The burden of infectious diseases throughout and after the COVID-19 pandemic (2020-2023) and Russo-Ukrainian war migration.

Understanding how the infectious disease burden was affected throughout the COVID-19 pandemic is pivotal to identifying potential hot spots and guiding future mitigation measures. Therefore, our study aimed to analyze the changes in the rate of new cases of Poland's most frequent infectious diseases during the entire COVID-19 pandemic and after the influx of war refugees from Ukraine. We performed a registry-based population-wide study in Poland to analyze the changes in the rate of 24 infectious disease cases from 2020 to 2023 and compared them to the prepandemic period (2016-2019). Data were collected from publicly archived datasets of the Epimeld database published by national epidemiological authority institutions. The rate of most of the studied diseases (66.6%) revealed significantly negative correlations with the rate of SARS-CoV-2 infections. For the majority of infectious diseases, it substantially decreased in 2020 (in case of 83%) and 2021 (63%), following which it mostly rebounded to the prepandemic levels and, in some cases, exceeded them in 2023 when the exceptionally high annual rates of new cases of scarlet fever, Streptococcus pneumoniae infections, HIV infections, syphilis, gonococcal infections, and tick-borne encephalitis were noted. The rate of Clostridioides difficile enterocolitis was two-fold higher than before the pandemic from 2021 onward. The rate of Legionnaires' disease in 2023 also exceeded the prepandemic threshold, although this was due to a local outbreak unrelated to lifted COVID-19 pandemic restrictions or migration of war refugees. The influx of war migrants from Ukraine could impact the epidemiology of sexually transmitted diseases. The present analysis indicates that continued efforts are needed to prevent COVID-19 from overwhelming healthcare systems again and decreasing the control over the burden of other infectious diseases. It also identifies the potential tipping points that require additional mitigation measures, which are also discussed in the paper, to avoid escalation in the future.

Alert for pharynx-centered gastrointestinal and respiratory cross-infection and cryptic cross-transmission routes of 2019-nCoV.

We proposed that the pharynx, as a common organ of the respiratory and digestive tracts, may be a respiratory and digestive tract cross cryptic transmission pathway for 2019-nCoV infection from the nasal cavities to the pharynx and lung, then to nasal cavities by aerosol (respiratory route) to the pharynx and the gastrointestinal tract, then to the oral cavity by feces (fecal-oral route) and to pharynx, lungs, or gastrointestinal tract.

Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. DISCUSSION: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

Development of Ac2-26 Mesoporous Microparticle System as a Potential Therapeutic Agent for Inflammatory Bowel Diseases.

Introduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N-terminal mimetic peptides improve IBD symptomatology. Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N-terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut. Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26 into cultured Raw 264.7 macrophages and Caco-2 epithelial cells. Moreover, oral administration of Eudragit-SBA-15-Ac2-26 (200 µg; once a day; for 4 days) reduced colitis clinical symptoms, inflammation, and improved epithelium recovery in mice under dextran-sodium sulfate-induced colitis. Discussion: The absorption of SBA-15 in gut epithelial cells is typically low; however, the permeable inflamed barrier can enable microparticles to cross, being phagocyted by macrophages. These findings suggest that Ac2-26 is successfully delivered and binds to its receptors in both epithelial and immune cells, aligning with the clinical results. Conclusion: Our findings demonstrate a simple and cost-effective approach to delivering Ac2-26 orally into the inflamed gut, highlighting its potential as non-invasive IBD therapy.

Formulation Consideration of Medicated Chewing Gum: A Review.

In recent times, technological and scientific advances have been made in studying and developing orally delivered medication. Such studies demonstrate the importance of the oral route among patients. The accuracy of drug delivery is very important to achieve a successful therapeutic effect in the case of various pharmaceutical products. A novel drug delivery system adds new benefits or advantages to a drug. This review covers all the aspects of medicated chewing gum (MCG) as a new drug delivery method, including the benefits and drawbacks, manufacturing methods, type of MCG, composition of chewing gum, evaluation parameters, factors that affected the release of API, its pharmaceutical significance, various marketed chewing gum and chewing gum packaging. Chewing gum as a drug delivery system has the potential to cure or prevent various indications, such as analgesic, CNS stimulation, smoking cessation, motion sickness, and treatment and prevention of dental caries or gingivitis. Pharmaceutical distribution to the oral mucosa can be made more convenient and enticing with the help of MCG. Compared to conventional techniques, this delivery system has a longer-lasting effect, which makes it a viable option for treating digestive problems, headaches, migraines, coughing, anxiety, and allergies.

Natural lipid nanoparticles extracted from Morus nigra L. leaves for targeted treatment of hepatocellular carcinoma via the oral route.

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of 'medicine food homology', we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity index = 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.

Pharmaceutical Suspensions: An Updated Patent Review on Novel Suspending Agents and Recent Advancement.

A wide variety of dosage forms are used for the oral administration of drugs to humans and animals. Apart from solid dosage forms, it also includes liquid dosage forms, such as solutions, suspensions, and emulsions. The selection is based on the physiochemical attributes of the therapeutically active ingredient. Suspensions are classified as dispersed systems that are heterogeneous in nature and consist of two phases. One phase is the continuous phase, the dispersion medium, or the external phase, which is either liquid or semisolid; the other is a solid particle dispersed in the external phase and called an internal or dispersed phase. They have several advantages over other dosage forms, such as effectively delivering hydrophobic drugs, avoiding the need for cosolvents, masking unpleasant tastes, and providing resistance to degradation and easy swallowing for young or elderly patients. They also attain higher drug concentrations compared to solution forms. This review article aims to study and explore the advantages, novel suspending agents, patent preference, and innovations of pharmaceutical suspension. It was targeted to scrutinize the literature floating in the internet domain regarding pharmaceutical suspension for delivery of drugs by oral route. The literature survey is targeted at the novel herbal suspending agents used, their patents involved, and innovations in the dosage form. Further, the study gives an insight into various aspects of suspension, such as classification of suspension, theories of suspension, various components used in suspension formulation, formulation aspect of suspension, evaluation parameters of suspension, patents, innovations, and regulatory status.

SARS-CoV-2 sublingual vaccine with RBD antigen and poly(I:C) adjuvant: Preclinical study in cynomolgus macaques.

Mucosal vaccine for sublingual route was prepared with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and poly(I:C) adjuvant components. The efficacy of this sublingual vaccine was examined using Cynomolgus macaques. Nine of the macaque monkeys were divided into three groups of three animals: control [just 400 µg poly(I:C) per head], low dose [30 µg RBD and 400 µg poly(I:C) per head], and high dose [150 µg RBD and 400 µg poly(I:C) per head], respectively. N-acetylcysteine (NAC), a mild reducing agent losing mucin barrier, was used to enhance vaccine delivery to mucosal immune cells. RBD-specific IgA antibody secreted in pituita was detected in two of three monkeys of the high dose group and one of three animals of the low dose group. RBD-specific IgG and/or IgA antibodies in plasma were also detected in these monkeys. These indicated that the sublingual vaccine stimulated mucosal immune response to produce antigen-specific secretory IgA antibodies in pituita and/or saliva. This sublingual vaccine also affected systemic immune response to produce IgG (IgA) in plasma. Little RBD-specific IgE was detected in plasma, suggesting no allergic antigenicity of this sublingual vaccine. Thus, SARS-CoV-2 sublingual vaccine consisting of poly(I:C) adjuvant showed reasonable efficacy in a non-human primate model.

Milk Transmission of Mammalian Retroviruses.

The transmission of viruses from one host to another typically occurs through horizontal or vertical pathways. The horizontal pathways include transmission amongst individuals, usually through bodily fluids or excretions, while vertical transmission transpires from mother to their offspring, either during pregnancy, childbirth, or breastfeeding. While there are more than 200 human pathogenic viruses to date, only a small number of them are known to be transmitted via breast milk, including cytomegalovirus (CMV), human immunodeficiency virus type 1 (HIV-1), and human T cell lymphotropic virus type 1 (HTLV-1), the latter two belonging to the family Retroviridae. Breast milk transmission is a common characteristic among mammalian retroviruses, but there is a lack of reports summarizing our knowledge regarding this route of transmission of mammalian retroviruses. Here, we provide an overview of the transmission of mammalian exogenous retroviruses with a focus on Orthoretrovirinae, and we highlight whether they have been described or suspected to be transmitted through breast milk, covering various species. We also elaborate on the production and composition of breast milk and discuss potential entry sites of exogenous mammalian retroviruses during oral transmission.

A Perspective on Oral Immunotherapeutic Tools and Strategies for Autoimmune Disorders.

Oral immune tolerance is a physiological process to achieve tolerance against autoimmunity by oral ingestion of self-antigen(s) or other therapeutics. At the cellular level, oral tolerance suppresses autoimmune diseases by activating FoxP-positive and -negative regulatory T cells (Tregs) and/or causing clonal anergy or deletion of autoreactive T cells, affecting B cell tolerance. However, oral delivery of antigens/biologics is challenging due to their instability in the harsh environment of the gastrointestinal (GI) tract. Several antigen/drug delivery tools and approaches, including micro/nanoparticles and transgenic plant-based delivery systems, have been explored to demonstrate oral immune tolerance for different autoimmune diseases successfully. However, despite the effectiveness, variation in results, dose optimization, and undesirable immune system activation are the limitations of the oral approach to further advancement. From this perspective, the current review discusses the oral tolerance phenomenon, cellular mechanisms, antigen delivery tools and strategies, and its challenges.

Data on ADME parameters of bisphenol A and its metabolites for use in physiologically based pharmacokinetic modelling.

The paper presents the collection of physicochemical parameters of bisphenol A (BPA) and its sulfate (BPAS) and glucuronide (BPAG) conjugates, accompanied by data characterizing their absorption, distribution, metabolism and excretion (ADME) behavior following oral administration of BPA. The data were collected from open literature sources and publicly available databases. Additionally, data calculated by using the MarvinSketch 18.30.0 software or predicted by relevant QSAR models built in Simcyp® Simulator were also used. All data were analysed and are fit for purpose if necessary to ensure a reliable prediction of pharmacokinetics of BPA and its conjugates. The data selection process and reasoning for fitting is provided to allow critical assessment and to ensure data transparency. Finally, the sensitivity analysis was performed to assess the influence of the selected parameters on the PBPK model predictions.

Transmission routes and patterns of helicobacter pylori.

BACKGROUND AND OBJECTIVE: Helicobacter pylori (H. pylori), a gram-negative bacterium that colonizes the stomach, can cause chronic gastritis and peptic ulcers, as well as gastric cancer as a Class I carcinogen. However, the modes of H. pylori transmission are not clear. This review aims to clarify the transmission routes and patterns of H. pylori and identify efficacious prevention measures. METHODS: Studies of H. pylori transmission were identified using PubMed, the Web of Science, and Cochrane Central; the retrieval deadline was October 2022. RESULTS: The transmission routes of H. pylori are discussed, focusing on the five primary transmission routes, namely fecal-oral, oral-oral, gastric-oral, anal-oral, and genital-oral. We propose that H. pylori is contracted through multiple transmission routes. Additionally, we summarize the key transmission patterns of H. pylori, including person-to-person and animal-to-human transmission, as well as foodborne and occupational exposure. CONCLUSION: Fecal-oral appears to be the most common H. pylori transmission routes. Although the oral-oral pathway is also important, the evidence does not support that this route of transmission is universal. The gastric-oral route occurs primarily in children and patients who are prone to vomiting. Meanwhile, the anal-oral and genital-oral routes remain hypothetical. Person-to-person and foodborne infections represent the predominant transmission patterns of H. pylori, whereas strong environmental and occupational limitations are associated with animal-to-human and occupational exposure.

Development of a Nanoformulation for Oral Protein Administration: Characterization and Preclinical Orofacial Antinociceptive Effect.

Nanoencapsulation is a valid alternative for the oral administration of peptide drugs and proteins, as nanoparticles protect them from proteolytic degradation in the gastrointestinal tract and promote the absorption of these macromolecules. The orofacial antinociceptive effect of frutalin (FTL), through the intraperitoneal route, has already been proven. This study aimed to develop, characterize, and evaluate the orofacial antinociceptive activity of an oral formulation containing FTL in acute and neuropathic preclinical tests. Nanoencapsulated FTL was administered by oral route. The acute nociceptive behavior was induced by administering capsaicin to the upper lip and NaCl to the right cornea. The nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The neuropathic pain model involved infraorbital nerve transection (IONX), which induced mechanical hypersensitivity and was assessed by von Frey stimulation. Trpv1 gene expression was analyzed in the trigeminal ganglion. The analyzed sample did not show any cytotoxicity; 52.2% of the FTL was encapsulated, and the size of the nanocapsule was less than 200 nm, the polydispersion was 0.361, and the zeta potential was - 5.87 and - 12.8 mV, with and without FTL, respectively. Nanoencapsulated FTL administered by oral route had an orofacial antinociceptive effect in acute and neuropathic rodent models. The antinociceptive effect of FTL was prevented by ruthenium red, but not by camphor. FTL reduced Trpv1 gene expression. FTL promotes orofacial antinociception, probably due to the antagonism of TRPV1 channels, and the nanoformulation represents an effective method for the oral administration of this protein. HIGHLIGHTS: • Nanoformulation for oral protein administration. • Nanocapsule containing FTL prevents orofacial nociceptive acute and neuropathic pain. • Frutalin promotes orofacial antinociception behavior antagonism of TRPV1 channels.

Estimation of multi-route exposures to various chemicals during Children's clay toy use.

Clay toys have been used as play materials and educational tools for children. Clay toys exhibit adherent properties, and may facilitate chemical ingestion via dermal absorption and oral (hand-to-mouth, HTM) exposures. Inhalation exposure also be considered when contain volatile chemicals. The purpose of this study was to estimate the exposure dose for chemicals in clay toys via three exposure routes, and to evaluate the relationship between the exposure contribution of each route considering both the chemical properties and children's age. Chemical analysis was conducted for 9 semi-volatile organic compounds (SVOCs), 17 volatile organic compounds (VOCs), and 7 metal elements in clay toys (n = 66) purchased from Korean market. Exposure factors for usage pattern of clay toys were conducted based on a nationally representative survey in Korea. A total of 12,144 (60.7%) children responded positively to playing with clay toys. Exposure to SVOCs and VOCs in clay toys via HTM, inhalation, and dermal absorption were estimated. The exposure level was the highest in styrene with 5.2 × 10-3 mg/kg-bw/day (95th percentile population), which was approximately 13% of the acceptable daily dose for styrene. In 3-year-old children, dermal absorption route contributed the highest at 59.2-100%. Chemicals with higher octanol-water partition coefficient (Kow) had the greater the contribution of the dermal absorption route and the weaker the contribution of the HTM route. In infants (0-2 years), the contribution via HTM exposure was higher than that in the other age groups. The contribution of inhalation exposure differed depending on the volatility of the chemicals. Furthermore, the exposure route contribution significantly differed due to age-dependent behavioral changes in children. These results suggest that the exposure assessments for children could be considered with multiple exposure routes related to chemical properties.

Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes.

Liposomal amphotericin B (AmB) or AmBisome® is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome® in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome® in Leishmania amazonensis-infected BALB/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100-130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes.

Milk Transmission of HTLV-1 and the Need for Innovative Prevention Strategies.

Breastfeeding is recommended by the World Health Organization for at least 6 months up to 2 years of age, and breast milk protects against several diseases and infections. Intriguingly, few viruses are transmitted via breastfeeding including Human T-cell leukemia virus Type 1 (HTLV-1). HTLV-1 is a highly oncogenic yet neglected retrovirus, which primarily infects CD4+ T-cells in vivo and causes incurable diseases like HTLV-1-associated inflammatory conditions or Adult T-cell leukemia/lymphoma (ATLL) after lifelong viral persistence. Worldwide, at least 5-10 million people are HTLV-1-infected and most of them are unaware of their infection posing the risk of silent transmissions. HTLV-1 is transmitted via cell-containing body fluids such as blood products, semen, and breast milk, which constitutes the major route of mother-to-child transmission (MTCT). Risk of transmission increases with the duration of breastfeeding, however, abstinence from breastfeeding as it is recommended in some endemic countries is not an option in resource-limited settings or underrepresented areas and populations. Despite significant progress in understanding details of HTLV-1 cell-to-cell transmission, it is still not fully understood, which cells in which organs get infected via the oral route, how these cells get infected, how breast milk affects this route of infection and how to inhibit oral transmission despite breastfeeding, which is an urgent need especially in underrepresented areas of the world. Here, we review these questions and provide an outlook how future research could help to uncover prevention strategies that might ultimately allow infants to benefit from breastfeeding while reducing the risk of HTLV-1 transmission.

Comparative analysis of groundwater quality statuses and associated health risk indices of metals and total hydrocarbons at locations of tank farm in Delta State, Nigeria.

The study aimed at assessing the groundwater quality and the associated health implications of oil storage tank farms in Asaba, Oghara, Warri, and Koko towns, in Delta State, Nigeria. Fe, Cr, Cd, Ni, Pb, and V concentrations in the groundwater samples were determined using Atomic Absorption Spectrophotometry (AAS), while total hydrocarbons (THC) concentrations were determined using gas chromatography coupled with a flame ionization detector (GC-FID). The quality index of Warri groundwater was 66.38; being within the range of 51-75 was considered poor quality. The water quality indices (WQI) of Oghara, Koko, and Asaba were 163.79, 161.43, and 129.95 respectively, which were all > 100, hence amounting to very poor water quality status. Results indicated that children in Oghara who are orally exposed to chromium are at risk of cancer. Both adults and children orally exposed to THC in Oghara are also at risk of cancer. Furthermore, THC posed an oral route cancer risk to the children in Koko town. The study showed that chromium posed carcinogenic threats to children in Oghara, while THC posed carcinogenic threats to adults and children in Oghara and children alone in Koko. These risks are liable to be mediated through ingestion of the groundwater of Oghara and Koko by the susceptible groups.

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations.

The liposomal amphotericin B (AmB) formulation, AmBisome®, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, its clinical efficacy depends on the patient's immunological status, the clinical manifestation and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. This review reports the progress achieved thus far toward the understanding of the mechanism responsible for the reduced toxicity of liposomal AmB formulations and the factors that influence their efficacy against leishmaniasis. It also presents the recent advances in the development of more effective liposomal AmB formulations, including topical and oral liposome formulations. The critical role of the AmB aggregation state and release rate in the reduction of drug toxicity and in the drug efficacy by non-invasive routes is emphasized. This paper is expected to guide future research and development of innovative liposomal formulations of AmB.

Using QMRA to understand possible exposure risks of SARS-CoV-2 from the water environment.

This study investigated the human risk of infection due to inadvertent ingestion of water during swimming in a river that receives SARS-CoV-2-containing effluent from a wastewater treatment plant (WWTP). A quantitative microbial risk assessment (QMRA) approach was applied for risk estimation using dose-response models (DRM) of different surrogate coronaviruses (SARS-CoV-1, MERS-CoV) and the virus responsible for most infectious respiratory illnesses (i.e., influenza A H5N1) due to the unavailability of DRM for SARS-CoV-2. The ratio of infectious concentration to genomic copies of SARS-CoV-2 is unknown and also unavailable for other coronaviruses. Therefore, literature-based information on enteric viruses was used for formulating the ratio used for QMRA, although it is acknowledged that identifying this information for SARS-CoV-2 is a priority, and in the absence of information specific to SARS-CoV-2, another coronavirus would be a preferable surrogate to the enteric viruses used here. The calculated concentration of ingested SARS-CoV-2 ranged between 4.6 × 10-7 and 80.5 genomic copies/dip (one swim = 32 mL). The risk of infection (> 9 × 10-12 to 5.8 × 10-1) was found to be > 1/10,000 annual risk of infection. Moreover, the study revealed that the risk estimation was largely dependent on the value of the molecular concentration of SARS-CoV-2 (gc/mL). Overall immediate attention is required for obtaining information on the (i) ratio of infectious virus to genomic copies, (ii) DRM for SARS-CoV-2, and (iii) virus reduction rate after treatment in the WWTPs. The QMRA structure used in present findings is helpful in analyzing and prioritizing upcoming health risks due to swimming performed in contaminated rivers during the COVID-19 outbreak.

In vivo imaging of retrovirus infection reveals a role for Siglec-1/CD169 in multiple routes of transmission.

Early events in retrovirus transmission are determined by interactions between incoming viruses and frontline cells near entry sites. Despite their importance for retroviral pathogenesis, very little is known about these events. We developed a bioluminescence imaging (BLI)-guided multiscale imaging approach to study these events in vivo. Engineered murine leukemia reporter viruses allowed us to monitor individual stages of retrovirus life cycle including virus particle flow, virus entry into cells, infection and spread for retroorbital, subcutaneous, and oral routes. BLI permitted temporal tracking of orally administered retroviruses along the gastrointestinal tract as they traversed the lumen through Peyer's patches to reach the draining mesenteric sac. Importantly, capture and acquisition of lymph-, blood-, and milk-borne retroviruses spanning three routes was promoted by a common host factor, the I-type lectin CD169, expressed on sentinel macrophages. These results highlight how retroviruses co-opt the immune surveillance function of tissue-resident sentinel macrophages for establishing infection.