Leveraging lessons learned from the COVID-19 pandemic for HIV.

The rapid development of COVID-19 vaccines and their deployment in less than a year is an unprecedented scientific, medical, and public health achievement. This rapid development leveraged knowledge from decades of HIV/AIDS research and advances. However, the search for an HIV vaccine that would contribute to a durable end to the HIV pandemic remains elusive. Here, we draw from the US government experience and highlight lessons learned from COVID-19 vaccine development, which include the importance of public-private partnerships, equitable inclusion of populations impacted by the infectious pathogen, and continued investment in basic research. We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.

Low-Dose Radiation Therapy (LDRT) for COVID-19: Benefits or Risks?

The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide. This novel but unconventional use of radiation to treat COVID-19 prompted the National Cancer Institute, National Council on Radiation Protection and Measurements and National Institute of Allergy and Infectious Diseases to convene a workshop involving a diverse group of experts in radiation oncology, radiobiology, virology, immunology, radiation protection and public health policy. The workshop was held to discuss the mechanistic underpinnings, rationale, and preclinical and emerging clinical studies, and to develop a general framework for use in clinical studies. Without refuting or endorsing LDRT as a treatment for COVID-19, the purpose of the workshop and this review is to provide guidance to clinicians and researchers who plan to conduct preclinical and clinical studies, given the limited available evidence on its safety and efficacy.

Engineering immunity for next generation HIV vaccines: The intersection of bioengineering and immunology.

Bioengineering approaches grounded in immunology have the potential for the discovery and development of a successful HIV vaccine. The overarching goal is to engineer immunity through a fusion of immunology with bioengineering to create novel strategies for the design, development and delivery of vaccines based on the controlled modulation of the immune system. To foster these collaborations, the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Biomedical Imaging and Bioengineering (NIBIB) brought together a group of experts (see Table 1) from these diverse fields for a workshop in September 2018 to: (1) engage the engineering, immunology, and HIV vaccinology communities to dialogue on the topic of an HIV vaccine and; (2) generate a framework of new and innovative research avenues to explore in HIV vaccinology between knowledge stakeholders and problem solvers.

Innovative approaches to track lymph node germinal center responses to evaluate development of broadly neutralizing antibodies in human HIV vaccine trials.

Phase 1 clinical studies will soon evaluate novel HIV-1 envelope immunogens targeting distinct 'germline' and memory B cell receptors to ultimately elicit HIV-1 broadly neutralizing antibodies (bNAbs). The National Institute of Allergy and Infectious Diseases (NIAID) recently convened a panel of US-based expert scientists, clinicians, sponsors and ethicists to discuss the role of sampling draining lymph nodes within preventive HIV vaccine trials. The meeting addressed the importance of evaluating germinal center (GC) responses following immunization to predict bNAb potency and breadth, and reviewed key aspects of this procedure within the clinical research setting, including informed consent, adverse event monitoring, study participant acceptability, medical expertise and training. We review highlights from the meeting and discuss the advantages and disadvantages of sampling lymph nodes by excisional biopsies compared to fine needle aspirations (FNA) in the context of prophylactic HIV vaccine trials.

Invasive Streptococcus pneumoniae infection among hospitalized patients in Jingzhou city, China, 2010-2012.

BACKGROUND: Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China. METHODS: We conducted surveillance for IPD among children and adults from April 5, 2010 to September 30, 2012, in four major hospitals in Jingzhou City, Hubei Province. We collected demographic, clinical, and outcome data for all enrolled hospitalized patients with severe acute respiratory infection (SARI) or meningitis, and collected blood, urine, and cerebrospinal fluid (CSF) for laboratory testing for Sp infections. Collected data were entered into Epidata software and imported into SPSS for analysis. RESULTS: We enrolled 22,375 patients, including 22,202 (99%) with SARI and 173 (1%) with meningitis. One hundred and eighteen (118, 3%) with either SARI or meningitis were Sp positive, 32 (0.8%) from blood/CSF culture, and 87 (5%) from urine antigen testing. Of those 118 patients, 57% were aged ≥65 years and nearly 100% received antibiotics during hospitalization. None were previously vaccinated with 7-valent pneumococcal conjugate vaccine (PCV 7), 23-valent pneumococcal polysaccharide vaccine, or seasonal influenza vaccine. The main serotypes identified were 14, 12, 3, 1, 19F, 4, 5, 9V, 15 and 18C, corresponding to serotype coverage rates of 42%, 63%, and 77% for PCV7, PCV10, and PCV13, respectively. CONCLUSIONS: Further work is needed to expand access to pneumococcal vaccination in China, both among children and potentially among the elderly, and inappropriate use of antibiotics is a widespread and serious problem in China.

Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, China.

BACKGROUND: Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China. METHODS: We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza. RESULTS: During the study period, 15 354 children aged <15 years with signs and symptoms of SARI were enrolled at hospital admission. severe acute respiratory infection patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. P<.05). Only 16% (1116/7145) of enrolled patients had received seasonal trivalent influenza vaccination within 12 months of hospital admission. Non-vaccinated influenza cases were more likely than vaccinated influenza cases to have pneumonia (31/133, 23% vs 37/256, 15%, P<.05). severe acute respiratory infection cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared with SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, P<.05). CONCLUSIONS: Influenza A (H3N2) virus infection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children.

National Action Plan for Adverse Drug Event Prevention: Recommendations for Safer Outpatient Opioid Use.

INTRODUCTION: Adverse drug events (ADEs) have been highlighted as a major patient safety and public health challenge by the National Action Plan for Adverse Drug Event Prevention (ADE Action Plan), which was released by the Office of Disease Prevention and Health Promotion (ODPHP) in August 2014. The ADE Action Plan focuses on surveillance, evidence-based prevention, incentives, and oversights, additional research needs as well as possible measures and metrics to track progress of ADE prevention within three drug classes: anticoagulants, diabetes agents, and opioids.Objectives and Recommendations. With outpatient opioid prescriptions being a great concern among many healthcare providers, this article focuses on recommendations from the ADE Action Plan to help guide safer opioid use in healthcare delivery settings. Its aim is to discuss current federal methods in place to prevent opioid ADEs while also providing evidence to encourage providers and hospitals to innovate new systems and practices to increase prevention.

Epidemiology, Seasonality and Treatment of Hospitalized Adults and Adolescents with Influenza in Jingzhou, China, 2010-2012.

BACKGROUND: After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents. METHODS: We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0°C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012. RESULTS: Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients. CONCLUSIONS: There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China.

Adverse Drug Event Prevention: 2014 Action Plan Conference.

Adverse drug events (ADEs) have been highlighted as a national patient safety and public health challenge by the National Action Plan for Adverse Drug Event Prevention (ADE Action Plan), which was released by the Office of Disease Prevention and Health Promotion in August 2014. The following October, the ADE Prevention: 2014 Action Plan Conference provided an opportunity for federal agencies, national experts, and stakeholders to coordinate and collaborate in the initiative to reduce preventable ADEs. The single-day conference included morning plenary sessions focused on the surveillance, evidence-based prevention, incentives and oversights, and additional research needs of the drug classes highlighted in the ADE Action Plan: anticoagulants, diabetes agents, and opioids. Afternoon breakout sessions allowed for facilitated discussions on measures for tracking national progress in ADE prevention and the identification of opportunities to ensure safe and high-quality health care and medication use.

Racial and ethnic disparities in health care-associated Clostridium difficile infections in the United States: State of the science.

BACKGROUND: Among health care-associated infections (HAIs), Clostridium difficile infections (CDIs) are a major cause of morbidity and mortality in the United States. As national progress toward CDI prevention continues, it will be critical to ensure that the benefits from CDI prevention are realized across different patient demographic groups, including any targeted interventions. METHODS: Through a comprehensive review of existing evidence for racial/ethnic and other disparities in CDIs, we identified a few general trends, but the results were heterogeneous and highlight significant gaps in the literature. RESULTS: The majority of analyzed studies identified white patients as at increased risk of CDIs, although there is a very limited literature base, and many studies had significant methodological limitations. CONCLUSION: Key recommendations for future research are provided to address antimicrobial stewardship programs and populations that may be at increased risk for CDIs.

Interactive Web-Based Learning: Translating Health Policy Into Improved Diabetes Care.

In August 2014, the U.S. DHHS's Office of Disease Prevention and Health Promotion released the National Action Plan for Adverse Drug Event Prevention, highlighting prevention of diabetes agent-related hypoglycemia as a key area for improvement. In support of the Action Plan, the Office of Disease Prevention and Health Promotion then developed a web-based interactive module, or eLearning lesson, based on formative research and stakeholder feedback to educate healthcare professionals on strategies to prevent adverse drug events from diabetes agents. The training incorporates health literacy principles by demonstrating, through video scenarios, how to apply shared decision making when setting individualized glycemic targets, and how to use the teach-back method to confirm patients' understanding. Prior to release in September 2014, the training went through intensive usability testing and was pilot tested using a 36-item evaluation. Six months after its release (September 2014 to March 2015), the training landing page on health.gov had 24,334 unique page views. More than 90% of the 234 participants who earned continuing education credit agreed that they will be able to apply the knowledge gained from the lesson to their practice. Online trainings that model key prevention strategies are well received by health professional users and may play an important role in translating policy into improved outcomes.

Advancing Medication Safety: Establishing a National Action Plan for Adverse Drug Event Prevention.

BACKGROUND: Adverse drug events (ADEs) are important contributors to preventable morbidity and mortality, comprising one third of all hospital adverse events. In response to growing evidence detailing the high prevalence of ADEs, particularly among vulnerable older adults, Congress requested that the Secretary of the Department of Health and Human Services (HHS) convene a Federal Interagency Steering Committee to establish a National Action Plan to focus on ADE prevention. In August 2014, the Office of Disease Prevention and Health Promotion released the final version of the National Action Plan for Adverse Drug Event Prevention. The Action Plan directly supports the goals of the HHS Strategic Plan and the Patient Protection and Affordable Care Act by providing guidance on tracking and preventing ADEs, as well as describing evidence-based tools and resources to enhance medication safety. ADE ACTION PLAN CONTENT: The Federal Interagency Steering Committee focused the Action Plan on ADEs that are clinically significant, account for the greatest number of measurable harms as identified by using existing surveillance tools, and are largely preventable. As such, the decision was made to target three medication classes: anticoagulants, diabetes agents (insulin and oral hypoglycemic agents), and opioids. The Action Plan is organized around four key areas: surveillance; evidence-based prevention; payment, policy incentives, and oversight; and research opportunities to advance medication safety. CONCLUSION: One measure of the ADE Action Plan's success will be the wider dissemination of information and educational resources to providers and patients (or consumers) regarding the risks associated with medications. Future Action Plan iterations are likely to consider other high-priority medication classes and update the recommendations.

Response to challenge dose among young adults vaccinated for hepatitis B as infants: importance of detectable residual antibody to hepatitis B surface antigen.

OBJECTIVE: To determine whether a difference in antibody to hepatitis B surface antigen (anti-HBs) response to a hepatitis B vaccine challenge dose existed among persons with a baseline anti-HBs level of 0 mIU/mL (group 1) and those with "non-zero" levels of 0.1-4.9 (group 2) and 5.0-9.9 (group 3) mIU/mL, according to the VITROS ECi anti-HBs assay. DESIGN: Subanalysis of randomized clinical trial. Response was defined as a postchallenge anti-HBs level of at least 10 mIU/mL and 4-fold rise in anti-HBs level 2 weeks after a single challenge dose of 10 vs 20 µg Engerix-B. Baseline was defined as the anti-HBs level immediately before administration of the challenge dose. SETTING: Pediatric integrated healthcare system near Houston, Texas. PARTICIPANTS: Three hundred nineteen US-born 16-19-year-olds who completed the hepatitis B vaccine series during the first year of life. RESULTS: One hundred seventy-eight persons had zero (group 1) and 141 (114 group 2 and 27 group 3) had non-zero anti-HBs levels at baseline. Response to the challenge dose was significantly higher among those with non-zero vs zero anti-HBs levels, irrespective of challenge dosage; only 1 person with a non-zero anti-HBs level failed to respond to the challenge dose (group 3, 27/27 [100%] vs group 2, 113/114 [99%] vs group 1, 145/178 [82%]; P<.0001). CONCLUSIONS: Among participants with residual anti-HBs levels less than 10 mIU/mL 16-19 years after primary hepatitis B vaccination during infancy, non-zero anti-HBs levels, with rare exception, indicated persistence of immune memory to HBsAg. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01341275

Racial and Ethnic Disparities in Adverse Drug Events: A Systematic Review of the Literature.

The 2014 National Action Plan for Adverse Drug Event Prevention has recognized adverse drug events (ADEs) as a national priority in order to facilitate a nationwide reduction in patient harms from these events. Throughout this effort, it will be integral to identify populations that may be at particular risk in order to improve care for these patients. We have undertaken a systematic review to evaluate the evidence regarding racial or ethnic disparities in ADEs with particular emphasis on anticoagulants, diabetes agents, and opioids due to the clinical significance and preventability of ADEs associated with these medication classes. From an initial search yielding 3302 studies, we identified 40 eligible studies. Twenty-seven of these included studies demonstrated the presence of a racial or ethnic disparity. There was no consistent evidence for racial or ethnic disparities in the eight studies of ADEs in general. Asians were most frequently determined to be at higher risk of anticoagulant-related ADEs, and black patients were most frequently determined to be at higher risk for diabetes agents-related ADEs. Whites were most frequently identified as at increased risk for opioid-related ADEs. However, few of these studies were specifically designed to evaluate racial or ethnic disparities, lacking a standardized approach to racial/ethnic categorization as well as control for potential confounders. We suggest the need for targeted interventions to reduce ADEs in populations that may be at increased risk, and we suggest strategies for future research.

Duration of protection after infant hepatitis B vaccination series.

BACKGROUND: Little is known about duration of protection after the infant primary series of hepatitis B (HB) vaccine in settings of low HB endemicity. This study sought to determine the proportion of adolescents immunized as infants who had protective titers of antibody to hepatitis B surface antigen (anti-HBs) before and after a challenge dose of vaccine. METHODS: US-born 16- through 19-year-olds who received a recombinant HB vaccine 3-dose series initiated within 7 days of birth (group 1) or at ≥4 weeks of age (group 2) and completed by 12 months of age were enrolled. Participants had serologic testing before and 2 weeks after randomization to receive a challenge dose of 10 µg or 20 µg of Engerix-B. Baseline and postchallenge levels of anti-HBs were compared by group, challenge dosage, and demographic and behavioral characteristics. RESULTS: At baseline, 24% had protective anti-HBs levels of ≥10 IU/mL; 92% achieved protective levels after challenge dose. Although group 1 had a lower proportion of seroprotection at baseline, group and challenge dosage were not associated with postchallenge proportion of seroprotection. Being in group 2, higher test dosage, higher baseline geometric mean titer, and nonwhite race were associated with significantly higher geometric mean titer after challenge dose. CONCLUSIONS: More than 90% of study participants immunized against HB as infants exhibited a seroprotective response to a challenge dose of vaccine. Duration of protection from the primary infant HB vaccine series extended through the adolescent years in the setting of low HB endemicity.

Hepatitis B testing and access to care among racial and ethnic minorities in selected communities across the United States, 2009-2010.

UNLABELLED: Hepatitis B virus (HBV) infection is widely prevalent among racial and ethnic minorities in the United States; however, few data have been available regarding HBV testing and referral to care for these populations. Using survey data collected in 2009-2010 from the Racial and Ethnic Approaches to Community Health (REACH) across the U.S., we assessed rates and determinants of hepatitis B testing and access to care in 28 minority communities in the U.S. Of 53,896 respondents, 21,129 (39.2%) reported having been tested for hepatitis B. Of the 1,235 who reported testing positive, 411 (33.3%) reported currently receiving specialty care. After controlling for demographic and socioeconomic characteristics, the likelihood of having been tested for hepatitis B and receiving care if infected was higher among males, non-English speaking persons, and those having health insurance compared to their counterparts. Compared to college graduates, respondents without a college education were less likely to get tested for hepatitis B. CONCLUSION: These data indicate that more than half of racial/ethnic minority persons in these communities had not been tested for hepatitis B, and only about one-half of those who tested positive had ever received treatment. More state and federal efforts are needed to screen racial/ethnic minorities, especially foreign-born persons, for HBV and link those with infection to care.

Correction: The Increasing Burden of Imported Chronic Hepatitis B - United States, 1974-2008.

[This corrects the article DOI: 10.1371/journal.pone.0027717.].

Investigation of hepatitis B virus and human immunodeficiency virus transmission among severely mentally ill residents at a long term care facility.

BACKGROUND: A high prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections have been reported among persons with severe mental illness. In October, 2009, the Cook County Department of Public Health (CCDPH) initiated an investigation following notification of a cluster of HBV infections among mentally ill residents at a long term care facility (LTCF). METHODS: LTCF staff were interviewed and resident medical records were reviewed. Residents were offered testing for HBV, HCV, and HIV. Serum specimens from residents diagnosed with HBV or HIV infection were sent to the Centers for Disease Control and Prevention (CDC) for analysis. RESULTS: Eleven newly diagnosed HBV infections were identified among mentally ill residents at the LTCF. Of these 11 infections, 4 serum specimens were available for complete HBV genome sequencing; all 4 genomes were found to be closely related. Four newly diagnosed HIV infections were identified within this same population. Upon molecular analysis, 2 of 4 HIV sequences from these new infections were found to be nearly identical and formed a tight phylogenetic cluster. CONCLUSIONS: HBV and HIV transmission was identified among mentally ill residents of this LTCF. Continued efforts are needed to prevent bloodborne pathogen transmission among mentally ill residents in LTCFs.

An investigation of bloodborne pathogen transmission due to multipatient sharing of insulin pens.

On January 30, 2009, nursing staff at a military hospital in Texas reported that single-patient use insulin pens were used on multiple patients. An investigation was initiated to determine if patient-to-patient bloodbome transmission occurred from the practice. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) testing was offered to patients hospitalized from August 2007 to January 2009 and prescribed insulin pen injections. Virus from HCV-infected patients' sera was sequenced and compared for relatedness. An anonymous survey was administered to nurses. Of 2,113 patients prescribed insulin pen injections, 1,501 (71%) underwent testing; 6 (0.4%) were HIV positive, 6 (0.4%) were hepatitis B surface antigen positive, and 56 (3.7%) had HCV antibody. No viral sequences from 10 of 28 patients with newly diagnosed and 12 of 28 patients with preexisting HCV infection were closely related. Of 54 nurses surveyed, 74% reported being trained on insulin pen use, but 24% believed nurses used insulin pens on more than one patient. We found no clear evidence of bloodborne pathogen transmission. Training of hospital staff on correct use of insulin pens should be prioritized and their practices evaluated. Insulin pens should be more clearly labeled for single-patient use.

Prospects for prophylactic and therapeutic vaccines against hepatitis C virus.

Natural cross-protective immunity is induced after spontaneous clearance of primary hepatitis C virus (HCV) infection. Although this suggests that effective prophylactic vaccines against HCV are possible, there are still several areas that require further study. Current data indicate that, at best, vaccine-induced immunity may not completely prevent HCV infection but rather prevent persistence of the virus. However, this may be an acceptable goal, because chronic persistence of the virus is the main cause of pathogenesis and the development of serious liver conditions. Therapeutic vaccine development is also highly challenging; however, strategies have been pursued in combination with current or new treatments in an effort to reduce the costs and adverse effects associated with antiviral therapy. This review summarizes the current state of HCV vaccines and the challenges faced for future development and clinical trial design.