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The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients. [ABSTRACT FROM AUTHOR]

While we have the tools to achieve this goal, the persistent barriers to healthcare services experienced by too many individuals will need to be addressed to make significant progress and improve the health and quality of life of all people with human immunodeficiency virus (HIV). The necessary structural changes require actions by federal, state, and local policymakers and range from ensuring universal access to healthcare services to optimizing care delivery to ensuring a robust and diverse infectious diseases and HIV workforce. In this article, we outlines 10 key principles for policy reforms that, if advanced, would make ending the HIV epidemic in the United States possible and could have much more far-reaching effects in improving the health of our nation. [ABSTRACT FROM AUTHOR]

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revolutionized the practice of ambulatory medicine, triggering rapid dissemination of digital healthcare modalities, including synchronous video visits. However, social determinants of health, such as age, race, income, and others, predict readiness for telemedicine and individuals who are not able to connect virtually may become lost to care. This is particularly relevant to the practice of infectious diseases (ID) and human immunodeficiency virus (HIV) medicine, as we care for high proportions of individuals whose health outcomes are affected by such factors. Furthermore, delivering high-quality clinical care in ID and HIV practice necessitates discussion of sensitive topics, which is challenging over video without proper preparation. We describe the "digital divide," emphasize the relevance to ID and HIV practice, underscore the need to study the issue and develop interventions to mitigate its impact, and provide suggestions for optimizing telemedicine in ID and HIV clinics. [ABSTRACT FROM AUTHOR]

The goal of the Ending the HIV Epidemic Initiative is to reduce new infections in the United States by 90% by 2030. Success will require fundamentally changing human immunodeficiency virus (HIV) prevention and care delivery to engage more persons with HIV and at risk of HIV in treatment. While the coronavirus disease 2019 (COVID-19) pandemic reduced in-person visits to care facilities and led to concern about interruptions in care, it also accelerated growth of alternative options, bolstered by additional funding support. These included the use of telehealth, medication delivery to the home, and increased flexibility facilitating access to Ryan White HIV/AIDS Program services. While the outcomes of these programs must be studied, many have improved accessibility during the pandemic. As the pandemic wanes, long-term policy changes are needed to preserve these options for those who benefit from them. These new care paradigms may provide a roadmap for progress for those with other chronic health issues as well. [ABSTRACT FROM AUTHOR]

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists. To reduce the risk of medication-related errors, antiretroviral stewardship programs (ARVSPs) are needed to enhance patient safety. This call to action, endorsed by the Infectious Diseases Society of America, the HIV Medicine Association, and the American Academy of HIV Medicine, is modeled upon the success of antimicrobial stewardship programs now mandated by the Joint Commission. Herein, we propose definitions of ARVSPs, suggest resources for ARVSP leadership, and provide a summary of published, successful strategies for ARVSP that healthcare facilities may use to develop locally appropriate programs. [ABSTRACT FROM AUTHOR]

The recent Typhoid Fever Surveillance in Africa Program demonstrated an overall adjusted incidence of typhoid fever 2–3 times higher than previous estimates in Africa. Recently, a single-dose typhoid conjugate vaccine that allows infants as young as 6 months old to be vaccinated was prequalified by the World Health Organization (WHO). This Vi-based conjugate vaccine demonstrated robust immunogenicity after 1 dose in infants and children 6 through 23 months of age in India with no safety signal, and is currently being tested for the first time on the African continent in Malawi. The WHO Strategic Advisory Group of Experts recommends studies to evaluate co-administering Vi-typhoid conjugate vaccine (Vi-TCV) with routine childhood vaccines in typhoid-endemic countries. The Burkina Faso immunization schedule includes yellow fever vaccine (YFV) at 9 months and meningococcal A conjugate vaccine (MCV-A) at 15 months, in addition to measles-rubella vaccine at both 9 and 15 months. Co-administration testing of Vi-TCV with these routine vaccinations will provide the data needed to support large-scale uptake of Vi-TCV in sub-Saharan Africa. A randomized, controlled, Phase II trial of Vi-TCV co-administration with the vaccinations routinely given at 9 and 15 months of age is planned in Burkina Faso. The overall aim is to assess the safety and immunogenicity of Vi-TCV when co-administered with YFV at 9 months of age and with MCV-A at 15 months of age. A total of 250 participants (100 infants aged 9–11 months and 150 children aged 15–23 months) will be enrolled. Clinical Trials Registration. NCT03614533. [ABSTRACT FROM AUTHOR]

The recent Typhoid Fever Surveillance in Africa Program demonstrated an overall adjusted incidence of typhoid fever 2–3 times higher than previous estimates in Africa. Recently, a single-dose typhoid conjugate vaccine that allows infants as young as 6 months old to be vaccinated was prequalified by the World Health Organization (WHO). This Vi-based conjugate vaccine demonstrated robust immunogenicity after 1 dose in infants and children 6 through 23 months of age in India with no safety signal, and is currently being tested for the first time on the African continent in Malawi. The WHO Strategic Advisory Group of Experts recommends studies to evaluate co-administering Vi-typhoid conjugate vaccine (Vi-TCV) with routine childhood vaccines in typhoid-endemic countries. The Burkina Faso immunization schedule includes yellow fever vaccine (YFV) at 9 months and meningococcal A conjugate vaccine (MCV-A) at 15 months, in addition to measles-rubella vaccine at both 9 and 15 months. Co-administration testing of Vi-TCV with these routine vaccinations will provide the data needed to support large-scale uptake of Vi-TCV in sub-Saharan Africa. A randomized, controlled, Phase II trial of Vi-TCV co-administration with the vaccinations routinely given at 9 and 15 months of age is planned in Burkina Faso. The overall aim is to assess the safety and immunogenicity of Vi-TCV when co-administered with YFV at 9 months of age and with MCV-A at 15 months of age. A total of 250 participants (100 infants aged 9–11 months and 150 children aged 15–23 months) will be enrolled. Clinical Trials Registration. NCT03614533. [ABSTRACT FROM AUTHOR]

Innovations are urgently required for clinical development of antibacterials against multidrug-resistant organisms. Therefore, a European, public-private working group (STAT-Net; part of Combatting Bacterial Resistance in Europe [COMBACTE]), has reviewed and tested several innovative trials designs and analytical methods for randomized clinical trials, which has resulted in 8 recommendations. The first 3 focus on pharmacokinetic and pharmacodynamic modeling, emphasizing the pertinence of population-based pharmacokinetic models, regulatory procedures for the reassessment of old antibiotics, and rigorous quality improvement. Recommendations 4 and 5 address the need for more sensitive primary end points through the use of rank-based or time-dependent composite end points. Recommendation 6 relates to the applicability of hierarchical nested-trial designs, and the last 2 recommendations propose the incorporation of historical or concomitant trial data through Bayesian methods and/or platform trials. Although not all of these recommendations are directly applicable, they provide a solid, evidence-based approach to develop new, and established, antibacterials and address this public health challenge. [ABSTRACT FROM AUTHOR]

Background Global polio eradication efforts rely in part on molecular methods of detecting polioviruses, both wild and vaccine strains, from human and environmental samples. Previous assays used for detection of Sabin oral polio vaccine (OPV) in fecal samples have been labor and time intensive and vary in their sensitivity and specificity. Methods We developed a high-throughput, multiplex reverse-transcription quantitative polymerase chain reaction assay able to detect all 3 OPV strains in fecal samples. The assay used a KingFisher Duo Prime system for viral RNA isolation and extraction. Positive samples were retested and Sanger sequenced for verification of Sabin serotype identity. Results The 95% lower limit of detection was determined to be 3 copies per reaction for Sabin 1 and 3 and 4 copies per reaction for Sabin 2, with no cross-reactivity between the 3 serotypes and their primers. A total of 554 samples (3.6%) were positive, with 304 positive samples (54.9%) containing >1 serotype. Of the positive samples, 476 (85.9%) contained enough RNA to be sequenced, and of these all sequences were Sabin serotypes. The previous assay we used could process 48 samples in a 10-hour period, whereas the new assay processed >100 samples in 6 hours. Conclusions The new high-throughput, multiplex reverse-transcription quantitative polymerase chain reaction assay allowed for sensitive and specific detection of OPV serotypes while greatly decreasing sample handling and processing time. We were able to sequence 72.4% of the 210 positive samples in the cycle threshold range of 35–37. [ABSTRACT FROM AUTHOR]

An editorial is presented on the Clinical Infectious Diseases, Rhee and colleagues have presented the Infectious Diseases Society of America's (IDSA's) position paper outlining has proposed revisions to SEP-1, the U.S. first sepsis quality measure. Topics include SEP-1 the Centers for Medicare and Medicaid Services has signaled that early treatment of severe sepsis and septic shock is a national priority, and the measure was launched in 2015 because hospitalization rates for sepsis.

Background Human immunodeficiency virus (HIV)/AIDS and tuberculosis (TB) continue to be a significant global burden, disproportionately affecting low- and middle-income countries (LMICs). While much progress has been made in treating these epidemics, this has led to a rise in liver complications, as patients on ARTs and anti-TBs are at an increased risk of drug-induced liver injury (DILI). Therefore, patients on these medicines require consistent screening of liver function. Due to logistical barriers, gold standard DILI screening fails to be executed at the point-of-care in LMICs. For this reason, we used cost-effectiveness analysis to gauge the efficacy of a paper-test that could be implemented in these settings. Methods We used a Markov Model to simulate HIV and TB coinfected patient care in LMICs using both publicly available data and data from Village Health Works in Burundi. We compared the cost-effectiveness of two screening interventions for liver function monitoring: 1. paper-based point-of-care testing, and 2. gold-standard laboratory testing. These interventions were compared against baseline clinical monitoring. Results The paper test showed a 56% increase in efficacy over clinical monitoring alone. The paper-test is more cost-effective than the gold-standard method, at a ceiling cost of $1.60 per test. Conclusions With this information, policy makers can be informed as to the large potential value of paper-based tests when gold standard monitoring is not achievable. Scientists and engineers should also keep these analyses in mind and while in development limit the cost of an ALT screening test to $1.60. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Principles for Ending Human Immunodeficiency Virus (HIV) as an Epidemic in the United States: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association" which appeared in the August 15, 2022 issue.

The article reports that false vaccination papers of Eritrean migrants contributed to the yellow fever outbreak in Angola.

Globally, there are over 1 billion people infected with soil-transmitted helminths (STHs), mostly living in marginalized settings with inadequate sanitation in sub-Saharan Africa and Southeast Asia. The World Health Organization recommends an integrated approach to STH morbidity control through improved access to sanitation and hygiene education and the delivery of preventive chemotherapy (PC) to school-age children delivered through schools. Progress of STH control programs is currently estimated using a baseline (pre-PC) school-based prevalence survey and then monitored using periodical school-based prevalence surveys, known as Impact Assessment Surveys (IAS). We investigated whether integrating geostatistical methods with a Markov model or a mechanistic transmission model for projecting prevalence forward in time from baseline can improve IAS design strategies. To do this, we applied these 2 methods to prevalence data collected in Kenya, before evaluating and comparing their performance in accurately informing optimal survey design for a range of IAS sampling designs. We found that, although both approaches performed well, the mechanistic method more accurately projected prevalence over time and provided more accurate information for guiding survey design. Both methods performed less well in areas with persistent STH hotspots where prevalence did not decrease despite multiple rounds of PC. Our findings show that these methods can be useful tools for more efficient and accurate targeting of PC. The general framework built in this paper can also be used for projecting prevalence and informing survey design for other neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background Recent studies suggest that metformin use may be associated with improved infectious disease–related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia. Methods We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002–2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1. Results We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P <.003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P <.0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]:.86; 95% confidence interval [CI]:.78–.95) and 90-day (RR:.85; 95% CI:.79–.92) mortality was significantly lower for metformin users. Conclusions Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections. [ABSTRACT FROM AUTHOR]

Background Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective. Methods A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021. Results Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database. Conclusions HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear. Methods Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted. Results The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P <.001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods. Conclusions SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time. Clinical Trial Registration. NCT04510194. [ABSTRACT FROM AUTHOR]

Developing long-acting products and formulations for infectious diseases is a nontrivial undertaking that is frequently classified as high risk and low reward by the pharmaceutical industry. The Long-Acting/Extended Release Antiretroviral Research Resource Program (LEAP) was founded in 2015 with the support of the National Institutes of Health to encourage, promote, and accelerate the development of such products. Assessment methodology for any new proposal brought to this group is part of a framework—the LEAP Process—that includes a landscape analysis of what is currently available in the public domain. This is followed by in silico modeling and simulation offered as a service to the relevant scientific community. A variety of preclinical and clinical outcome metrics are applied to each new agent as part of a continuous feedback loop to improve product characteristics. This allows us to catalog knowledge gaps and barriers that can be addressed by engaged stakeholders. Results are communicated in scientific articles, reviews, and position papers. This undertaking serves to de-risk discovery, development, and implementation by bridging the gaps between academic, regulatory, and industrial investigators, and by engaging those in the community who will be the eventual users of these medicines. The LEAP Process has supported formulations now approved for human immunodeficiency virus, as well as products in clinical and preclinical development for tuberculosis and hepatitis viruses B and C. [ABSTRACT FROM AUTHOR]

A positive follow-up blood culture for methicillin-resistant Staphylococcus aureus (MRSA) while on seemingly appropriate therapy is a common and ominous development. However, the definition and management of persistent MRSA bacteremia is unstandardized. In this Opinion Paper, we identify the presence of bacteremia for > 1 calendar day as a "worry point" that should trigger an intensive diagnostic evaluation to identify metastatic infection sites. Next, we define the duration of MRSA bacteremia that likely constitutes antibiotic failure and outline a potential management algorithm for such patients. Finally, we propose pragmatic clinical trial designs to test treatment strategies for persistent MRSA bacteremia. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata. Project metadata constituted information collected to map out data sources and assess data quality, while facility data referred to the retrospective data collected from healthcare facilities. A down-selection process, labelled "the funnel approach" by the project, was adopted to use the project metadata in prioritizing and selecting laboratories for retrospective AMR data collection. Moreover, the metadata served as a guide for understanding the AMR data once they were collected. The findings from CAPTURA's metadata add to the current discourse on the limitation of AMR data in LMICs. There is generally a low volume of AMR data generated as there is a lack of microbiology laboratories with sufficient antimicrobial susceptibility testing capacity. Many laboratories in Asia are still capturing data on paper, resulting in scattered or unused data not readily accessible or shareable for analyses. There is also a lack of clinical and epidemiological data captured, impeding interpretation and in-depth understanding of the AMR data. CAPTURA's experience in Asia suggests that there is a wide spectrum of capacity and capability of microbiology laboratories within a country and region. As local AMR surveillance is a crucial instrument to inform context-specific measures to combat AMR, it is important to understand and assess current capacity-building needs while implementing activities to enhance surveillance systems. [ABSTRACT FROM AUTHOR]

Background In 2015, the UK government established the Fleming Fund with the aim to address critical gaps in surveillance of antimicrobial resistance (AMR) in low- and middle-income countries in Asia and Africa. Among a large portfolio of grants, the Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was awarded with the specific objective of expanding the volume of historical data on AMR, consumption (AMC), and use (AMU) in the human healthcare sector across 12 countries in South and Southeast Asia. Methods Starting in early 2019, the CAPTURA consortium began working with local governments and >100 relevant data-holding facilities across the region to identify, assess for quality, prioritize, and subsequently retrieve data on AMR, AMC, and AMU. Relevant and shared data were collated and analyzed to provide local overviews for national stakeholders as well as regional context, wherever possible. Results From the vast information resource generated on current surveillance capacity and data availability, the project has highlighted gaps and areas for quality improvement and supported comprehensive capacity-building activities to optimize local data-collection and -management practices. Conclusions The project has paved the way for expansion of surveillance networks to include both the academic and private sector in several countries and has actively engaged in discussions to promote data sharing at the local, national, and regional levels. This paper describes the overarching approach to, and emerging lessons from, the CAPTURA project, and how it contributes to other ongoing efforts to strengthen national AMR surveillance in the region and globally. [ABSTRACT FROM AUTHOR]

In response to the global threat of antimicrobial resistance (AMR), the Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project worked with microbiology laboratories, pharmacies, and local governments in South Asia and Southeast Asia to expand the volume of historical and current data available on AMR and antimicrobial use and to identify gaps in data and areas for quality improvement. When the CAPTURA project completed its country-level engagement in the first half of 2022, the consortium brought together local, regional, and global AMR stakeholders for a virtual regional workshop to review data outputs from the project and share strategies to inform national and regional efforts to combat AMR. This paper summarizes the main topics presented in the workshop held from 28 to 30 June 2022. As such, it highlights lessons learned from the project and strategies to fight AMR. Although CAPTURA has been invaluable to countries and information from the project is already being used, barriers concerning data quality and sharing remain. Regional-level initiatives should continue to build on the momentum gained from the CAPTURA project in supporting national-level surveillance and data quality improvements to inform critical decisions around planning, policies, and clinical care. Project findings have highlighted that issues with antimicrobial resistance and use are wide ranging across countries. Going forward, building on the current foundations and tailoring approaches to meet local needs and capacities will be fundamental in combatting AMR. [ABSTRACT FROM AUTHOR]

The increasing trends in antimicrobial resistance (AMR) continue to pose a significant threat to human health, with grave consequences in low- and middle-income countries. In collaboration with local governments and microbiology laboratories in South Asian and Southeast Asian countries, the Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project worked to identify gaps and expand the volume of existing AMR data to inform decision-makers on how to best strengthen their national AMR surveillance capacity. This article describes overall project management processes and the strategies implemented to address the disruptive impact of the coronavirus disease 2019 (COVID-19) pandemic on the project activities across diverse contexts in different countries. Also, it assesses in-country team's feedback on the conduct of activities and their overall impact on project completion. The strategies employed were tailored to the specific context of each country and included increased communication and collaboration among consortium partners and in-country teams, as well as hiring of additional in-country team members. This paper highlights the importance of local representation and capacities as well as real-time (virtual) engagement with stakeholders, ensuring close monitoring of the local situation and ability to tailor context-specific mitigation strategies to continue project implementation during disruptive external circumstances. [ABSTRACT FROM AUTHOR]

In high-income countries that were first to roll out coronavirus disease 2019 (COVID-19) vaccines, older adults have thus far usually been prioritized for these vaccines over younger adults. Age-based priority primarily resulted from interpreting evidence available at the time, which indicated that vaccinating the elderly first would minimize COVID-19 deaths and hospitalizations. The World Health Organization counsels a similar approach for all countries. This paper argues that some low- and middle-income countries that are short of COVID-19 vaccine doses might be justified in revising this approach and instead prioritizing certain younger persons when allocating current vaccines or future variant-specific vaccines. [ABSTRACT FROM AUTHOR]

Background Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures. Methods We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted. Results Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission. Conclusions Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19. [ABSTRACT FROM AUTHOR]

The article discusses the pathogenesis, clinical investigation, medical microbiology, diagnosis, immune mechanisms, and treatment of diseases caused by infectious agents.

To prepare for the development of the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections treatment guidelines, the CDC convened a committee of expert consultants in June 2019 to discuss recent abstracts and published literature on the epidemiology, diagnosis, and management of sexually transmitted infections.This paper summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults that were reviewed and discussed for consideration in developing the guidelines. The evidence reviewed mostly focused on efficacy of doxycycline and azithromycin for urogenital, rectal, and oropharyngeal CT infection, CT risk factors in women, performance of CT nucleic acid amplification tests on self-collected meatal specimens in men, and performance of newer CT point-of-care tests. [ABSTRACT FROM AUTHOR]

This paper is a call to action for the policies necessary to reduce the burden of antimicrobial resistance, including federal investments in antibiotic stewardship, antibiotic innovation, surveillance, research, diagnostics, infection prevention, the infectious diseases workforce, and global coordination. [ABSTRACT FROM AUTHOR]

The global burden of Group B Streptococcus (GBS) was estimated for 2015 prompting inclusion of GBS as a priority in the Global Meningitis Roadmap. New estimates for the year 2020 and a WHO report analysing the full value of GBS maternal vaccines has been launched to advance evidence based decision making for multiple stakeholders. In this first of a 10-article supplement, we discuss the following (1) gaps in evidence and action, (2) new evidence in this supplement, and (3) what actions can be taken now and key research gaps ahead. We call for investment in the research pipeline, notably description, development, and delivery, in order to accelerate progress and address the large burden of GBS for every family in every country. [ABSTRACT FROM AUTHOR]

Background This study is part of a multicountry matched-cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI) of children exposed to invasive group B Streptococcus (iGBS). The specific objective of this paper is to compare NDI across domains of iGBS survivors with a matched non iGBS group in our population. Methods Survivors of iGBS in a South Indian hospital were identified and recruited between January 2020 and April 2021. Cases were compared with age- and gender-matched non iGBS children. Participants were assessed using Bayley Scales of Infant and Toddler Development–3rd edition (BSID-III), Wechsler Preschool and Primary Scale of Intelligence–4th edition (WPPSI-IV), Wechsler Intelligence Scale for Children–5th edition (WISC-V), Child Behavior Checklist (CBCL), and Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2), depending on age. Results Our cohort comprised 35 GBS-exposed and 65 matched non iGBS children, aged 1–14 years. The iGBS-exposed group had 17 (48.6%) children with impairment in ≥1 domain compared to 25 (38%) in the non iGBS group (unadjusted OR, 1.51; 95% CI,.65–3.46), 9 (26%) children with "multi-domain impairment" compared to 10 (15.4%) in the non iGBS group (unadjusted OR, 1.90; 95% CI,.69–5.24), and 1 (2.9%) child with moderate to severe impairment compared to 3 (4.6%) in the non iGBS group (unadjusted OR,.60; 95% CI,.06–6.07). In the iGBS group, more children had motor impairments compared with the non iGBS group (unadjusted OR, 10.7; 95% CI, 1.19–95.69; P  = .034). Conclusions Children with iGBS seem at higher risk of developing motor impairments compared with a non iGBS group. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is considered a global threat, and novel drug discovery needs to be complemented with systematic and standardized epidemiological surveillance. Surveillance data are currently generated using phenotypic characterization. However, due to poor scalability, this approach does little for true epidemiological investigations. There is a strong case for whole-genome sequencing (WGS) to enhance the phenotypic data. To establish global AMR surveillance using WGS, we developed a laboratory implementation approach that we applied within the NIHR Global Health Research Unit (GHRU) on Genomic Surveillance of Antimicrobial Resistance. In this paper, we outline the laboratory implementation at 4 units: Colombia, India, Nigeria, and the Philippines. The journey to embedding WGS capacity was split into 4 phases: Assessment, Assembly, Optimization, and Reassessment. We show that on-boarding WGS capabilities can greatly enhance the real-time processing power within regional and national AMR surveillance initiatives, despite the high initial investment in laboratory infrastructure and maintenance. Countries looking to introduce WGS as a surveillance tool could begin by sequencing select Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens that can demonstrate the standardization and impact genome sequencing has in tackling AMR. [ABSTRACT FROM AUTHOR]

Background We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. Methods We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. Results We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens. Conclusions Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential. [ABSTRACT FROM AUTHOR]

The article explores a new specimen for syphilis diagnosis: evidence of high loads of Treponema pallidum DNA in saliva" , describes the polymerase chain reaction (PCR) detection of Treponema pallidum in blood and saliva specimens collected prior to treatment in patients with syphilis. The paper serves to validate and expand prior observations by Golden et al describing detection of T. pallidum in pharyngeal swab specimens.

This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the COVID-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue, and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions. [ABSTRACT FROM AUTHOR]

Responding to measles outbreaks in the United States puts a considerable strain on public health resources, and limited research exists about the effectiveness of containment strategies. In this paper we quantify the impact of isolation, contact tracing, and exclusion in reducing transmission during a measles outbreak in an under-vaccinated community. [ABSTRACT FROM AUTHOR]

Background The bacille Calmette-Guérin (BCG) tuberculosis vaccine has immunity benefits against respiratory infections. Accordingly, it has been hypothesized to have a protective effect against coronavirus disease 2019 (COVID-19). Recent research found that countries with universal BCG childhood vaccination policies tend to be less affected by the COVID-19 pandemic. However, such ecological studies are biased by numerous confounders. Instead, this paper reports on a rare nationwide natural experiment that occurred in Sweden in 1975, where discontinuation of newborns' BCG vaccination led to a dramatic decrease in BCG coverage rate, thus allowing us to estimate BCG's effect without the biases associated with cross-country comparisons. Methods Numbers of COVID-19 cases and hospitalizations were recorded for birth cohorts born just before and just after 1975, representing 1 026 304 and 1 018 544 individuals, respectively. We used regression discontinuity to assess the effect of BCG vaccination on COVID-19–related outcomes. On such a large population, this method allows for a precision that would be hard to achieve using a randomized controlled trial. Results The odds ratios (95% CI) for COVID-19 cases and COVID-19–related hospitalizations were 1.0005 (.8130–1.1881) and 1.2046 (.7532–1.6560), allowing us to reject fairly modest effects of universal BCG vaccination. We can reject with 95% confidence that universal BCG vaccination reduces the number of cases by 19% and the number of hospitalizations by 25%. Conclusions While the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19 among middle-aged individuals. [ABSTRACT FROM AUTHOR]

Orally-transmitted acute Chagas disease (CD) is emerging as an important public health problem. The prognosis of acute infection following oral transmission is unknown. The aim of this study was to analyze and summarize data on orally-transmitted acute CD. We searched for publications from 1968 to 31 January 2018. We included studies and unpublished data from government sources that reported patients with acute orally-transmitted CD. We identified 41 papers and we added 932 unpublished cases. In all, our study covered 2470 cases and occurrence of 97 deaths. Our meta-analysis estimated that the case-fatality rate was 1.0% (95% CI 0.0–4.0%). Lethality rates have declined over time (P  = .02). In conclusion, orally-transmitted acute CD has considerable lethality in the first year after infection. The lethality in symptomatic cases is similar to that from other routes of infection. The lethality rate of orally-acquired disease has declined over the years. [ABSTRACT FROM AUTHOR]

Background In October 2015, 65 people came into direct contact with a healthcare worker presenting with a late reactivation of Ebola virus disease (EVD) in the United Kingdom. Vaccination was offered to 45 individuals with an initial assessment of high exposure risk. Methods Approval for rapid expanded access to the recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) vaccine as an unlicensed emergency medicine was obtained from the relevant authorities. An observational follow-up study was carried out for 1 year following vaccination. Results Twenty-six of 45 individuals elected to receive vaccination between 10 and 11 October 2015 following written informed consent. By day 14, 39% had seroconverted, increasing to 87% by day 28 and 100% by 3 months, although these responses were not always sustained. Neutralizing antibody responses were detectable in 36% by day 14 and 73% at 12 months. Common side effects included fatigue, myalgia, headache, arthralgia, and fever. These were positively associated with glycoprotein-specific T-cell but not immunoglobulin (Ig) M or IgG antibody responses. No severe vaccine-related adverse events were reported. No one exposed to the virus became infected. Conclusions This paper reports the use of the rVSV-ZEBOV vaccine given as an emergency intervention to individuals exposed to a patient presenting with a late reactivation of EVD. The vaccine was relatively well tolerated, but a high percentage developed a fever ≥37.5°C, necessitating urgent screening for Ebola virus, and a small number developed persistent arthralgia. [ABSTRACT FROM AUTHOR]

The article explores article by Wright et al entitled "Imaging a Fever—Redefining the Role of 18FDG-PET/CT in FUO Investigations". The paper aims at providing an overview of the clinical benefits and cost-effectiveness of 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18FDG-PET/CT) in the investigation of fever of unknown origin (FUO).

Background Increasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex practices and associated drug use remain poorly understood. Methods Forty-seven patients with HCV were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was excluded by guaiac paper test. Risk behavior was assessed by standardized questionnaires. Results Median age was 41.9 years, 89% were HIV positive (+) (42/47) and 85% (40/47) were male, 58% (23/40) of whom were MSM. Acute HCV infection was diagnosed in 32% (15/47) ,with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had ≥1 HCV+ swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal), and contamination with blood was excluded in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 [IQR, 0.85] log IU/mL vs 4.08 [2.45] log IU/mL; P <.001). Using ROC-curve analysis, serum HCV-RNA cutoffs for ruling in/out any HCV+SS were established at 6.02 log IU/mL and 4.02 log IU/mL, respectively. Conclusions HCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex practices and sharing of nasal drug-sniffing "tools" might be important HCV transmission routes, especially in patients with high serum HCV-RNA. [ABSTRACT FROM AUTHOR]

The article highlights a study that distinguishes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome–related coronavirus (MERS-CoV). It discusses that the findings have pointed out how the viral load in COVID-19 is high at the very onset of the disease and then decreases over time, underlining the probability of a high load also in the presymptomatic phase.

We reviewed relevant syphilis diagnostic literature to address the question "What diagnostic considerations should be taken into account when screening for syphilis using the traditional or reverse algorithm?" Improved laboratory diagnosis of syphilis is an important element of the effort to reduce syphilis rates. Screening for syphilis is performed using either a nontreponemal or treponemal test (part of the traditional or reverse algorithm, respectively). Both syphilis algorithms are used by laboratories. However, there are limited data on the performance and cost-effectiveness of the algorithms. An expert panel generated "key questions" in the laboratory diagnosis of syphilis. This paper pertains to the key factors that should be considered when deciding whether to screen for syphilis using either the traditional or the reverse algorithm. A systematic literature review was performed, and tables of evidence were created to address this question. [ABSTRACT FROM AUTHOR]

We reviewed the relevant syphilis diagnostic literature to address the following question: what are the performance characteristics, stratified by the stage of syphilis, for nontreponemal serologic tests? The database search included key terms related to syphilis and nontreponemal tests from 1960–2017, and for data related to the venereal disease research laboratory test from 1940–1960. Based on this review, we report the sensitivity and specificity for each stage of syphilis (primary, secondary, early latent, late latent, or unknown duration; tertiary as well as neurosyphilis, ocular syphilis, and otic syphilis). We also report on reactive nontreponemal tests in conditions other than syphilis, false negatives, and automated nontreponemal tests. Overall, many studies were limited by their sample size, lack of clearly documented clinical staging, and lack of well-defined gold standards. There is a need to better define the performance characteristics of nontreponemal tests, particularly in the late stages of syphilis, with clinically well-characterized samples. Published data are needed on automated nontreponemal tests. Evidence-based guidelines are needed for optimal prozone titrations. Finally, improved criteria and diagnostics for neurosyphilis (as well as ocular and otic syphilis) are needed. [ABSTRACT FROM AUTHOR]