Background Clinical outcomes in bacterial bloodstream infections (BSI) are influenced by multiple factors, including bacterial species, host immunity, and antibiotic therapy. However, the mechanisms by which such factors influence outcomes and their potential biomarkers are poorly understood. We aimed to identify bacterial- and antibiotic-specific host transcriptional signatures in patients with bacterial

Background Cutavirus (CuV) is associated with mycosis fungoides; however, the CuV status in parapsoriasis en plaques (PP), a premalignant inflammatory condition of mycosis fungoides, has not been fully delineated. Methods Fifty-five Japanese patients with chronic inflammatory skin diseases, including 13 patients with PP, were studied. Results CuV DNA was detected significantly more frequently in biopsies

We explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) “snapshots” at a sentinel site within Lima, Peru for evaluating local transmission dynamics over time. Within a 17 km2 area, 15/70 (21%) isolates with WGS collected during 2011-2012 and 22/81 (27%) collected during 2020-2021 were clustered (p = 0.414), and additional isolates clustered with those from outside

The Los Angeles County Department of Public Health established a surveillance system to identify complicated (advanced HIV or hospitalized) mpox cases. From August 1st to November 30th, 2022, we identified 1,581 mpox cases of which 134 were complicated (8.5%). A subset of eight cases did not recover after either initiating or completing a course of oral tecovirimat. All eight patients were HIV positive

Variola virus (VARV), the etiological agent of smallpox, had enormous impacts on global health prior to its eradication. In the absence of global vaccination programs, monkeypox virus (MPXV) has become a growing public health threat that includes endemic regions of Sub-Saharan Africa and, more recently, non-endemic regions following the identification of clade IIb MPXV in many global regions. While

Background Variability in vaccine responsiveness among young children is poorly understood. Methods Nasopharyngeal secretions were collected in the first weeks of life for measurement of cytokines/chemokines seeking a biomarker, and blood samples collected at age one year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal (NVR) and high (HVR), to test for vaccine

Background Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized. Methods We randomly selected 3,284 of 12,845 samples collected

COVID-19 continues to be a global health concern and booster doses are necessary for maintaining vaccine-mediated protection, limiting the spread of SARS-CoV-2. Despite multiple COVID vaccine options, global booster uptake remains low. Reactogenicity, the occurrence of adverse local/systemic side effects, plays a crucial role in vaccine uptake and acceptance, particularly for booster doses. We conducted

We developed mathematical models to analyze a large dengue virus (DENV) epidemic in Reunion Island in 2018–2019. Our models captured major drivers of uncertainty including the complex relationship between climate and DENV transmission, temperature trends, and underreporting. Early assessment correctly concluded that persistence of DENV transmission during the austral winter 2018 was likely and that

Preexisting immunity against influenza viruses has long been known to regulate the magnitude and specificity of vaccine-induced humoral immunity. In this manuscript by Lu et al., the authors highlight how varying levels of preexisting antibodies against a single site on hemagglutinin impact vaccine-induced antibody responses. This commentary discusses the essential findings and implications of the

COVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat–containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed

Background Pre-existing immunity, including memory B-cells and pre-existing antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether pre-existing hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163-antibodies) could affect antibody responses following vaccination with A/California/07/2009-like

Background Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX-CoV2373), to assess antibody responses to SARS-CoV-2. Methods Participants aged 18 to 64 years immunized with 3 doses of prototype

Background Improved COVID-19 prevention is needed for immunocompromised individuals. Methods Prospective study of healthcare workers (HCW) and immunocompromised participants with baseline serology following 2 mRNA vaccines and who were retested after dose 3 (D3); multivariable regression was used to identify predictors of serological responses. IFNγ/TNFα T-cell responses were assessed in a subset.

Objective To develop next generation sequencing (NGS) techniques for Mpox viral clade and lineage analysis. Methods Mpox DNA was extracted from DCHHS patients using QIAamp DSP DNA Blood Mini Kit. The Mpox Sequencing workflow adapted Illumina’s COVIDSeq assay using hMpox primer pools from Yale School of Public Health. Sequencing steps started with amplifying cDNA amplicons, tagmentation, PCR indexing

There is an urgent need for new non-antibiotic based treatment strategies for Clostridioides difficile infection. C. difficile toxin B (TcdB) is a virulent factor that is essential for causing disease. Here, we investigated whether a survival-signaling pathway could protect against TcdB. We found significant increase in caspase-3 apoptotic activity in intestinal epithelial cells of mice exposed to

The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1–triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1–induced excessive proinflammatory cytokine production. Further experiments showed

Malnutrition, which continues to affect hundreds of millions of people worldwide, is both a cause and consequence of a range of infectious diseases. In this perspective piece, we provide an overview of the bidirectional relationship between malnutrition and infectious diseases. In addition to enteric infections, we use tuberculosis as a case study of this relationship between malnutrition and infectious

Background The non-classical antigen presentation molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells. Activation of these cells triggers a rapid cytokine response providing an interface between innate and adaptive immune responses. The importance of CD1d and iNKT cells in varicella zoster virus (VZV) infection has been emphasised by clinical reports of individuals with

Background Published studies about mRNA COVID-19 vaccine effects focus on younger individuals comprising the majority of workforce. However, studies about elderly adults are sparse. Methods 107 subjects (median 78 (IQR 58.5-90.5, range 35-105) yo) were recruited, and factors associated with antibody titer after the third mRNA COVID-19 vaccine were analyzed between 49 elderly (age ≥80, median 94 (IQR

Objective The objective of this study was to assess the clinical impact and outcome of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on children with cancer or who received a hematopoietic stem cell transplantation (HSCT). Study Design The Italian Association of Pediatric Hematology and Oncology (AIEOP) performed a nationwide, multicenter, observational cohort study, including

Introduction Globally, rotavirus infections are the most common cause of diarrhea-related deaths, especially among children under 5 years of age. This virus can be transmitted through the fecal-oral route, though zoonotic and environmental contributions to transmission are poorly defined. The purpose of this study is to determine the epidemiology of rotavirus in humans, animals, and the environment

Ebola virus (EBOV) disease is marked by rapid virus replication and spread. EBOV enters the cell by macropinocytosis and replicates in the cytoplasm, and nascent virions egress from the cell surface to infect neighboring cells. Here, we show that EBOV uses an alternate route to disseminate: tunneling nanotubes (TNTs). TNTs, an actin-based long-range intercellular communication system, allows for direct

Background While non-inferiority of tenofovir alafenamide and emtricitabine (TAF/FTC) as pre-exposure prophylaxis (PrEP) for the prevention of HIV has been shown, interest remains in its efficacy relative to placebo. We estimate the efficacy of TAF/FTC PrEP versus placebo for the prevention of HIV infection. Methods We used data from the DISCOVER and iPrEx trials to compare TAF/FTC to placebo. DISCOVER

Background A SARS-CoV-2 infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics. Methods From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and

Adaptive platform trials can be more efficient than classic trials for developing new treatments. Moving from culture-based to simpler- or faster-to-measure biomarkers as efficacy surrogates may enhance this advantage. We performed a systematic review of treatment efficacy biomarkers in adults with tuberculosis. Platform trials can span different development phases. We grouped biomarkers as: α, bacterial

Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox Clade IIb virus outbreak, we developed a 7-item mpox severity scoring system (MPOX-SSS) with initial variables refined based on data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in

HIV is associated with severe mpox. Sexually transmitted infections (STIs) could facilitate mpox transmission. We estimated HIV and STI frequency among patients with mpox, and compared characteristics associated with mpox severity. Mpox cases during June 1, 2022–March 31, 2023, were matched to Illinois HIV/AIDS surveillance data. Among 1,124 mpox patients, 489 (44%) had HIV and 786 (70%) had prior

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women’s Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% living with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining pre-menopausal

Background The "zero-dose" children are those without any routine vaccination or lacking the first dose of the diphtheria-tetanus-pertussis-containing vaccine. As per 2022 WHO/UNICEF estimates, globally, Nigeria has the highest number of zero-dose with over 2.3 million unvaccinated. Methods We used data from the 2021 Nigeria Multiple Indicator Cluster Survey – National Immunisation Coverage Survey

Extracellular vesicles (EVs) mediate intercellular communication by transporting proteins. To investigate the pathogenesis of Mycoplasma gallisepticum (MG), a major threat to the poultry industry, we isolated and characterized MG-produced EVs. Our study highlights the significant impact of MG-derived EVs on immune function and macrophage apoptosis, setting them apart from other MG metabolites. These

Respiratory syncytial virus (RSV) infection is a major cause of pneumonia in adults. Little is known on the viral genetic diversity and the associated clinical phenotypes in this population. In this single-center prospective cohort study, RSV-infected patients between January 2019 and December 2022 were included. Of 100 patients, including 41 with severe infection, 72 were infected with RSV-B. RSV

Neisseria gonorrhoeae establishes tight interactions with mucosal epithelia through activity of its type IV pilus, while pilus-retraction forces furthermore activate autophagic responses towards invading gonococci. Here we studied pilus-independent epithelial cell responses and showed that pilus-negative gonococci residing in early and late endosomes are detected and targeted by nucleotide-binding

The RTS, S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O-fucosylated on the sporozoite surface. We determined whether RTS, S/AS02A-induced IgGs recognise vaccine-like non-fucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS, S/AS02A vaccination induced high anti-PfCSP IgG levels associated with

BACKGROUND Delayed diagnosis and improper therapy for intraocular infections usually result in poor prognosis. Due to limitations of conventional culture and polymerase chain reaction methods, most causative pathogens cannot be identified from vitreous humor (VH) or aqueous humor (AH) samples with limited volume. METHODS Patients with suspected intraocular infections were enrolled from January 2019

Hepatitis C (HCV) remains a major public health problem, despite the availability of effective treatments. In many areas, the ability to diagnose HCV infection at the point of care is key to scaling up access to care and treatment. To achieve this, an accurate, easy-to-use and affordable diagnostic tool is required – this would enable decentralized testing and the creation of one-stop centers to eliminate

Congenital toxoplasmosis in humans and in some mammalian species, such as small ruminants, is a well-known cause of abortion and foetal malformations. The calcium-dependent protein kinase 1 (CDPK1) inhibitor BKI-1748 has shown a promising safety profile for its use in humans and a good efficacy against Toxoplasma gondii infection in vitro and in mouse models. The rates of congenital infection and foetal

BACKGROUND To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination

Most COVID-19 patients requiring ICU care develop an acute respiratory distress syndrome (ARDS), characterised by severe hypoxemia, decreased lung compliance, and high vascular permeability. Activation of the complement system is a hallmark of moderate and severe COVID-19, with abundant deposition of complement proteins reported in inflamed tissue and on the endothelium during COVID-19. Using a transgenic

Tuberculosis (TB) is the second leading infectious killer after COVID-19. Standard anti-tubercular drugs exhibit various limitations like toxicity, lengthy, and unresponsive to dormant and drug resistant organisms. Here, we report that all-trans-retinoic acid (ATRA) improves M.tb clearance in mice while treating with anti-tubercular drug isoniazid (INH). Interestingly, ATRA promoted activities of lysosomes

Background Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. Methods We reviewed electronic health records of patients who underwent testing for CD at four hospital systems

Background Universities returned to in-person learning in 2021 while SARS-CoV-2 spread remained high. At the time, it was not clear whether in-person learning would be a source of disease spread. Methods We combined surveillance testing, universal contact tracing, and viral genome sequencing to quantify introductions and identify likely on-campus spread. Results Ninety-one percent of viral genotypes

Periodontitis is an exemplar of dysbiosis associated with the coordinated action of multiple members within the microbial consortium. The Polymicrobial Synergy and Dysbiosis hypothesis proposes a dynamic host-microbiome balance, with certain modulators capable of disrupting eubiosis and driving shifts towards dysbiosis within community. However, these factors remain to be explored. We established a

Background It is unclear whether there are racial and/or ethnic disparities in the risk of acquiring an upper respiratory infection (URI) and/or the risk of lower respiratory manifestations of a URI. Methods We studied all children and children with asthma, 6-17 years of age in the National Health and Nutritional Examination Survey (2007-2012), to evaluate the association between race/ethnicity and

Orthopoxviruses are complex, large-genome DNA viruses that have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV) was originally characterized during outbreaks among captive primates in the late 1950's. Human disease (mpox) has been observed since the 1970’s and inter-human spread has largely been associated with non-sexual

Picornaviruses are nonenveloped particles with a single-stranded RNA genome of positive polarity. This virus family includes poliovirus, hepatitis A virus, rhinoviruses, and Coxsackieviruses. Picornaviruses are common human pathogens, and infection can result in a spectrum of serious illnesses, including acute flaccid myelitis, severe respiratory complications, and hand-foot-mouth disease. Despite

Research directed at select prototype pathogens is part of the approach put forth by the National Institute of Allergy and Infectious Disease (NIAID) to prepare for future pandemics caused by emerging viruses. We were tasked with identifying suitable prototypes for four virus families of the Bunyavirales order (Phenuiviridae, Peribunyaviridae, Nairoviridae, and Hantaviridae). This is a challenge due

The coronavirus disease 2019 (COVID-19) pandemic demonstrated how rapidly vaccines and monoclonal antibodies (mAbs) could be deployed when the field is prepared to respond to a novel virus, serving as proof of concept that the prototype pathogen approach is feasible. This success was built upon decades of foundational research, including the characterization of protective antigens and coronavirus immunity

Viruses in the family Filoviridae, including the commonly known Ebola (EBOV) and Marburg (MARV) viruses, can cause severe hemorrhagic fever in humans and nonhuman primates. Sporadic outbreaks of filovirus disease occur in sub-Saharan Africa with reported case fatality rates ranging from 25% to 90%. The high mortality and increasing frequency and magnitude of recent outbreaks along with the increased

Lassa virus (LASV), Junin virus (JUNV), and several other members of the Arenaviridae family are capable of zoonotic transfer to humans and induction of severe viral hemorrhagic fevers. Despite the importance of arenaviruses as potential pandemic pathogens, numerous gaps exist in scientific knowledge pertaining to this diverse family, including gaps in understanding replication, immunosuppression,

The Togaviridae family, genus, Alphavirus, includes several mosquito-borne human pathogens with the potential to spread to near pandemic proportions. Most of these are zoonotic, with spillover infections of humans and domestic animals, but a few such as chikungunya virus (CHIKV) have the ability to use humans as amplification hosts for transmission in urban settings and explosive outbreaks. Most alphaviruses

Flaviviruses are a genus within the Flaviviridae family of positive-strand RNA viruses and are transmitted principally through mosquito and tick vectors. These viruses are responsible for hundreds of millions of human infections worldwide per year that result in a range of illnesses from self-limiting febrile syndromes to severe neurotropic and viscerotropic diseases and, in some cases, death. A vaccine

Given the increased risk of pandemics driven by emerging and reemerging infectious diseases, it is imperative that the United States and global scientific community be better prepared for future threats by prioritizing and launching key research programs and strategies. In December 2021, the National Institute of Allergy and Infectious Diseases (NIAID) published its pandemic preparedness plan, which

The Paramyxoviridae family includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens such as Nipah virus; and a number of recently identified agents, such as Sosuga virus, which remain poorly understood. The high human-to-human transmission rate of paramyxoviruses such as measles virus, high case fatality rate associated

Cryptosporidium species are a major cause of diarrhea and associated with growth failure. There is currently only limited knowledge of the parasite's genomic variability. We report a genomic analysis of Cryptosporidium parvum isolated from Bangladeshi infants and reanalysis of sequences from the United Kingdom. Human isolates from both locations shared 154 variants not present in the cattle-derived

Abstsract Introduction In California, the 2022 mpox outbreak cumulated 5572 cases as of November 28, 2022, approximately 20% of the US case count; 0.3% of cases were among children <16 years old. The secondary attack rate for children sharing households with infected adults is unknown. Methods Using the California public health database, we created a line list of all pediatric mpox household contacts

INTRODUCTION With the licensure of maternal RSV vaccines in Europe and USA, data are needed to better characterize the burden of respiratory syncytial virus (RSV)-associated acute respiratory infections (ARI) in pregnancy. This study aims to determine among pregnant individuals the proportion of ARI testing positive for RSV and RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal

Background Exposures associated with mpox infection remain imperfectly understood. Methods We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox cases and test-negative controls. Results Thirteen