Searching for and utilizing biomedical data is an essential part of most research efforts, including in public health, and almost always involves use of major online databases. However, despite useful foundational guidance in the literature, developing and implementing unbiased and effective search strategies useful across multiple databases and sources remains challenging, with results highly dependent on the approaches used. Here, based on recent work searching for, extracting and analyzing geographically and scientifically diverse clinical and epidemiological antimicrobial resistance data, we discuss approaches we found useful to enhance each stage of the process and its outcomes. Recommendations include defining clear study goals to drive the data needs and scope, selecting appropriate databases, and creating and iteratively optimizing search terms and strategies. We also describe steps to manage the output of computerized searches, including the review of search outputs and the extraction of data, and discuss the potential use of unconventional data, including from manual searching and author queries, to supplement other available data. Taken together, the pragmatic approaches shared can help researchers enhance the yield and efficiency of their searches to produce more comprehensive, representative and useful datasets appropriate for their specific needs.

Abstract Background Carbapenem-resistant Enterobacterales are among the most serious antimicrobial resistance (AMR) threats. Emerging resistance to polymyxins raises the specter of untreatable infections. These resistant organisms have spread globally but, as indicated in WHO reports, the surveillance needed to identify and track them is insufficient, particularly in less resourced countries. This study employs comprehensive search strategies with data extraction, meta-analysis and mapping to help address gaps in the understanding of the risks of carbapenem and polymyxin resistance in the nations of Africa. Methods Three comprehensive Boolean searches were constructed and utilized to query scientific and medical databases as well as grey literature sources through the end of 2019. Search results were screened to exclude irrelevant results and remaining studies were examined for relevant information regarding carbapenem and/or polymyxin(s) susceptibility and/or resistance amongst E. coli and Klebsiella isolates from humans. Such data and study characteristics were extracted and coded, and the resulting data was analyzed and geographically mapped. Results Our analysis yielded 1341 reports documenting carbapenem resistance in 40 of 54 nations. Resistance among E. coli was estimated as high (> 5%) in 3, moderate (1–5%) in 8 and low (< 1%) in 14 nations with at least 100 representative isolates from 2010 to 2019, while present in 9 others with insufficient isolates to support estimates. Carbapenem resistance was generally higher among Klebsiella: high in 10 nations, moderate in 6, low in 6, and present in 11 with insufficient isolates for estimates. While much less information was available concerning polymyxins, we found 341 reports from 33 of 54 nations, documenting resistance in 23. Resistance among E. coli was high in 2 nations, moderate in 1 and low in 6, while present in 10 with insufficient isolates for estimates. Among Klebsiella, resistance was low in 8 nations and present in 8 with insufficient isolates for estimates. The most widespread associated genotypes were, for carbapenems, bla OXA-48, bla NDM-1 and bla OXA-181 and, for polymyxins, mcr-1, mgrB, and phoPQ/pmrAB. Overlapping carbapenem and polymyxin resistance was documented in 23 nations. Conclusions While numerous data gaps remain, these data show that significant carbapenem resistance is widespread in Africa and polymyxin resistance is also widely distributed, indicating the need to support robust AMR surveillance, antimicrobial stewardship and infection control in a manner that also addresses broader animal and environmental health dimensions.

This Viewpoint discusses H5 influenza vaccine use in light of the current outbreak and how vaccine development, stockpiling, and deployment could shape the US’ response to future pandemics.

The response to SARS-CoV-2 demonstrated the tremendous potential of investments in vaccine research and development to impact a global pandemic, resulting in the rapid development and deployment of lifesaving vaccines. However, this unprecedented speed was insufficient to either effectively combat initial waves of the pandemic or adapt in real time to new variants. This review focuses on opportunities from a public health oriented regulatory perspective for enhancing research, development, evaluation, production, and monitoring of safety and effectiveness to facilitate more rapid availability of pandemic influenza vaccines. We briefly review regulatory pathways and processes relevant to pandemic influenza, including how they can be strengthened and globally coordinated. We then focus on what we believe are critical opportunities to provide better approaches, tools, and methods to accelerate and improve vaccine development and evaluation and thus greatly enhance pandemic preparedness. In particular, for the improved vaccines needed to respond to a future influenza pandemic better and more rapidly, moving as much of the development and evaluation process as possible into the pre-pandemic period is critical, including through approval and use of analogous seasonal influenza vaccines with defined immune correlates of protection.

This Viewpoint examines the important role of the Food and Druf Administration (FDA) in facilitating the rapid development of coronavirus disease 2019 (COVID-19) vaccines.

Reassuring the Public and Clinical Community About the Scientific Review and Approval of a COVID-19 Vaccine

This Viewpoint lists 4 safeguards policy makers should consider before release of a COVID-19 vaccine, including ensuring effectiveness through clinical trials, providing evidence of safety, requiring informed consent before vaccination, and establishing comprehensive adverse effects monitoring systems.

This Viewpoint discusses the risks to patients and public health posed by the FDA's politically pressured Emergency Use Authorization (EUA) of chloroquine and hydroxychloroquine for COVID-19 treatment, and proposes principles to follow to ensure new therapies are studied properly and quickly to maximize benefits and minimize risks to patients.

Chenguang Shen, PhD; Zhaoqin Wang, PhD; Fang Zhao, PhD; Yang Yang, MD; Jinxiu Li, MD; Jing Yuan, MD; Fuxiang Wang, MD; Delin Li, PhD; Minghui Yang, PhD; Li Xing, MM; Jinli Wei, MM; Haixia Xiao, PhD; Yan Yang, MM; Jiuxin Qu, MD; Ling Qing, MM; Li Chen, MD; Zhixiang Xu, MM; Ling Peng, MM; Yanjie Li, MM; Haixia Zheng, MM; Feng Chen, MM; Kun Huang, MM; Yujing Jiang, MM; Dongjing Liu, MD; Zheng Zhang, MD; Yingxia Liu, MD; Lei Liu, MD

This Viewpoint offers provisional answers to common questions the public will have about approved COVID-19 vaccines, including what they can expect regarding its effectiveness and safety, trustworthiness of the approval process, and whether society can return to normal once sufficient numbers of people are immunized.

Reassuring the Public and Clinical Community About the Scientific Review and Approval of a COVID-19 Vaccine

Carbapenem-resistant Enterobacteriaceae infections have spread globally, leaving polymyxins, including colistin, as ‘last-resort treatments’. Emerging colistin resistance raises the spectre of untreatable infections. Despite this threat, data remain limited for much of the world, including Southeast Asia where only 3 of 11 nations submitted data on carbapenem and colistin resistance for recent World Health Organization (WHO) reports. To improve our understanding of the challenge, we utilised broad strategies to search for and analyse data on carbapenem and colistin resistance among Escherichia coli and Klebsiella in Southeast Asia. We found 258 studies containing 526 unique reports and document carbapenem-resistant E. coli and Klebsiella in 8 and 9 of 11 nations, respectively. We estimated carbapenem resistance proportions through meta-analysis of extracted data for nations with ≥100 representative isolates. Estimated resistance among Klebsiella was high (>5%) in four nations (Indonesia, Philippines, Thailand and Vietnam), moderate (1–5%) in two nations (Malaysia and Singapore) and low (<1%) in two nations (Cambodia and Brunei). For E. coli, resistance was generally lower but was high in two of seven nations with ≥100 isolates (Indonesia and Myanmar). The most common carbapenemases were NDM metallo-β-lactamases and OXA β-lactamases. Despite sparse data, polymyxin resistance was documented in 8 of 11 nations, with mcr-1 being the predominant genotype. Widespread presence of carbapenem and polymyxin resistance, including their overlap in eight nations, represents a continuing risk and increases the threat of infections resistant to both classes. These findings, and remaining data gaps, highlight the urgent need for sufficiently-resourced robust antimicrobial resistance surveillance.

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most difficult to treat emerging multidrug-resistant organisms. Major limitations exist in surveillance needed to address CRE, particularly in areas with inadequate resources. We utilised optimised strategies to search for data on carbapenem susceptibility of Klebsiella spp. and Escherichia coli from the World Health Organization (WHO) Africa Region. Core data elements were extracted for meta-analysis and mapping. Despite sparse data in existing reviews, 180 documents including 314 reports on susceptibility of E. coli and/or Klebsiella were located, providing information on 31 (66%) of 47 nations. Carbapenem-resistant E. coli or Klebsiella were identified in 22 (71%) of these 31 countries. Crude resistance proportions were estimated for nations with >100 representative isolates. Median resistance among E. coli was <1% in 11 (61%) of 18 nations meeting criteria, 1-5% in 6 nations (33%) and >5% in 1 nation (6%). For Klebsiella spp., corresponding figures were <1% in 10 (67%) of 15 nations, 1-5% in 3 nations (20%) and >5% in 2 nations (13%). Comprehensive, customised search strategies with analysis and mapping of defined data elements provide an enhanced view of carbapenem-resistant E. coli and Klebsiella in Africa. These CRE are widely distributed and are generally present at low to moderate levels. Whilst use of diverse and largely clinically derived data has limitations and cannot substitute for surveillance, it can enhance situational awareness. The approaches utilised can support improved risk understanding and prioritisation and may be applied to other micro-organisms and areas where surveillance remains inadequate.

Abstract Background Gene-based screening is a tool to detect and track multi-drug-resistant organisms (MDROs) in hospitalized patients. MDRO acquisition and colonization during the duration of a hospital stay and their persistence over time are not well described. Methods A peri-anal swab was collected within 48 hours of admission from patients on medical wards and the MICU at the Washington DC VA Medical Center and repeat swabs were obtained day 7 and 14 on patients consenting to participate. Clinical and laboratory data from admission to 12mo post discharge was reviewed. Genes associated with VRE (VanA), ESBL (CTX-M), carbapenase-producing organisms or CPOs (OXA-23, OXA-51) and CREs (KPC,NDM,VIM, IMP, OXA-48) were tested on swabs by the Acuitas-MDRO Test (OpGen, Inc.). Results Between July 2015 and August 2016, 565 hospitalized patients were screened with 210 swabs collected from 182 subjects. One swab was nonevaluable. Subjects had a mean age 67.5 ± 12.0 years (26–94 years, 38% ≥70 years) and 39% received empiric antibiotics at admission. Subjects were hospitalized for 1037 cumulative bed-days (1–81 days) with median LOS of 3 days; 84% (152/182) had a stay of a week or less. Among those who remained hospitalized long enough for serial testing, 45% were willing or able to provide >1 swab. Those with >1 swab were significantly older (+4.9 years, P = 0.03), more likely to have to have been admitted for an infectious diagnosis (48% vs. 24%, P = 0.02). All subjects negative for MDRO genes on admission with >1 swab remained negative on serial sampling. Sixteen subjects (8.8%) had one or more genes present on screening and all three with >1 swab had persistence of that gene on repeat sampling. Genes harbored included CTX-M (4.4%), VanA (4.4%), OXA-51(0.6%), KPC (0.6%). Conclusion The rate of occult MDRO colonization was low in our predominately elderly hospitalized patients. The majority of consenting participants were discharged before swabs could be repeated. Serial sampling revealed that results of swabs persisted over time in the same subject despite treatments received during hospitalization, including exposures to antibiotics. The identification of occult MDRO carriage during a hospitalization, even when obtained after admission, may have utility in guiding treatment for providers. Disclosures All authors: No reported disclosures.

We are unlikely, with current technologies, to have sufficient pandemic influenza vaccine ready in time to impact the first wave of the next pandemic. Emerging data show that prior immunization with an immunologically distinct hemagglutinin of the same subtype offers the potential to "prime" recipients for rapid protection with a booster dose, years later, of a vaccine then manufactured to match the pandemic strain. This article proposes making prepandemic priming vaccine(s) available for voluntary use, particularly to those at high risk of early occupational exposure, such as first responders and healthcare workers, and to others maintaining critical infrastructure. In addition to providing faster protection and potentially reducing social disruption, being able, early in a pandemic, to immunize those who had received prepandemic vaccine with one dose of the pandemic vaccine, rather than the 2 doses typically required, would reduce the total doses of pandemic vaccine then needed, extending vaccine supplies.

M. Colin Jordan, former Infectious Diseases Division Director and Professor of Medicine at both the University of Minnesota and the Oregon Health and Science University (OHSU), died April 8, 2015. Colin lived an exceptional life, touching patients and colleagues with his excellence and high expectations as a physician and scientist and his rare combination of warmth and nurturing with cutting, yet understated, humor. He did not talk much about his past, so few may know he was born in a bomb shelter in England in 1941, came to the United States aboard the Queen Elizabeth at age 6, and was signed by Walt Disney studios as a dancer at the age of 12. Colin was an accomplished college baseball player, and after graduation from Loyola Marymount he was offered a contract with the Los Angeles Angels; however, instead of becoming a baseball player, he decided to go into medicine. After medical school at Creighton, he trained at the University of Washington (UW), where he worked with many outstanding clinicians, including their stellar Infectious Diseases group and Bill Kirby, with whom he wrote one of his first papers. His time at UW helped inspire his career, including his becoming an Epidemic Intelligence Service (EIS) officer from 1970 to 1972. An early indication of both his talent and humor was his publication in the American Journal of Public Health, from an EIS investigation, entitled “Salmonellosis among restaurant patrons: the incisive role of a meat slicer”. After stints as a faculty member at UCLA and Davis, he became Division Chief at the University of Minnesota, serving from 1984 to 1998. At Minnesota, where I had the pleasure of working with him, he developed a strong multi-institution Division into a warm and collegial group. From 1998 to 2005, he served as Chief of ID and the first E.H. Cooley Professor of Medicine at OHSU. A staunch believer that scientifically well trained clinicians can provide important insights and have a major role in research, he made many contributions to the understanding of cytomegalovirus infection including, particularly, its transmissibility through sexual contact, murine models of disease, the biology of latency, resistance to antivirals, and molecular detection for diagnostic and research uses. Everywhere he served or led, he influenced students, other trainees, patients, and peers with not only his critical thinking as a scientist and clinician, but also his decency, fairness and compassion, and his low tolerance for puffery and pretension, the latter remarkable for an accomplished academician and almost as rare then as now. He helped motivate and propel many students and trainees into successful careers as physicians and scientists. As he watched medicine and science becoming a business, rather than the calling and commitment which he advocated for and lived by example, it's impossible to know whether Colin ever dreamed of again standing on a major league baseball field. In any case, to all whose lives he touched, he will always be seen as a Major League physician, scientist, and, most important, friend. He leaves his wife, Pamela Lahrs, his previous spouses, Bonnie Baskin and Patricia Jordan, daughters Teresa and Angela, son Colin Jr., and 4 grandchildren. Many fascinating aspects of his life and work, from that bomb shelter to academia, and of his generous personality are captured in his enjoyable book, “Briefings from a Doctor's Foxhole”. If desired, donations in his honor can be made to OSHU or the charity of your choice.

The report that two seriously ill U.S. volunteers received an experimental Ebola drug has raised questions around the globe. We need to think both carefully and humanistically about balancing access to investigational agents with the need for answers about what works.

There are many challenges in the clinical recognition, management, and treatment of patients with tick-borne diseases. The first and most important step for clinicians is to simply consider the possibility of a tick-borne infection in patients who, through their place of residence, occupational or recreational activities, or travels, may have been exposed to ticks that are vectors of human disease. In such a setting, considering the possibility of a tick-transmitted disease is critical because the disease manifestations are often both nonspecific and multisystemic, there are seldom definitive clinical or laboratory diagnostic findings present at the time of presentation, and the consequences of failure to treat can be fatal. As a result, prompt presumptive therapy is often appropriate and may, in fact, be lifesaving. This chapter provides an overview of differential diagnosis and points to consider related to certain clinical and laboratory manifestations of disease as well as empiric treatment. In addition to known tick exposure or bites in areas of endemicity, clinical findings particularly suggestive of a possible tick-borne infection may include leukopenia and/or thrombocytopenia and persistent fevers despite use of broad-spectrum antimicrobials, as well as negative routine cultures and the presence of otherwise unexplained skin rashes or lesions (particularly if petechial, hemorrhagic, or eschar) or central nervous system abnormalities.

The availability of a safe blood supply is critical for both medical progress and national security. Safety has been increased by nucleic acid–amplification testing, as documented by Stramer et al. in this issue of the Journal.1 As health care providers, public health officials, and providers and users of donated blood and tissues we strive to improve the safety of the blood supply and to consider future threats, including threats to the safety of the donated tissue supply.Twenty years ago — with tragic consequences — up to 1 in 100 blood units in the United States transmitted the human . . .