oct 17.
        This study describes the acceptability of a rectal microbicide gel formulation using dapivirine (DPV) among men and women from two countries (United States and Thailand) participating in the Microbicide Trials Network-026 trial. We evaluated participants' acceptability of a rectal DPV/placebo gel as part of a Phase I trial (N = 26; 18 male, 8 female). Participants reported favorable acceptability of the study gel, with most participants reporting that they liked the gel the same (n = 14; 53.8%) or more (n = 11; 42.4%) than when they started the trial. Over half of participants noted that they would prefer the gel over condoms (n = 13; 50%) or that they liked condoms and the gel equally (n = 8; 30.8%). Side effects across products included leakage (n = 8; 30.8%), diarrhea (n = 4; 15.4%), or soiling (n = 1; 3.8%). The high acceptability of a rectal gel underscores its promise as a short-acting biomedical prevention, warranting future research for HIV prevention.Trial Registration: NCT03239483.

      2. Trends in the Number and Characteristics of HIV Pre-Exposure Prophylaxis Providers in the United States, 2014-2019external icon
        Zhu W, Huang YA, Kourtis AP, Hoover KW.
        J Acquir Immune Defic Syndr. 2021 Nov 1;88(3):282-289.
        BACKGROUND: The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported. METHODS: We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers. RESULTS: The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers. CONCLUSIONS: An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States.

      3. Long-Acting Reversible Contraception, Condom Use, and Sexually Transmitted Infections: A Systematic Review and Meta-analysisexternal icon
        Steiner RJ, Pampati S, Kortsmit KM, Liddon N, Swartzendruber A, Pazol K.
        Am J Prev Med. 2021 Nov;61(5):750-760.
        INTRODUCTION: Given mixed findings regarding the relationship between long-acting reversible contraception and condom use, this systematic review and meta-analysis synthesizes studies comparing sexually transmitted infection‒related outcomes between users of long-acting reversible contraception (intrauterine devices, implants) and users of moderately effective contraceptive methods (oral contraceptives, injectables, patches, rings). METHODS: MEDLINE, Embase, PsycINFO, Global Health, CINAHL, Cochrane Library, and Scopus were searched for articles published between January 1990 and July 2018. Eligible studies included those that (1) were published in the English language, (2) were published in a peer-reviewed journal, (3) reported empirical, quantitative analyses, and (4) compared at least 1 outcome of interest (condom use, sexual behaviors other than condom use, sexually transmitted infection‒related service receipt, or sexually transmitted infections/HIV) between users of long-acting reversible contraception and users of moderately effective methods. In 2020, pooled ORs were calculated for condom use, chlamydia/gonorrhea infection, and trichomoniasis infection; findings for other outcomes were synthesized qualitatively. The protocol is registered on the International Prospective Register of Systematic Reviews (CRD42018109489). RESULTS: A total of 33 studies were included. Long-acting reversible contraception users had decreased odds of using condoms compared with oral contraceptive users (OR=0.43, 95% CI=0.30, 0.63) and injectable, patch, or ring users (OR=0.58, 95% CI=0.48, 0.71); this association remained when limited to adolescents and young adults only. Findings related to multiple sex partners were mixed, and only 2 studies examined sexually transmitted infection testing, reporting mainly null findings. Pooled estimates for chlamydia and/or gonorrhea were null, but long-acting reversible contraception users had increased odds of trichomoniasis infection compared with oral contraceptive users (OR=2.01, 95% CI=1.11, 3.62). DISCUSSION: Promoting condom use specifically for sexually transmitted infection prevention may be particularly important among long-acting reversible contraception users at risk for sexually transmitted infections, including adolescents and young adults.

    • Health Disparities
      1. Race-Based Medical Mistrust, HIV-Related Stigma, and ART Adherence in a Diverse Sample of Men Who Have Sex with Men with HIVexternal icon
        Meyers-Pantele SA, Sullivan P, Mansergh G, Hirshfield S, Stephenson R, Horvath KJ.
        AIDS Behav. 2021 Oct 20.
        Disparities in antiretroviral treatment (ART) access by race for men who have sex with men (MSM) with HIV persist. We assessed whether race-based medical mistrust and HIV stigma impact ART adherence among MSM with HIV. Longitudinal data were drawn from a RCT of a messaging intervention to promote sexual health among MSM. Regression models tested associations between baseline race-based medical mistrust, HIV stigma, and ART adherence at follow-up. In multivariable models with the overall sample of MSM with HIV (n = 383), baseline medical mistrust was negatively associated with ART adherence 3-months post-baseline. Among participants of color (i.e., Black/African American, Hispanic/Latino, or another race; n = 301), HIV stigma was negatively associated with optimal ART adherence 6-months post-baseline. Medical mistrust was longitudinally associated with reduced ART adherence among racially and ethnically diverse MSM with HIV. HIV-related services might prioritize patients reporting medical mistrust for additional supports.

      2. Healthcare Access and Utilization for Young Adults With Disability: U.S., 2014-2018external icon
        Verlenden JV, Zablotsky B, Yeargin-Allsopp M, Peacock G.
        J Adolesc Health. 2021 Oct 15.
        PURPOSE: Young adults with disability experience barriers to healthcare access and are at risk for not receiving needed services as they transition from pediatric to adult health systems. This study examined patterns of healthcare utilization for young adults with disability and potential barriers to receipt of care. METHODS: Data from the 2014 to 2018 National Health Interview Survey were analyzed to examine differences in service utilization, unmet need, care satisfaction, and financial worry between young adults (18-30 years) with and without disability (unweighted n = 15,710). Odds ratios were adjusted for individual, family, and interview characteristics. RESULTS: Compared to those without disability, young adults with disability were more likely to have had an emergency room visit in the past year (39.2% vs. 19.5%). They were also more likely to have a usual source of care when sick (82.2% vs. 75%). Among young adults who affirmed they had a usual place of care, those with disability were more likely to use the emergency room as their usual place of care (5.3% vs. 1.8%). A greater percentage of young adults with disability delayed medical care due to cost (19.1% vs. 8.9%) and reported an unmet medical need (21% vs. 10.2%). CONCLUSIONS: Findings highlight gaps in healthcare access for young adults with disability. Differences in healthcare utilization patterns for young adults with disability and factors that may negatively influence health outcomes for this population were found. Further research focused on the continuity of healthcare services in this age group through the healthcare transition period may provide additional insight into these discrepancies.

      3. CONTEXT: During the COVID-19 pandemic, demand for telehealth services increased to reduce disease exposure for patients and providers and to meet preexisting demand for physician services in health resource shortage areas. OBJECTIVE: To estimate self-reported telehealth availability, equipment for accessing telehealth, and telehealth usage among Medicare beneficiaries during the COVID-19 pandemic. DESIGN: We used data from the 2020 Medicare Current Beneficiary Survey (MCBS) COVID-19 Fall Supplement Public Use File to estimate the weighted percentages of beneficiaries who had (a) access to telehealth before or during COVID-19; (b) equipment for accessing telehealth; and (c) telehealth visits during COVID-19. We used logistic regression to examine sociodemographic factors associated with telehealth usage. PARTICIPANTS: Beneficiaries who participated in the MCBS COVID-19 Fall Supplements. RESULTS: During October and November 2020, telehealth appointments offered by providers were available to 63.8% (95% confidence interval [CI], 61.8-65.9) of Medicare beneficiaries who had accessed medical care by telephone or video. Among those, only 18.0% (95% CI, 16.1-19.9) had been offered telehealth before the pandemic. The majority of beneficiaries (92.2%; 95% CI, 91.2-93.1) had 1 or more types of equipment available for accessing telehealth, but only 44.9% (95% CI, 43.0-46.9) had had a telehealth visit since July 1, 2020. Older adults, minorities, those with a lower income, and non-English speakers had less availability of telehealth equipment. Patient characteristics were significantly (P < .05) associated with telehealth use, including age, sex, race/ethnicity, and equipment availability. CONCLUSION: Telehealth availability for Medicare beneficiaries increased substantially during the COVID-19 pandemic. Even with the improvement in telehealth offerings and use hastened by the pandemic, gaps in access and use still exist. Effectiveness and implementation research can find ways to close gaps in telehealth services between vulnerable and underrepresented populations and counterparts.

      4. How cancer programs identify and address the financial burdens of rural cancer patientsexternal icon
        Petermann V, Zahnd WE, Vanderpool RC, Eberth JM, Rohweder C, Teal R, Vu M, Stradtman L, Frost E, Trapl E, Koopman Gonzalez S, Vu T, Ko LK, Cole A, Farris PE, Shannon J, Lee J, Askelson N, Seegmiller L, White A, Edward J, Davis M, Wheeler SB.
        Support Care Cancer. 2021 Oct 16.
        PURPOSE: Financial toxicity is associated with negative patient outcomes, and rural populations are disproportionately affected by the high costs of cancer care compared to urban populations. Our objective was to (1) understand cancer programs' perceptions of rural-urban differences in cancer patients' experiences of financial hardship, (2) evaluate the resources available to cancer patients across the rural-urban continuum, and (3) determine how rural and urban health care teams assess and address financial distress in cancer patients. METHODS: Seven research teams within the Cancer Prevention and Research Control Network conducted semi-structured interviews with cancer program staff who have a role in connecting cancer patients with financial assistance services in both rural and urban counties. Interviews were audio-recorded and transcribed. We identified themes using descriptive content and thematic analysis. RESULTS: We interviewed 35 staffs across 29 cancer care programs in seven states, with roughly half of respondents from programs in rural counties. Participants identified differences in rural and urban patients' experiences of financial hardship related to distance required to travel for treatment, underinsurance, and low socioeconomic status. Insufficient staffing was an identified barrier to addressing rural and urban patients' financial concerns. CONCLUSIONS: Improved financial navigation services could mitigate the effects of financial toxicity experienced by cancer patients, particularly rural patients, throughout treatment and survivorship. Future research is needed to improve how cancer programs assess financial hardship in patients and to expand financial navigation services to better serve rural cancer patients.

    • Health Economics
      1. An economic evaluation of an intervention to increase demand for medical male circumcision among men aged 25-49 years in South Africaexternal icon
        Holmes M, Mukora R, Mudzengi D, Charalambous S, Chetty-Makkan CM, Kisbey-Green H, Maraisane M, Grund J.
        BMC Health Serv Res. 2021 Oct 15;21(1):1097.
        BACKGROUND: Studies estimate that circumcising men between the ages of 20-30 years who have exhibited previous risky sexual behaviour could reduce overall HIV prevalence. Demand creation strategies for medical male circumcision (MMC) targeting men in this age group may significantly impact these prevalence rates. OBJECTIVES: The objective of this study is to evaluate the cost-effectiveness and cost-benefit of an implementation science, pre-post study designed to increase the uptake of male circumcision for ages 25-49 at a fixed MMC clinic located in Gauteng Province, South Africa. METHODS: A health care provider perspective was utilised to collect all costs. Costs were compared between the standard care scenario of routine outreach strategies and a full intervention strategy. Cost-effectiveness was measured as cost per mature man enrolled and cost per mature man circumcised. A cost-benefit analysis was employed by using the Bernoulli model to estimate the cases of HIV averted due to medical male circumcision (MMC), and subsequently translated to averted medical costs. RESULTS: In the 2015 intervention, the cost of the intervention was $9445 for 722 men. The total HIV treatment costs averted due to the intervention were $542,491 from a public care model and $378,073 from a private care model. The benefit-cost ratio was 57.44 for the public care model and 40.03 for the private care model. The net savings of the intervention were $533,046 or $368,628 - depending on treatment in a public or private setting. CONCLUSIONS: The intervention was cost-effective compared to similar MMC demand interventions and led to statistically significant cost savings per individual enrolled.

      2. Estimated economic burden of cancer associated with suboptimal diet in the United Statesexternal icon
        Khushalani JS, Cudhea FP, Ekwueme DU, Ruan M, Shan Z, Harris DM, Mozaffarian D, Zhang FF.
        Cancer Causes Control. 2021 Oct 15.
        PURPOSE: Suboptimal diet is a preventable cause of cancer. We aimed to estimate the economic burden of diet-associated cancer among US adults. METHODS: We used a Comparative Risk Assessment model to quantify the number of new cancer cases attributable to seven dietary factors among US adults ages 20 + years. A Markov cohort model estimated the 5-year medical costs for 15 diet-associated cancers diagnosed in 2015. We obtained dietary intake from 2013 to 2016 National Health and Nutrition Examination Survey, cancer incidence, and survival from 2008 to 2014 Surveillance, Epidemiology, and End Results (SEER) program, and medical costs from 2007 to 2013 linked SEER-Medicare data. RESULTS: The estimated 5-year medical costs of new diet-associated cancer cases diagnosed in 2015 were $7.44 (2018 US$). Colorectal cancer had the largest diet-related 5-year medical costs of $5.32B. Suboptimal consumption of whole grains ($2.76B), dairy ($1.82B), and high consumption of processed meats ($1.5B) accounted for the highest medical costs. Per-person medical costs attributable to suboptimal diet vary by gender, race, and age group. CONCLUSIONS: Suboptimal diet contributes substantially to the economic burden of diet-associated cancers among US adults. This study highlights the need to implement population-based strategies to improve diet and reduce cancer burden in the US.

      3. The health and economic benefits of tests that predict future progression to tuberculosis diseaseexternal icon
        Menzies NA, Shrestha S, Parriott A, Marks SM, Hill AN, Dowdy DW, Shete PB, Cohen T, Salomon JA.
        Epidemiology. 2021 Sep 9.
        BACKGROUND: Effective targeting of latent tuberculosis infection (LTBI) treatment requires identifying those most likely to progress to tuberculosis (TB). We estimated the potential health and economic benefits of diagnostics with improved discrimination for LTBI that will progress to TB. METHODS: A base-case scenario represented current LTBI testing and treatment services in the United States in 2020, with diagnosis via interferon-gamma release assay (IGRA). Alternative scenarios represented tests with higher positive predictive value (PPV) for future TB but similar price to IGRA, and scenarios that additionally assumed higher treatment initiation and completion. We predicted outcomes using multiple transmission-dynamic models calibrated to different geographic areas, and estimated costs from a societal perspective. RESULTS: In 2020, 2.1% (range across model results: 1.1%-3.4%) of individuals with LTBI were predicted to develop TB in their remaining lifetime. For IGRA, we estimated the PPV for future TB as 1.3% (0.6%-1.8%). Relative to IGRA, we estimated a test with 10% PPV would reduce treatment volume by 87% (82%-94%), reduce incremental costs by 30% (15%-52%), and increase quality-adjusted life years by 3% (2%-6%). Cost reductions and health improvements were substantially larger for scenarios in which higher PPV for future TB was associated with greater initiation and completion of treatment. CONCLUSIONS: We estimated that tests with better predictive performance would substantially reduce the number of individuals treated to prevent TB, but would have a modest impact on incremental costs and health impact of TB prevention services, unless accompanied by greater treatment acceptance and completion.

      4. Modeling the Cost-Effectiveness of Express Multisite Gonorrhea Screening Among Men Who Have Sex With Men in the United Statesexternal icon
        Earnest R, Rönn MM, Bellerose M, Menon-Johansson AS, Berruti AA, Chesson HW, Gift TL, Hsu KK, Testa C, Zhu L, Malyuta Y, Menzies NA, Salomon JA.
        Sex Transm Dis. 2021 Nov 1;48(11):805-812.
        BACKGROUND: Men who have sex with men (MSM) experience high rates of gonococcal infection at extragenital (rectal and pharyngeal) anatomic sites, which often are missed without asymptomatic screening and may be important for onward transmission. Implementing an express pathway for asymptomatic MSM seeking routine screening at their clinic may be a cost-effective way to improve extragenital screening by allowing patients to be screened at more anatomic sites through a streamlined, less costly process. METHODS: We modified an agent-based model of anatomic site-specific gonococcal infection in US MSM to assess the cost-effectiveness of an express screening pathway in which all asymptomatic MSM presenting at their clinic were screened at the urogenital, rectal, and pharyngeal sites but forewent a provider consultation and physical examination and self-collected their own samples. We calculated the cumulative health effects expressed as gonococcal infections and cases averted over 5 years, labor and material costs, and incremental cost-effectiveness ratios for express versus traditional scenarios. RESULTS: The express scenario averted more infections and cases in each intervention year. The increased diagnostic costs of triple-site screening were largely offset by the lowered visit costs of the express pathway and, from the end of year 3 onward, this pathway generated small cost savings. However, in a sensitivity analysis of assumed overhead costs, cost savings under the express scenario disappeared in the majority of simulations once overhead costs exceeded 7% of total annual costs. CONCLUSIONS: Express screening may be a cost-effective option for improving multisite anatomic screening among US MSM.

      5. BACKGROUND: Outreach screening is a common strategy for detecting cases of syphilis in high-risk populations. New rapid syphilis tests allow for quicker response times and may alter the costs of detecting and treating syphilis in nonclinical settings. METHODS: Between May and October of 2017, we collected detailed retrospective cost data from 2 outreach screening programs engaging people experiencing homelessness and LGBTQ populations. Comprehensive and retrospective cost information, disaggregated by cost category, programmatic activity, and source of support, was collected during and after the testing period. RESULTS: Across all sites, rapid syphilis tests were conducted on 595 people at an average cost of $213 per person. Twenty-three cases of syphilis were confirmed and treated for an average cost of $5517 per case, ranging from $3604 at a rehabilitation facility to $13,140 at LGBTQ venues served by a mobile clinic. Personnel contributed the most to total costs (56.4%), followed by supplies (12.8%) and the use of buildings (10.4%). Expenditures by programmatic activity varied substantially across sites. CONCLUSIONS: Testing costs varied between venues, reflecting differences in the models used and intensity of services provided. Although staff costs are the major driver, buildings and supplies costs are also significant. Our findings suggest that outreach screenings using rapid syphilis tests may be a feasible and cost-effective tool for health departments when targeting known high-prevalence areas and hard-to-reach populations.

    • Healthcare Associated Infections
      1. Bioaerosol Sampling for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Referral Center with Critically Ill Coronavirus Disease 2019 (COVID-19) Patients March-May 2020external icon
        Lane MA, Brownsword EA, Babiker A, Ingersoll JM, Waggoner J, Ayers M, Klopman M, Uyeki TM, Lindsley WG, Kraft CS.
        Clin Infect Dis. 2021 Oct 5;73(7):e1790-e1794.
        BACKGROUND: Previous research has shown that rooms of patients with coronavirus disease 2019 (COVID-19) present the potential for healthcare-associated transmission through aerosols containing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, data on the presence of these aerosols outside of patient rooms are limited. We investigated whether virus-containing aerosols were present in nursing stations and patient room hallways in a referral center with critically ill COVID-19 patients. METHODS: Eight National Institute for Occupational Safety and Health BC 251 2-stage cyclone samplers were set up throughout 6 units, including nursing stations and visitor corridors in intensive care units and general medical units, for 6 h each sampling period. Samplers were placed on tripods which held 2 samplers positioned 102 cm and 152 cm above the floor. Units were sampled for 3 days. Extracted samples underwent reverse transcription polymerase chain reaction for selected gene regions of the SARS-CoV-2 virus nucleocapsid and the housekeeping gene human RNase P as an internal control. RESULTS: The units sampled varied in the number of laboratory-confirmed COVID-19 patients present on the days of sampling. Some of the units included patient rooms under negative pressure, while most were maintained at a neutral pressure. Of 528 aerosol samples collected, none were positive for SARS-CoV-2 RNA by the estimated limit of detection of 8 viral copies/m3 of air. CONCLUSIONS: Aerosolized SARS-CoV-2 outside of patient rooms was undetectable. While healthcare personnel should avoid unmasked close contact with each other, these findings may provide reassurance for the use of alternatives to tight-fitting respirators in areas outside of patient rooms during the current pandemic.

    • Immunity and Immunization
      1. An Evaluation of Dose-related HPV Vaccine Effectiveness Using Central Registries in Michiganexternal icon
        Gargano JW, You M, Potter R, Alverson G, Swanson R, Saraiya M, Markowitz LE, Copeland G.
        Cancer Epidemiol Biomarkers Prev. 2021 Oct 18.
        BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). METHODS: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI 60-71%) for UTD, 33% (95% CI 18-46%) for 2 doses-not UTD, and 40% (95% CI 27-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI 64-79%) for UTD, 39% (95% CI 10-58%) for 2 doses-not UTD, and 48% (95% CI 25-63%) for 1 dose. VE was higher for vaccination at age <20 than {greater than or equal to}20 years. CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

      2. Adenoviral vector-based platforms for developing effective vaccines to combat respiratory viral infectionsexternal icon
        Elkashif A, Alhashimi M, Sayedahmed EE, Sambhara S, Mittal SK.
        Clin Transl Immunology. 2021 ;10(10):e1345.
        Since the development of the first vaccine against smallpox over two centuries ago, vaccination strategies have been at the forefront of significantly impacting the incidences of infectious diseases globally. However, the increase in the human population, deforestation and climate change, and the rise in worldwide travel have favored the emergence of new viruses with the potential to cause pandemics. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a cruel reminder of the impact of novel pathogens and the suboptimal capabilities of conventional vaccines. Therefore, there is an urgent need to develop new vaccine strategies that allow the production of billions of doses in a short duration and are broadly protective against emerging and re-emerging infectious diseases. Extensive knowledge of the molecular biology and immunology of adenoviruses (Ad) has favored Ad vectors as platforms for vaccine design. The Ad-based vaccine platform represents an attractive strategy as it induces robust humoral and cell-mediated immune responses and can meet the global demand in a pandemic situation. This review describes the status of Ad vector-based vaccines in preclinical and clinical studies for current and emerging respiratory viruses, particularly coronaviruses, influenza viruses and respiratory syncytial viruses.

    • Informatics
      1. Uncertainty in Geospatial Health: Challenges and Opportunities Aheadexternal icon
        Delmelle E, Desjardins MR, Jung P, Owusu C, Lan Y, Hohl A, Dony C.
        Ann Epidemiol. 2021 Oct 14.
        PURPOSE: Uncertainty is not always well captured, understood, or modeled properly, and can bias the robustness of complex relationships, such as the association between the environment and public health through exposure, estimates of geographic accessibility and cluster detection, to name a few. METHODS: We review current challenges and future opportunities as geospatial data and analyses are applied to the field of public health. We are particularly interested in the sources of uncertainty in geospatial data and how this uncertainty may propagate in spatial analysis. RESULTS: We present opportunities to reduce the magnitude and impact of uncertainty. Specifically, we focus on (1) the use of multiple reference data sources to reduce geocoding errors, (2) the validity of online geocoders and how confidentiality (e.g. HIPAA) may be breached, (3) use of multiple reference data sources to reduce geocoding errors, (4) the impact of geoimputation techniques on travel estimates, (5) residential mobility and how it affects accessibility metrics and clustering, and (6) modeling errors in the American Community Survey. Our paper discusses how to communicate spatial and spatiotemporal uncertainty, and high performance computing to conduct large amounts of simulations to ultimately increase statistical robustness for studies in public health. CONCLUSIONS: Our paper contributes to recent efforts to fill in knowledge gaps at the intersection of spatial uncertainty and public health.

    • Laboratory Sciences
      1. Successful Implementation of a Rapid Screening Tool for Hantavirus Cardiopulmonary Syndromeexternal icon
        Oliver TT, Dyal JW, Talker DL, Safaeian S, Yazzie D, Kofman AD, D'Andrea SM, Saleki M, Ingall GB, Choi MJ, Antone-Nez R.
        Am J Clin Pathol. 2021 Oct 19.
        OBJECTIVES: Hantavirus is endemic in the Four Corners region of Arizona, Colorado, New Mexico, and Utah, and hantavirus cardiopulmonary syndrome (HCPS) disproportionately affects the Navajo Nation. We describe the application of a rapid screening tool for identification of HCPS. METHODS: A rapid screening tool for HCPS was implemented at Tséhootsooí Medical Center (TMC) in collaboration with academic partners. RESULTS: Since its implementation in 2016, 20 TMC staff members have been trained to perform this test, and 189 screens for HCPS have been reported. Although hantavirus infection is rare even in high-risk areas, use of this tool resulted in the identification of 4 acute cases of hantavirus infection. CONCLUSIONS: The results demonstrate the successful implementation of a 5-point screening tool for hantavirus infection in an endemic setting by a laboratory in a small community hospital.

      2. Acquisition of Ciprofloxacin Resistance Among an Expanding Clade of β-Lactamase-Positive, Serogroup Y Neisseria meningitidis in the United Statesexternal icon
        Potts CC, Retchless AC, McNamara LA, Marasini D, Reese N, Swint S, Hu F, Sharma S, Blain AE, Lonsway D, Karlsson M, Hariri S, Fox LM, Wang X.
        Clin Infect Dis. 2021 Oct 5;73(7):1185-1193.
        BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA) have been recently reported in the United States. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011 to February 2020 to identify IMD cases caused by strains with blaROB-1- or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1- containing US isolates with wild-type gyrA were identified from 2013 to 2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from 6 other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to 6 CCs and contained 10 unique gyrA alleles; 7 were similar or identical to alleles from Neisseria lactamica or Neisseria gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the United States. The emerging dual resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.

      3. We developed a quantitative method for analyzing nicotine and menthol in e-cigarette, or vaping, products (EVPs). These products may adversely impact health through inhalational exposure to addictive and harmful chemicals. The presence of unknown substances in do-it-yourself e-liquids, counterfeits, or unregulated products may increase exposure to harmful chemicals, as underscored by the 2019 EVP use-associated lung injury (EVALI) outbreak. To minimize these risks, it is important to accurately quantify nicotine and menthol in e-liquids and aerosol emissions to evaluate EVP authenticity, verify product label accuracy, and identify potentially hazardous products. We developed a simple, versatile, high-throughput method using isotope-dilution gas chromatography-mass spectrometry for quantifying nicotine and menthol concentrations in both e-liquid contents and machine-generated aerosol emissions of EVPs. Rigorous validation has demonstrated that the method is specific, precise (CV<2.71%), accurate (percent error ≤7.0%), and robust. Linear calibration ranges from 0.01 to 1.00 mg/ml for both analytes was achieved, corresponding to expected analyte levels in e-liquids and machine-generated EVP aerosols. Limits of detection (LODs) in the final 10-ml sample extract were 0.4 μg/ml for nicotine and 0.2 μg/ml for menthol. The method was used to analyze aerosol emissions of 141 EVPs associated with the 2019 EVALI outbreak; detectable levels of nicotine (2.19-59.5 mg/g of aerosol) and menthol (1.09-10.69 mg/g of aerosol) were observed in 28 and 11%, respectively, of the samples analyzed. Nicotine was not detected in any of the tetrahydrocannabinol (THC), cannabidiol (CBD), or oil-based products, while menthol (2.95 mg/g of aerosol) was only detected in one of these products (THC-labeled). The analytical method can be used to quantify nicotine and menthol concentrations in the e-liquids and aerosols from a range of EVPs, and these findings highlight a difference between e-cigarette and other vaping products.

      4. Evaluation of methods for detection of β-lactamase production in MSSAexternal icon
        Skov R, Lonsway DR, Larsen J, Larsen AR, Samulioniené J, Limbago BM.
        J Antimicrob Chemother. 2021 May 12;76(6):1487-1494.
        OBJECTIVES: Correct determination of penicillin susceptibility is pivotal for using penicillin in the treatment of Staphylococcus aureus infections. This study examines the performance of MIC determination, disc diffusion and a range of confirmatory tests for detection of penicillin susceptibility in S. aureus. METHODS: A total of 286 consecutive penicillin-susceptible S. aureus blood culture isolates as well as a challenge set of 62 MSSA isolates were investigated for the presence of the blaZ gene by PCR and subjected to penicillin-susceptibility testing using broth microdilution MIC determination, disc diffusion including reading of the zone edge, two nitrocefin tests and the cloverleaf test. RESULTS: Using PCR-based detection of blaZ as the gold standard, both broth microdilution MIC testing and disc diffusion testing resulted in a relatively low accuracy (82%-93%) with a sensitivity ranging from 49%-93%. Among the confirmatory tests, the cloverleaf test performed with 100% accuracy, while zone edge interpretation and nitrocefin-based tests increased the sensitivity of β-lactamase detection to 96%-98% and 82%-96% when using MIC determination or disc diffusion as primary test, respectively. CONCLUSIONS: This investigation showed that reliable and accurate detection of β-lactamase production in S. aureus can be obtained by MIC determination or penicillin disc diffusion followed by interpretation of the zone edge as a confirmatory test for apparently penicillin-susceptible isolates. The more cumbersome cloverleaf test can also be used. Nitrocefin-based tests should not be used as the only test for confirmation of a presumptive β-lactamase-negative isolate.

      5. Development of a new peptide-bead coupling method for an all peptide-based Luminex multiplexing assay for detection of Plasmodium falciparum antibody responsesexternal icon
        Wakeman BS, Shakamuri P, McDonald MA, Weinberg J, Svoboda P, Murphy MK, Kariuki S, Mace K, Elder E, Rivera H, Qvarnstrom Y, Pohl J, Shi YP.
        J Immunol Methods. 2021 Sep 21;499:113148.
        Using a recombinant protein antigen for antibody testing shows a sum of antibody responses to multiple different immune epitopes existing in the protein antigen. In contrast, the antibody testing to an immunogenic peptide epitope reflects a singular antibody response to the individual peptide epitope. Therefore, using a panel of peptide epitopes provides an advantage for profiling multiple singular antibody responses with potential to estimate recent malaria exposure in human infections. However, transitioning from malaria immune epitope peptide-based ELISA to an all peptide bead-based multiplex Luminex assay presents some challenges including variation in the ability of different peptides to bind beads. The aim of this study was to develop a peptide coupling method while demonstrating the utility of these peptide epitopes from multiple stage antigens of Plasmodium falciparum for measuring antibodies. Successful coupling of peptide epitopes to beads followed three steps: 1) development of a peptide tag appended to the C-terminus of each peptide epitope consisting of beta-alanine-lysine (x 4)--cysteine, 2) bead modification with a high concentration of adipic acid dihydrazide, and 3) use of the peptide epitope as a blocker in place of the traditional choice, bovine serum albumin (BSA). This new method was used to couple 12 peptide epitopes from multiple stage specific antigens of P. falciparum, 1 Anopheles mosquito salivary gland peptide, and 1 Epstein-Barr virus peptide as an assay control. The new method was applied to testing of IgG in pooled samples from 30 individuals with previously repeated malaria exposure in western Kenya and IgM and IgG in samples from 37 U.S. travelers with recent exposure to malaria. The new peptide-bead coupling method and subsequent multiplex Luminex assay showed reliable detection of IgG to all 14 peptides in Kenyan samples. Among 37 samples from U.S. travelers recently diagnosed with malaria, IgM and IgG to the peptide epitopes were detected with high sensitivity and variation. Overall, the U.S. travelers had a much lower positivity rates of IgM than IgG to different peptide epitopes, ranging from a high of 62.2% positive for one epitope to a low of only 5.4% positive for another epitope. In contrast, the travelers had IgG positive rates from 97.3% to 91.9% to various peptide epitopes. Based on the different distribution in IgM and IgG positivity to overall number of peptide epitopes and to the number of pre-erythrocytic, erythrocytic, gametocytic, and salivary stage epitopes at the individual level, four distinct patterns of IgM and IgG responses among the 37 samples from US travelers were observed. Independent peptide-bead coupling and antibody level readout between two different instruments also showed comparable results. Overall, this new coupling method resolves the peptide-bead coupling challenge, is reproducible, and can be applied to any other immunogenic peptide epitopes. The resulting all peptide bead-based multiplex Luminex assay can be expanded to include other peptide epitopes of P. falciparum, different malaria species, or other diseases for surveillance, either in US travelers or endemic areas.

      6. Purification of native histidine-rich protein 2 (nHRP2) from Plasmodium falciparum culture supernatant, infected RBCs, and parasite lysateexternal icon
        Singh B, McCaffery JN, Kong A, Ah Y, Wilson S, Chatterjee S, Tomar D, Aidoo M, Udhayakumar V, Rogier E.
        Malar J. 2021 Oct 17;20(1):405.
        BACKGROUND: Despite the widespread use of histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs), purified native HRP2 antigen is not standardly used in research applications or assessment of RDTs used in the field. METHODS: This report describes the purification of native HRP2 (nHRP2) from the HB3 Plasmodium falciparum culture strain. As this culture strain lacks pfhrp3 from its genome, it is an excellent source of HRP2 protein only and does not produce the closely-related HRP3. The nHRP2 protein was isolated from culture supernatant, infected red blood cells (iRBCs), and whole parasite lysate using nickel-metal chelate chromatography. Biochemical characterization of nHRP2 from HB3 culture was conducted by SDS-PAGE and western blotting, and nHRP2 was assayed by RDT, ELISA, and bead-based immunoassay. RESULTS: Purified nHRP2 was identified by SDS-PAGE and western blot as a - 60 kDa protein that bound anti-HRP-2 monoclonal antibodies. Mouse anti-HRP2 monoclonal antibody was found to produce high optical density readings between dilutions of 1:100 and 1:3,200 by ELISA with assay signal observed up to a 1:200,000 dilution. nHRP2 yield from HB3 culture by bead-based immunoassay revealed that both culture supernatant and iRBC lysate were practical sources of large quantities of this antigen, producing a total yield of 292.4 µg of nHRP2 from two pooled culture preparations. Assessment of nHRP2 recognition by RDTs revealed that Carestart Pf HRP2 and HRP2/pLDH RDTs detected purified nHRP2 when applied at concentrations between 20.6 and 2060 ng/mL, performing within a log-fold dilution of commercially-available recombinant HRP2. The band intensity observed for the nHRP2 dilutions was equivalent to that observed for P. falciparum culture strain dilutions of 3D7 and US06 F Nigeria XII between 12.5 and 1000 parasites/µL. CONCLUSIONS: Purified nHRP2 could be a valuable reagent for laboratory applications as well as assessment of new and existing RDTs prior to their use in clinical settings. These results establish that it is possible to extract microgram quantities of the native HRP2 antigen from HB3 culture and that this purified protein is well recognized by existing monoclonal antibody lines and RDTs.

      7. The genome of Borrelia spp. consists of an approximate 1 megabase chromosome and multiple linear and circular plasmids. We previously described a multiplex PCR assay to detect plasmids in the North American Borrelia miyamotoi strains LB-2001 and CT13-2396. The primer pair sets specific for each plasmid were derived from the genome sequence for B. miyamotoi strain CT13-2396, because the LB-2001 complete sequence had not been generated. The recent completion of the LB-2001 genome sequence revealed a distinct number of plasmids (n = 12) that differed from CT13-2396 (n = 14). Notable was a 97-kilobase plasmid in LB-2001, not present in CT13-2396, that appeared to be a rearrangement of the circular plasmids of strain CT13-2396. Strain LB-2001 contained two plasmids, cp30-2 and cp24, that were not annotated for strain CT13-2396. Therefore, we re-evaluated the original CT13-2396-derived multiplex PCR primer pairs and determined their location in the LB-2001 plasmids. We modified the original multiplex plasmid PCR assay for strain LB-2001 to include cp30-2 and cp24. We also determined which LB-2001 plasmids corresponded to the amplicons generated from the original CT13-2396 primer sets. These observations provide a more precise plasmid profile based on the multiplex PCR assay and reflect the complexity of gene rearrangements that occur in B. miyamotoi strains isolated from the same geographic region.

    • Maternal and Child Health
      1. SARS-CoV-2 Infection among Pregnant and Postpartum Women, Kenya, 2020-2021external icon
        Otieno NA, Azziz-Baumgartner E, Nyawanda BO, Oreri E, Ellington S, Onyango C, Emukule GO.
        Emerg Infect Dis. 2021 Sep;27(9):2497-2499.
        We determined incidence of severe acute respiratory syndrome coronavirus 2 and influenza virus infections among pregnant and postpartum women and their infants in Kenya during 2020-2021. Incidence of severe acute respiratory syndrome coronavirus 2 was highest among pregnant women, followed by postpartum women and infants. No influenza virus infections were identified.

    • Occupational Safety and Health
      1. In the growing literature on employment quality and health, poor quality of employment is generally associated with poor health. However, this association may not be uniform for men and women if unpaid caregiving labor is taken into consideration. How paid and unpaid labor is performed varies across societies because of differences in both state support for families and labor market penalties for women. Applying a gender lens to a welfare regime typology, we investigated the relationship between poor-quality employment and poor health for men and women. For each of five welfare regime types, we hypothesized if men or women would be more strongly affected by poor-quality employment based on the regime's family support policies and labor practices. Our analysis of 18 countries using the 2015 European and American Working Conditions Surveys data largely supported our hypotheses. In countries that support traditional gender roles with high state expenditure and have labor markets that penalize women, the association between poor-quality employment and health was stronger for men. The association was stronger for women in countries that rely on women to provide unpaid caregiving without substantial state support. In countries with apparently gender-neutral expectations for both paid work and unpaid caregiving work, no difference was found between men and women in the association of poor-quality employment with poor health. We discuss the importance of institutional perspectives to understand work as a gendered experience that impacts health. We suggest more comprehensive welfare regime typologies that recognize women both as caregivers and workers. Expanding the scope of research on work and health to include this integrated view of life could make a stride toward gender health equity.

    • Occupational Safety and Health - Mining
      1. The human factors of mineworker fatigue: An overview on prevalence, mitigation, and what's nextexternal icon
        Bauerle TJ, Sammarco JJ, Dugdale ZJ, Dawson D.
        Am J Ind Med. 2021 Oct 20.
        BACKGROUND: Though mining remains a vital shiftwork industry for U.S. commerce, problems of continued prevalence of mineworker fatigue and its mitigation persist. Publications and reports on fatigue in mining appear to be rich and diverse, yet variable and remote, much like the industry itself. METHODS: The authors engaged in a brief nonexhaustive overview of the literature on sleep and fatigue among mineworking populations. RESULTS: This overview covers: potential sources of fatigue unique to mine work (e.g., monotonous and disengaging Work Tasks, underground environments and light exposure, remote work operations); evaluation of mitigation strategies for mineworker fatigue or working hours (e.g., shift-scheduling and training); and areas for future research and practice (e.g., fatigue risk management systems in mining, mineworker sleep and fatigue surveillance, lighting interventions, and automation). CONCLUSIONS: Fatigue continues to be a critical challenge for the mining industry. While research on the problems and solutions of mineworker fatigue has been limited to date, the future of fatigue research in mining can expand these findings by exploring the origins, nature, and outcomes of fatigue using advancements in lighting, automation, and fatigue risk management.

    • Parasitic Diseases
      1. Evidence supporting deployment of next generation insecticide treated nets in Burkina Faso: bioassays with either chlorfenapyr or piperonyl butoxide increase mortality of pyrethroid-resistant Anopheles gambiaeexternal icon
        Hien AS, Soma DD, Maiga S, Coulibaly D, Diabaté A, Belemvire A, Diouf MB, Jacob D, Koné A, Dotson E, Awolola TS, Oxborough RM, Dabiré RK.
        Malar J. 2021 Oct 18;20(1):406.
        BACKGROUND: Pyrethroid resistance poses a major threat to the efficacy of insecticide-treated nets (ITNs) in Burkina Faso and throughout sub-Saharan Africa, particularly where resistance is present at high intensity. For such areas, there are alternative ITNs available, including the synergist piperonyl butoxide (PBO)-based ITNs and dual active ingredient ITNs such as Interceptor G2 (treated with chlorfenapyr and alpha-cypermethrin). Before deploying alternative ITNs on a large scale it is crucial to characterize the resistance profiles of primary malaria vector species for evidence-based decision making. METHODS: Larvae from the predominant vector, Anopheles gambiae sensu lato (s.l.) were collected from 15 sites located throughout Burkina Faso and reared to adults for bioassays to assess insecticide resistance status. Resistance intensity assays were conducted using WHO tube tests to determine the level of resistance to pyrethroids commonly used on ITNs at 1×, 5 × and 10 × times the diagnostic dose. WHO tube tests were also used for PBO synergist bioassays with deltamethrin and permethrin. Bottle bioassays were conducted to determine susceptibility to chlorfenapyr at a dose of 100 µg/bottle. RESULTS: WHO tube tests revealed high intensity resistance in An. gambiae s.l. to deltamethrin and alpha-cypermethrin in all sites tested. Resistance intensity to permethrin was either moderate or high in 13 sites. PBO pre-exposure followed by deltamethrin restored full susceptibility in one site and partially restored susceptibility in all but one of the remaining sites (often reaching mortality greater than 80%). PBO pre-exposure followed by permethrin partially restored susceptibility in 12 sites. There was no significant increase in permethrin mortality after PBO pre-exposure in Kampti, Karangasso-Vigué or Mangodara; while in Seguenega, Orodara and Bobo-Dioulasso there was a significant increase in mortality, but rates remained below 50%. Susceptibility to chlorfenapyr was confirmed in 14 sites. CONCLUSION: High pyrethroid resistance intensity in An. gambiae s.l. is widespread across Burkina Faso and may be a predictor of reduced pyrethroid ITN effectiveness. PBO + deltamethrin ITNs would likely provide greater control than pyrethroid nets. However, since susceptibility in bioassays was not restored in most sites following pre-exposure to PBO, Interceptor G2 may be a better long-term solution as susceptibility was recorded to chlorfenapyr in nearly all sites. This study provides evidence supporting the introduction of both Interceptor G2 nets and PBO nets, which were distributed in Burkina Faso in 2019 as part of a mass campaign.

      2. In vivo efficacy and safety of artemether-lumefantrine and amodiaquine-artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018external icon
        Nhama A, Nhamússua L, Macete E, Bassat Q, Salvador C, Enosse S, Candrinho B, Carvalho E, Nhacolo A, Chidimatembue A, Saifodine A, Zulliger R, Lucchi N, Svigel SS, Moriarty LF, Halsey ES, Mayor A, Aide P.
        Malar J. 2021 Oct 2;20(1):390.
        BACKGROUND: Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether-lumefantrine (AL) and amodiaquine-artesunate (AS-AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. METHODS: The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000-200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS-AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. RESULTS: Totals of 368 and 273 patients were enrolled in the AL and AS-AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS-AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS-AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3-89.2%) for AL and 98.8% (95% CI 96.7-99.8%) for AS-AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6-99.2%) for AL and 99.6% (95% CI 97.9-100%) for AS-AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS-AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. CONCLUSION: Both AL and AS-AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration NCT04370977.

    • Substance Use and Abuse
      1. Trends in and Characteristics of Buprenorphine Misuse Among Adults in the USexternal icon
        Han B, Jones CM, Einstein EB, Compton WM.
        JAMA Netw Open. 2021 Oct 1;4(10):e2129409.
        IMPORTANCE: There is a lack of empirical research regarding misuse of buprenorphine hydrochloride. OBJECTIVE: To identify prescription opioids that are most frequently misused, assess differences in motivations for misuse between buprenorphine and nonbuprenorphine prescription opioids, and examine trends in and factors associated with buprenorphine misuse among individuals with or without opioid use disorder (OUD). DESIGN, SETTING, AND PARTICIPANTS: This survey study used nationally representative data on past-year prescription opioid use, misuse, OUD, and motivations for the most recent misuse from the 2015-2019 National Survey on Drug Use and Health (NSDUH). Participants included 214 505 civilian, noninstitutionalized adult NSDUH respondents. Data were collected from January 2015 to December 2019 and analyzed from February 15 to March 15, 2021. MAIN OUTCOMES AND MEASURES: Buprenorphine use, misuse, and OUD. Misuse was defined as use "in any way that a doctor [physician] did not direct you to use them, including (1) use without a prescription of your own; (2) use in greater amounts, more often, or longer than you were told to take them; or (3) use in any other way a doctor did not direct you to use them." RESULTS: The 214 505 respondents included in the analysis represented an estimated annual average 246.7 million US adults during 2015-2019 (51.7% [95% CI, 51.4%-52.0%] women; 13.9% [95% CI, 13.7%-14.1%] aged 18-25 y; 40.6% [95% CI, 40.3%-41.0%] aged 26-49 y; 45.5% [95% CI, 45.0-45.9%] aged ≥50 y). In 2019, an estimated 2.4 (95% CI, 2.2-2.7) million US adults used buprenorphine, and an estimated 0.7 (95% CI, 0.5-0.9) million misused buprenorphine compared with an estimated 4.9 (95% CI, 4.4-5.4) million and an estimated 3.0 (95% CI, 2.7-3.2) million who misused hydrocodone and oxycodone, respectively. Prevalence of OUD with buprenorphine misuse trended downward during the period from 2015 to 2019. "Because I am hooked" (27.3% [95% CI, 21.6%-33.8%]) and "to relieve physical pain" (20.5% [95% CI, 14.0%-29.0%]) were the most common motivations for the most recent buprenorphine misuse among adults with OUD. Adults who misused buprenorphine were more likely to report using prescription opioids without having their own prescriptions than those who misused nonbuprenorphine prescription opioids (with OUD: 71.8% [95% CI, 66.4%-76.6%] vs 53.2% [95% CI, 48.5%-57.8%], P < .001; without OUD: 74.7% [95% CI, 68.7%-79.9%] vs 60.0% [58.1%-61.8%], P < .001). Among adults with past-year OUD who used buprenorphine, multivariable multinomial logistic regression results indicated that buprenorphine misuse was associated with being 24 to 34 (adjusted odds ratio [AOR], 2.9 [95% CI, 1.4-5.8]) and 35 to 49 (AOR, 2.3 [95% CI, 1.2-4.5]) years of age, residing in nonmetropolitan areas (AOR, 1.8 [95% CI, 1.0-3.0]), and polysubstance use (eg, past-year prescription stimulant use disorder; AOR, 3.9 [95% CI, 1.3-11.2]) but was negatively associated with receiving treatment for drug use only (AOR, 0.4 [95% CI, 0.3-0.7]). CONCLUSIONS AND RELEVANCE: These findings suggest that among adults with OUD, prevalence of buprenorphine misuse trended downward from 2015 to 2019. In 2019, nearly three-fourths of US adults reporting past-year buprenorphine use did not misuse their prescribed buprenorphine, and most who misused reported using prescription opioids without having their own prescriptions. These findings underscore the need to pursue actions that expand access to buprenorphine-based OUD treatment, to develop strategies to monitor and reduce buprenorphine misuse, and to address associated conditions (eg, suicide risk, co-occurring mental illness, and polysubstance use).

    • Zoonotic and Vectorborne Diseases
      1. Clinical and Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever in Humans in Uganda, 2013-2019external icon
        Balinandi S, Whitmer S, Mulei S, Nyakarahuka L, Tumusiime A, Kyondo J, Baluku J, Mutyaba J, Mugisha L, Malmberg M, Lutwama J, Shoemaker T, Klena J.
        Am J Trop Med Hyg. 2021 Oct 18.
        Crimean-Congo Hemorrhagic Fever (CCHF) is endemic in Uganda, yet its epidemiology remains largely uncharacterized. To better understand its occurrence within Uganda, case reports of patients hospitalized with CCHF between 2013 and 2019 were reviewed. Further, genome sequences of CCHF-positive RNA obtained during this period were determined for phylogenetic comparisons. We found that a total of 32 cases (75% males; CFR, 31.2%), aged between 9 to 68 years, were reported during the study period. Most cases were detected during July to December of each outbreak year (81.2%; P < 0.01) and were located along the "cattle corridor" (68.7%, P = 0.03). The most common presenting symptoms were fever (93.8%), hemorrhage (81.3%), headache (78.1%), fatigue (68.8%), vomiting (68.8%), and myalgia (65.6%). In five patients for whom hematological data were available, varied abnormalities were observed including thrombocytopenia, leukopenia, anemia, lymphopenia, lymphocytosis, polycythemia, and microcytosis. About 56.3% (P = 0.47) of patients reported tick bites or exposure to livestock as their potential source of infection. Person-to-person transmission was suspected for two cases. Using unbiased metagenomics, we found that the viral S- and L- segments have remained conserved in Africa 2 clade since the 1950s. In contrast, the M segment split into two geographically interspersed clades; one that belongs to Africa 2 and another that is ancestral to Africa 1 and 2. Overall, this data summarizes information on the history and clinical presentation of human CCHF in Uganda. Importantly, it identifies vulnerable populations as well as temporal and geographic regions in Uganda where surveillance and control interventions could be focused.

      2. Perceptions of Health Care, Information, and Social Support Among Women Affected by Zika Virus Infection During Pregnancy in Two U.S. Statesexternal icon
        Squiers L, Brown S, Hauser K, Lynch M, Treiman K, Polen K, Amoozegar J, Quiroz R, Tong V, Waddell L, Gilboa S.
        Matern Child Health J. 2021 Oct 20.
        OBJECTIVES: To understand the information needs and experiences with health care and social support among women with confirmed or possible Zika virus infection during pregnancy. METHODS: We conducted in-depth interviews with 18 women whose pregnancies were part of surveillance efforts in two states, Pennsylvania and Virginia. Using a semi-structured guide available in English and Spanish, we asked women about their experiences. We conducted a thematic analysis using NVivo 11. RESULTS: Only one participant reported that her infant had been diagnosed with health problems related to congenital Zika virus infection. Most participants said they received the information they needed about Zika virus and their infant's medical care. Most participants primarily spoke Spanish and described satisfactory experiences communicating with providers, either using a mix of Spanish and English or using an interpreter. Coordination of care and clear communication among different providers was a key factor in participants' satisfaction with health care received. Participants noted high levels of stress around the uncertainty associated with Zika virus exposure during pregnancy. CONCLUSIONS FOR PRACTICE: Although participants reported satisfaction with care, they also reported high levels of anxiety and challenges coping with the uncertainties along their journeys. Study findings support the need for guidance for providers about how to talk with women about Zika virus infection during pregnancy and specifically how to discuss the uncertainties about diagnosis and outcomes.

      3. Leptospiral Infections in Humansexternal icon
        Haake DA, Galloway RL.
        Clinical Microbiology Newsletter. 2021 ;43(20):173-180.
        Leptospirosis is a globally widespread spirochetal infection spread from animals to humans. Infections are common in settings of endemicity, primarily in tropical regions of the world. Leptospirosis is typically a self-limited febrile illness but may progress to potentially fatal multiorgan system failure. Patients often present with a nonspecific acute febrile illness that is clinically difficult to distinguish from other similarly presenting infections endemic to tropical regions, including dengue fever, influenza, and malaria. A high index of suspicion is essential to early identification of patients who may benefit from antimicrobial therapy. Diagnostic testing is key to both recognition of early infection and outbreak investigation, typically in the setting of water exposure after heavy rainfall and flooding. This review focuses on the epidemiology, clinical manifestations, and laboratory diagnosis of leptospirosis, including nucleic acid amplification tests, culture, direct detection, and serological approaches. © 2021 Elsevier Inc.

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