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Adenoviruses are increasingly recognized as contributors to morbidity and mortality among stem cell and solid-organ transplant recipients. Clinical presentations range from asymptomatic viremia to respiratory and gastrointestinal disease, hemorrhagic cystitis, and severe disseminated illness. The limited clinical data available support the use of cidofovir for many of these illnesses. Prospective studies are needed to better understand the pathogenesis of and therapeutic options for adenoviral infections in this patient population.

Parainfluenza virus (PIV) is a negative-sense single-stranded RNA virus in the Paramyxoviridae family. There are 4 serotypes that follow seasonal patterns with varying rates of infection for each serotype. PIV is an established cause of disease and death in the pediatric and immunocompromised populations, and its impact on the hospitalized adult is becoming more apparent with the increased use of multiplex molecular assays in the clinical setting. The clinical presentation of PIV in hospitalized adults varies widely and includes upper respiratory tract infections, severe lower respiratory tract infections, and exacerbations of underlying disease; 0.2%–11.5% of hospitalized patients with pneumonia have been found to have PIV infection. Currently no licensed treatment is available for PIV infection. Ribavirin has been used, but case studies show no impact on mortality rates. DAS181, an inhaled sialidase, is undergoing clinical development for the treatment of PIV in adults and children.

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with the greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially in the United States (US) following the implementation of COVID-19-related non-pharmaceutical interventions but later rebounded with abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study from 2009 to 2023 in Chicago, Illinois, US, we examined RSV epidemiology, clinical severity, and genetic diversity. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings post-2020 and that hospitalized adults infected with RSV-A were at higher risk of intensive care admission than those with RSV-B. While population structures of RSV-A remained unchanged, RSV-B exhibited a genetic shift into geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development. Non-pharmaceutical interventions for COVID-19 also impacted the transmission of other viruses including respiratory syncytial virus (RSV). Here the authors describe the changing epidemiology, clinical severity, and genetic diversity of RSV in Chicago, Illinois, from July 2010 to April 2023.

ABSTRACTHuman respiratory syncytial virus (RSV) belongs to the recently defined Pneumoviridae family, Orthopneumovirus genus. It is a negative sense, single stranded RNA virus that results in epidemics of respiratory infections that typically peak in the winter in temperate climates and during the rainy season in tropical climates. Generally, one of the two genotypes (A and B) predominates in a single season, alternating annually, although regional variation occurs. RSV is a cause of disease and death in children, older people, and immunocompromised patients, and its clinical effect on adults admitted to hospital is clarified with expanded use of multiplex molecular assays. Among adults, RSV produces a wide range of clinical symptoms including upper respiratory tract infections, severe lower respiratory tract infections, and exacerbations of underlying disease. Here we discuss the latest evidence on the burden of RSV related disease in adults, especially in those with immunocompromise or other comorbidities. We review current therapeutic and prevention options, as well as those in development.

Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

The spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample. Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV). Dilution series produced the expected pattern of dose–response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % surrogate neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples. Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying inhibition of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.

Highly pathogenic avian influenza (HPAI) A(H5N1) emerged in 1997. 1 Since then, it has spread globally by migratory birds, resulting in infections in animals on every continent. HPAI A(H5N1) clade 2.3.4.4b emerged in 2021 and resulted in fatal infections in poultry as well as terrestrial and marine mammals. 1 In early 2024, influenza A infection was first recognized in dairy cows with mastitis in Texas. Infection in dairy cows is now widespread in the United States, affecting more than 875 herds in 16 states. Most cow infections are genotype B3.13, whereas most outbreaks in wild birds and poultry are genotype D1.1. Against . . .

On November 13–14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de‐risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.

The COVID-19 pandemic has disrupted the lives of millions and forced countries to devise public health policies to reduce the pace of transmission. In the Middle East and North Africa (MENA), falling oil prices, disparities in wealth and public health infrastructure, and large refugee populations have significantly increased the disease burden of COVID-19. In light of these exacerbating factors, public health surveillance is particularly necessary to help leaders understand and implement effective disease control policies to reduce SARS-CoV-2 persistence and transmission. The goal of this study is to provide advanced surveillance metrics, in combination with traditional surveillance, for COVID-19 transmission that account for weekly shifts in the pandemic speed, acceleration, jerk, and persistence to better understand a country's risk for explosive growth and to better inform those who are managing the pandemic. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. Using a longitudinal trend analysis study design, we extracted 30 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in MENA as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. The regression Wald statistic was significant (χ =859.5, P<.001). The Sargan test was not significant, failing to reject the validity of overidentifying restrictions (χ =16, P=.99). Countries with the highest cumulative caseload of the novel coronavirus include Iran, Iraq, Saudi Arabia, and Israel with 530,380, 426,634, 342,202, and 303,109 cases, respectively. Many of the smaller countries in MENA have higher infection rates than those countries with the highest caseloads. Oman has 33.3 new infections per 100,000 population while Bahrain has 12.1, Libya has 14, and Lebanon has 14.6 per 100,000 people. In order of largest to smallest number of cumulative deaths since January 2020, Iran, Iraq, Egypt, and Saudi Arabia have 30,375, 10,254, 6120, and 5185, respectively. Israel, Bahrain, Lebanon, and Oman had the highest rates of COVID-19 persistence, which is the number of new infections statistically related to new infections in the prior week. Bahrain had positive speed, acceleration, and jerk, signaling the potential for explosive growth. Static and dynamic public health surveillance metrics provide a more complete picture of pandemic progression across countries in MENA. Static measures capture data at a given point in time such as infection rates and death rates. By including speed, acceleration, jerk, and 7-day persistence, public health officials may design policies with an eye to the future. Iran, Iraq, Saudi Arabia, and Israel all demonstrated the highest rate of infections, acceleration, jerk, and 7-day persistence, prompting public health leaders to increase prevention efforts.

Influenza virus with resistance to antiviral drugs emerges with increased frequency in immunocompromised patients and can limit the benefit of M2 and neuraminidase (NA) inhibitors. We document 3 cases of influenza in severely immunocompromised patients from whom virus variants with molecular markers of resistance to anti-influenza drugs were recovered. Virus variants recovered from 2 patients had mutations in the M2, NA (with a previously recognized Glu119Val NA substitution), and hemagglutinin genes. We describe a novel Asp198Asn NA mutation in an influenza B virus and its decreased susceptibility to both oseltamivir and zanamivir