Betacoronaviridae) and other viral pathogen mechanisms of transmission are expected. Unfortunately, unprecedented, and growing distrust of vaccines and even masks or personal protective equipment (PPE) in the United States and elsewhere presents itself as an added challenge. We postulate that development of improved and highly effective prophylactic measures, together with new life-saving therapies that do inhibit or otherwise treat infection of SARS-CoV-2, influenza and other viral pathogens, could be an adjunct measure to globally protect vulnerable individuals from pandemic threats. In this review, we share what we learned from the past COVID experience to offer a multifactorial and improved approach to current and future pandemic infections or threats using low-cost means.Since influenza and coronaviruses are currently deadly and emerging threats worldwide, better treatment, remediation and prevention options are needed. In that regard, a basic understanding of severe acute respiratory syndrome (SARS)-CoV-2/COVID-19 ( Engineering approaches, including those for improved personal protective equipment (PPE) and remediation of fomite transfer has been one focus for dealing with the recent SARS-CoV-2 virus pandemic and its community spread. Once it emerged in 2019 in Wuhan City, Hubei Province, China, the COVID pandemic has become endemic in most of the world. Early in the pandemic, SARS-CoV-2 rapidly spread throughout the world and, as pandemics trend to do, has infected all continents in just a matter of months. The pandemic has wrought financial havoc and taken a significant, but not unprecedented human toll. Yet, this virus demonstrates extreme resilience; it was highly mutated and transmissible. One might say the virulence of this pandemic was overall mild and the world was lucky that it was not more virulent. However, luck is a poor strategy going forward and, in this paper, we lay out our approach to past and future respiratory pandemic prophylaxis.The specter of another pandemic looms large, since we know there are numerous new variants to older strains and new emerging pathogens. A recent strain of H1N1, swine flu (G4 EA H1N1), has recently emerged in China and may continue to spread throughout China or elsewhere. This new virus strain and other SARS variants have all the essential hallmarks of another candidate pandemic virus .Unfortunately, these approaches are not fully accepted, and can be costly or take months to years to develop. Therefore, the world population requires more rapid and universal protective approaches, and that next logical step would be to design, and wear improved or enhanced PPE (EPPE). Moreover, employing highly effective virus-trapping and eradicating measures including: (i) engineering better air handling and filtration, (ii) improving PPE and (iii) general virucidal approaches are the first line and least expensive means to managing future pandemics world-wide. In this review, we propose concepts and share the concepts that we formulated to remediate the threat at that very precarious time in our collective histories. We are sharing the technology while retaining all rights and intellectual property this disclosure should entails in the effort to share what we learned.To be clear, elimination of fomites, which involves basic physical removal of pathogens, is accomplished through surface disinfectant application or handwashing coupled with engineering controls, like UV-C germicidal light and air filtration . The focWe have devised an additional approach to test mask design, its coating effectiveness or to predict either adhesion or repulsion. In that regard, an accurate Iso-electric point (IEP) is key to understanding that process to address a more global and functionally simple approach to personal protection equipment (PPE). For IEP measurements, we designed the chemical force microscopy (CFM) method to experimentally measure the IEP in relevant physiological conditions and as a single particle (27). This method reduces the necessity for highly purified samples, which is required for many IEP measurements.To accomplish testing, we first devised a material testing chamber see , where oNext, we devised a complete wearable electronic devices or headgear setup for the repulsion of viral particles using electronic conductive mesh made of parallel wires properly spaced to effectively conduct current unidirectionally. The power sources were are supplied from a mobile phone or a compact power bank via a standard mini universal serial bus to provide constant power for a tunable electric field with various strength at given input applied voltages.SARsCoV2 Virus isolates Working with non-BSL methods and the testing chamber, we obtained heat-inactivated and gamma-irradiated isolates from BEI Resources  for SARS-CoV-2 (USA-WA1/2020).The routes of transmission for SARSCoV2 (coronaviridiae) and other respiratory diseases, largely involve inhalation of small airborne “respiratory droplets”, which can be large over 100 microns) or small (less than 100 microns) in size. The result has been deadly, and the consequences of the pandemic continue to this day and is now an endemic corona virus. Infection occurs through direct contact with infected people and to a lesser extent by contact with contaminated surfaces. COVID-19 is a respiratory virus and the significance of viral transmission via small airborne microdroplets, also known as aerosols, has been extensively reviewed. We briefly discuss transmission in the context of SARS coronavirus-2 pandemic as background to the presenting problem . Uncerta0 micronsIt has been said that sunlight is the best disinfectant. This is based on the sanitizing power of light in the ultraviolet (UV) electromagnetic spectrum, which is germicidal and virucidal. Ultraviolet germicidal irradiation (UVGI), particularly UV-C in the range of 253–260 nm, may offer added disinfection benefits. In contrast, to many disinfectant products, applied UVGI is an effective eradication method for the inactivation of microorganisms, including viruses  on surfaUnder laboratory conditions, UVGI has been shown to be effective against a suite of microorganisms including coronaviruses , vaccini2 for ssRNA, 2.50 to 4.47 mJ/cm2 for ssDNA, 3.80 to 5.36 mJ/cm2 for dsRNA, and 7.70 to 8.13 mJ/cm2 for dsDNA. They further measured the dose for all four tested viruses at 99% reduction levels were 2-fold higher than those required for a 90% viral reduction and found UV doses at 85% relative humidity were more effective than at 55% relative humidity, which suggests the hotter warmer summer months and warmers climate could offer some differential season relief during some outbreaks. UVC can generate reactive oxygen species (ROS), together with reactive nitrogen species (RNS) and reactive sulfur species (RSS) are free radicals, which are known to play a role in biological systems and can be either harmful or beneficial to the living organisms. ROS and RNS at low concentrations are well-known defense against infectious agents and viruses.Mechanisms of UVGI disinfection for microorganisms are effective due to protein lipid and nucleic acid modification, crosslinking, and damage to vulnerable residues at the level of their primary structure because the maximum absorption wavelength of DNA and RNA molecules is around 260–280 nm. Studies have evaluated UVGI effectiveness in terms of dose and on viral nucleic acid type, namely single-stranded RNA (ssRNA), double-stranded RNA (dsRNA), single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) . VirusesThe physical and chemical properties of the virus, when paired with specific environmental conditions can facilitate virus adsorption to fomites and dictate the time viral particles stay infectious in aerosols and droplets. Thus, the surface characteristics of a virus are important. To characterize the structural properties, we explore protein folding, hydrophobicity and surface charge. One important surface characteristic of a virus particle is the virus surface charge, which is characterized by the isoelectric point. The viral IEP corresponds to the pH where the net charge on the virus particle is zero. Since the viruses in question are contained in human oral and respiratory secretions, the pH for binding aerosolized droplets must be 4.5–6, which is close to the IEP for SARS-CoV-2. The physical and chemical properties of the virus paired with environmental conditions facilitate virus adsorption . The adhFor now, only experimental measurements are proving accurate for IEP elucidation, as our findings suggest for enveloped viruses like SARS-CoV-2. Estimates of IEP by the amino acid sequence or sequence homology algorithms alone may be unreliable. The IEP values were obtained based on the identified proteins on SARS-CoV-2. When we compared the experimental IEP of SARS-CoV-2 to variants of interest using amino acid sequences and provided a qualitative comparison of the IEP of variants. BLAST and FASTA scans are typical search tools, which are performed on a nucleotide or amino acid sequence to impart structural information or predict function of homologous proteins. The FASTA sequence was inputted into the Protparam tool from the Bioinformatics Resource Portal ExPASy to give us the putative structural information. Conventional methods for virus IEP measurements use bulk viral solutions. Zeta potential measures the electrostatic potential difference between the electric double layer surrounding the virus particle and the surrounding solution at the shear plane as we described. Another IEP measurement is isoelectric-focusing and capillary isoelectric-focusing, which both require the fluorescently tagged viruses and pure, concentrated solutions. We developed a single-particle method to measure the IEP of virus with an atomic force microscope (AFM). The technique is called chemical force microscopy (CFM), which uses a functionalized AFM tip to measure the adhesion force of the tip and the virus immobilized on a surface. When working with our non-BSL methods and testing chamber, we utilized BEI resources for SARS-CoV-2heat-inactivated and gamma-irradiated isolates. We were found to uniquely differ, as expected. The heat-inactivated virus contained many small particles and was not further tested; it was 5.2–5.3. This is on the low end of the IEPs from the calculated sources .The macromolecular structure of virus is highly dependent on the type of virus, non-enveloped or enveloped. Non-enveloped viruses have a protein capsid on their surface. One of the simplest examples is porcine parvovirus (PPV). It has 60 copies of a surface protein, with 80% being VP2 . HoweverWhile we can determine the exact amino acids and their glycosylation that are surface exposed, IEP is still not accurate for large biomolecules. Taking advantage of viral IEP can be one approach to repelling or attracting live virus. While evidence exists that this approach could work, little is known about the most virulent viruses and approaches to modifying masks using applied non-specific electrostatic forces could have unforeseen consequences, namely, unintended exposure. Understanding virus adsorption can help to facilitate safe practices and aid in improving PPE. For example, learning how to repel viruses from surfaces or to adsorb them could be used to improve filtration devices and build better PPE. The physicochemical properties of the virus paired with environmental conditions facilitate virus adsorption . FurtherThere are often large, charged patches distributed on the viral surface at the IEP. Once an accurate IEP is determined, it is likely that the distribution of charge on the surface of the virus may play a critical role in electrostatic adhesion. Work studying the adhesion of proteins to ionic chromatography resins has shown that proteins can have different charge, yet the same adhesion strength . So, disMany and wide-ranging viral isoelectric points have been characterized. These interaction properties are established under specific pH conditions, which can be difficult to ascertain or know fully with modeling. The surface charge can be used to design virus removal filters based on electrostatic adsorption ,37. One In that regard, molecular diagnostic methods were employed in unprecedented speed to first identify the novel coronavirus that was causing COVID19. By January 2020, we had the first viral sequence  and by MOne goal, which we base this report upon, was to offer PPE containing a decoy and inhibit or kill viruses by such means as cognate substrates and drugs or inhibitors. The aim was to find means to specifically bind target proteins for example to Hemagglutinin (HA) and Neuraminidases (NA) for Influenza, and the S-protein for COVID, effectively locking these viral pathogens it in a configuration through hydrogen bonding or covalent interaction that prevents fusion to cellular membranes through the receptor binding domain (RBD) of target viruses. In effect, this is a trap and a cellular decoy that would improve PPE, which is currently inadequate to protect the wearer fully. After exploring host binding by viral particles, which all work on step one through similar mechanisms by receptor binding to the cell surface on host cells and many chemical compounds, it was apparent that targeting the chemical components the virus utilizes for receptor binding and transmission would prevent infection of cells and tissues and constitute an effective prophylactic approach to emerging pandemics world-wide. In this way, we defeat and inactivate the viruses before any opportunity to infect their hosts and holding the virions in a stable configuration would help prevent bystander or self-inoculation. This work targets among such targets as ACE2 receptor and hemagglutinin through sialic acids, which are components of carbohydrate chains. In particularly, n-acetyl neuraminic acid is a glycoconjugate involved in cell–cell and cell-pathogen interactions and the main target that would be used to compete for host-pathogen interaction. The expressions of SAs are highly conserved from echinoderms to humans, where they constitute components of cell surface glycoproteins and gangliosides. They largely occupy terminal positions as individual monosaccharides or as oligosaccharides or polymers but infrequently. They are found in secreted glycoconjugates and in oligosaccharides, in blood, serum, milk or in mucus or other secretions .In addition to using charge attraction and repulsion, we also considered more specific biochemical compounds, such as N-acetyl Neuraminic acid (Neu5Ac), SAs and other cognate biomimetic cellular components that viruses use to invade host cells and tissues. Hemagglutinin and Neuraminidases are involved in H1N1 influenza, and others, along with COVID-19 and SARS which use surface S-Proteins or spikes. All have a critical role in viral infection. Cell surface glycoproteins that contain a terminal SA or Neu5Ac are some of the targets of several viruses of concern. These are innocuous host cellular carbohydrate adducts on proteins that viruses exploit to enter cells and tissues. As positive controls, we will use actual lysed cellular membranes and specific drugs targeting the viral neuraminidases and ACE2. These same components will serve as human tissue and cellular mimetics when used on masks and filters. Here, they will attract, capture and otherwise inactivate viral particles, such as coronaviruses, SARS or any novel pathogen we choose. In this way, infectivity and virulence could be attenuated for deadly pathogenic species without the host being infected. For a general cytotoxic filtration fiber coating, sulfonic acid polymers and other natural coatings will be utilized, which will trap and likely kill bacteria and viruses that come in-contact with the fibers.The application of virucidal substrates together with repulsive electric fields is what we refer to as a protective shield approach to airborne viral pathogens see ; they arMetal oxides like titanium, zinc and iron oxides and copper nanoparticles are often used in nanoparticle work . The antCost becomes an issue with silver and gold metals and impregnated material. A more economical approach is to use silver/copper alloy nanoparticles. The antiviral properties of a silver/copper alloy nanoparticle-coated masks or High Efficiency Particulate Air (HEPA) filter was evaluated in air filtration systems of aircrafts and commercial buildings. The ability of nanoparticles  when deposited on HEPA filters to stop and neutralize coronaviruseswere investigated ,48. ExisSamples of a HEPA filter will be coated with metal nanoparticles using the low-cost copper alloys nanoparticles and their performance is compared to the more expensive silver and gold nanoparticles. Nanoparticles are synthesized via an atmospheric spark discharge method and deposited onto commercially available filters using forced convection flow . A contrWhen considering attraction versus repulsion there could be bystander consequences or unintended static forces, e.g., contamination as well as intended forces, which we call pinning. Because the electric charge accumulation of the RNA viruses is much less than the electrostatic charges accumulated in the layers of the mask within a few minutes, this would minimize the bystander effect. However, if one adds a virucidal substrate or coating the bystander effect is minimized or perhaps eliminated. If dust floats near an object at high voltage, or becomes highly charged, the dust will usually be attracted and then will often stick to the object. The behavior may seem counterintuitive as opposite charges attract, same charges repel, an uncharged dust particle should be unaffected by a charged object . HoweverContact electrification could be considered using a set of layers to create and hold charges from electrostatic interactions, also known as triboelectric charging. Here, a type of electrical charging is generated with materials, such as cotton to polyester or nylon. These layer examples become charged, usually with separation or movement of material with which they are in contact. In this regard, layers can create and hold charges. The layers could consist of the inner surface of cotton or type of non-conducting material, which is basically a moisture wick and a nonconductor so that the electrostatic charges produced inside the layers do not drain out through the surface of the face. Most electrostatic applied charges are positive, and it is suggested that virus is bound by this. Since the charges could attract virus particles, a bystander effect could be contraindicated as a main approach .Since the COVID-19 comprises an amount of micro-sized droplet nuclei carrying a net electric charge, a supplemental conductive mesh layer is used to a contact DC current for a wearable voltage generator to supply negative charge to the conductive mesh . The conCOMSOL simulation is used to estimate the electric field distribution by varying different parameters: electric field strengths, electric field directions, and in extreme cases safe electric fields and breakdown field strengths. The electrons/ions continuity equations in two- and three-dimensional models are setup using a point to plane configuration. At the interfaces, the divergence condition implies a condition on the normal component of the field and the curl condition implies a condition on the tangential component of the field . The mas4 nucleotide substitutions per year [Viruses like SARS and H1N1 can survive on fomites from 4 h up to 24 h  and can per year  suggestsper year .Masks and respirators are arguably the most important piece of PPE. In this section, we outline the general mask design construct. The three-layer mask design see  can be mN-acetylated (GlcNAc)/N-sulfated glucosamine (GlcNS) and glucuronic acid (GlcA) are a able to capture viral spike proteins [Coatings are diverse but center around a few key concepts, namely binding or trapping agents to fix and secure virions and virucidal substrate to kill any incident particle or pathogen. For example, HA or the S-protein interact and locks in a configuration on a non-cellular surface that would prevent fusion of the cellular and viral membranes in vitro. In effect this is a trap and a cellular decoy. Below is an example list of targets to achieve this goal by type and include N-Acetylneuraminic acid (Neu5Ac), NA inhibitors like Oseltamivir, O-GlucNAcase inhibitors like Thiamet G and sugar analogues like disaccharide or polysaccharide decoys bound on a matrix scaffold to mask material. Utilizing viral binding moieties to trap coronavirus, we turned to sugars, glycans carbohydrate polymers and matrigels, which are the first innocuous and effective coating to consider, and evidence suggests proteins . FurtherGelidium sp. and Gracilaria; genera of carrageenan-containing red seaweed Chondrus crispus, Gigartina, Iridaea, Kappaphycus alvarezii and Euchema denticulatum are used most widely [Cladophora spp. of green algae is used for purpose of hydrocolloid production and some species of seaweed may contain native toxic compounds [Seaweed utilization as raw material for the production of hydro- colloids—agar, carrageenan from red seaweed and alginates from brown seaweed, which are used in food and cosmetics industry and also in medicine and pharmaceuticals. It is the features of biologically important N-glycans, N-glycopeptides N-glycans linked to glycoproteins found in various seaweed species that have been identified, characterized and of which we take note . Diverset widely . Only hit widely . Except ompounds .Support for NA and GA use comes from development of inhibitors of enzymatic cleavage of host sugars, which have been in trial and are effective at preventing infections for some viral species, but not all. Interestingly, these approaches also include targets of sialic acid residues. Neuraminic acid inhibitors are based on enzymatic hydrolysis of the sialic acid (Neu5Ac)-terminated glycoprotein. Two possible strategies have been applied through devising congeners or the related compounds having comparable chemical structures and biological functions, and the conjugate, which are compounds involving two bioactive substrates joined through covalent bonding  Small moNatural compounds to inhibit, inactivate and kill COVID-19 are likely future considerations, as is evaluating tissue mimetics and agents known to block, trap, inhibit or inactivate aerosolized viruses, before they infect their host, would be a technological leap forward for PPE and disease management. To delineate mechanisms, predict interruptions to common infection features and suggest improved personalized treatment is the expected outcome. Moreover, adding virucidal coating could further enhance the trapping and offer safe means of eradication with such substrates as sulfones and thiocyanate or peroxide-based disinfectants or virucides. At physiological pH, hypothiocyanite (produced in this system) is believed to mediate the oxidation of essential bacterial amino acids and the SH group of the enzyme to suppress bacterial activity. There is also a theory that lactoperoxidase is involved in the formation of higher oxyacids of thiocyanate ions such as cyanosulfite and cyanosulfate, which are also thought to have antibacterial effects that suppress bacterial activity . The impUnfortunately, the antibacterial or antiviral mechanism of the thiocyanate/peroxidase/hydrogen peroxide system has not yet been accurately confirmed. We proposed the use of toluene sulfonic acid polymers such as those used currently in preparation of ion exchange residues and unprotonated p-toluene-sulfonic (TpOH) acid matrigels as another less safe but highly effective approach to the hydrophobic outermost layers of a multi-part mask. The key to this approach is to use the column chromatography chemistry to fix, bind or otherwise adhere the sorbent substrate to the outer parts of the PPE to immobilize it and make it permanently stable. The toluene substituents withdrawing electron density from the aromatic ring. An example of this is the nitration of toluene during the production of trinitrotoluene. Toluene is used extensively as a solvent in the lacquer industry, and in the explosives industry it plays an important role as a starting material for trinitrotoluene . ImportaThe electrostatic binding potential of several promising natural substrates, such as small phenolic molecules (≤2000 Da), Safer coatings are key to public acceptance and many of the natural products and COVID-19 drugs that inhibit viral docking and entry are now known to be almost exclusively small phenolic and polyphenolic compounds. Applying these compounds to our novel assay system (see testing chamber), we expect small phenolic molecules will act as a decoy or otherwise bind and trap many viruses. Most of these small phenolic molecules are bioactive. This provides a potential mechanism through which chemicals, such as sialic acid or sulfonic acid, fixed to select proteoglycans, Matrigel and alginates could also inactivate or kill viruses. We propose to survey, test and evaluate these small phenolic molecules in relation to their trapping or inhibiting properties. Small phenolic molecules have been previously associated with antiviral and inhibiting activity. However, attempts to define their clinical implications were hampered by experimental constraints and sometimes toxicity. The available data on use of phenolic acids with COVID19 is largely unexplored and mechanistic explanations are often lacking. Advances in structural elucidation the RBD of many viruses and a reconceptualization of PPE demand a reevaluation of these small phenolic molecules and matrices.There are in addition, multiple other potential matrices, mostly natural products, which studies have shown mediate inhibition of viruses. The fact that Glycosaminoglycans (GAGs) in particular. heparan sulfate (HS), and heparin (Hp), which are the most highly charged macromolecules in animals suggests that electrostatic forces play significant roles in modulating their protein affinity. Such long-range interactions are typically relegated to supportive roles in protein recognition and one reason specificity and hydrogen binding becomes key in trapping and immobilizing the viruses in place. Key charged proteoglycans, seaweed and heparan sulfate are associated with inhibition of COVID-19 and other virus. In preliminary exploration, several types of proteoglycans and sulfated matrices have been shown to inhibit COVID-19 in vitro. However, multiple possible confounds remain to be adequately resolved. Accordingly, we also will conduct a combinatorial exploration of a wide range of small molecules in hydrogel coated melt blow fibers.The presenting problem in early 2020, now known as the days of COVID-19, was how does one address emerging viral threats ahead of any available vaccines, without engaging rolling draconian lockdowns. Furthermore, complications arose when science was targeted by disinformation campaigns. This resulted in a significant change in attitude towards wearing masking and taking vaccines. Virology and public health requests and mandates were largely ignored, and science was found out of favor by some citizens s refuse to respect science or comply with physical restrictions. Efforts to change behavior about PPE failed and in these select countries, the behavior put at risk individuals with advanced age or compromised health. Moreover, when these approaches fail, as they did, perhaps having a superior product with improved function could have changed the outcomes and saved countless lives. One then, logically, turns to environmental and engineering approaches for pandemic remediation, especially when no vaccine is available. Employing highly effective virus-trapping and eradicating measures, including other engineering approaches, such as better air handling, ventilation and filtration that addressed early viral pathogen community spread could have helped ended the pandemic and this calls for future preparedness, now that all is believed righted.The development of improved PPE has been identified as a critical unmet need. Moreover, environmental science, which is more reliable than improving PPE and general virucidal approaches seem to be the more affective intervention human expectation of behavior change of compliance and follow-through suggests our approach would be a superior and more efficacious endeavor, coupled with educational considerations. Our progress toward improving PPE was severely hampered by disinformation and an interrupted supply chain. However, to date, these issues seem to have been only partially resolved. We suggest our approach will guide biomaterial development and greatly improved or enhanced PPE. Nevertheless, vaccine hesitancy and limited available treatment options remain an issue to improving outcomes. Therefore, basic understanding of SARS-CoV-2 infection and remediation is advancing. However, what is required is a clear stance of future viral pandemic preparedness, regardless of mechanisms of viral transmission. Beyond the immediate necessity for PPE and EPPE, the approach outlined in our project would aim to benefit the world against emerging pandemics and current or future viral outbreaks or resistant variants. For example, these approaches would work against the new strain of H1N1 swine flu (G4 EA H1N1), previously discussed. Getting up to speed to confront the crisis that now or will present itself and will involve innovative approaches that can be immediately applied. Our COVID proposals, which this contribution encompasses. Further, the approaches discussed on natural product coatings would not require immediate safety testing, as no ingestion would occur with a person or pet and would be safer if it happened as many of these compounds are currently in use or tested and approved as drugs and viral inhibitors. The off-use application could certainly be waived for emergency use authorization. The goal of these application has been to offer a biologic decoy to inhibit and or kill viruses by such means as cognate substrates or drugs and inhibitors can be made to bind virions tightly to the substrate and the coating are also fixed to the mask layers. For example, HA or the S-protein can lock virons in a configuration that prevents fusion of the cellular and viral membranes. In effect Authors contribute this is a trap and a cellular decoy. We hope this work is read and shared for the sake of future mankind over funding.


The experts agreed to name the clades using Roman numerals.The monkeypox virus was named upon first discovery in 1958, before current best practices in naming diseases and viruses were adopted. Similarly for the name of the disease it causes. Major variants were identified by the geographic regions where they were known to circulate.Current best practice is that newly-identified viruses, related disease, and virus variants should be given names with the aim to avoid causing offense to any cultural, social, national, regional, professional, or ethnic groups, and minimize any negative impact on trade, travel, tourism or animal welfare.Disease: Assigning new names to existing diseases is the responsibility of WHO under the International Classification of Diseases and the WHO Family of International Health Related Classifications (WHO-FIC). WHO is holding an open consultation for a new disease name for monkeypox. Anyone wishing to propose new names can do so here .Virus: The naming of virus species is the responsibility of the International Committee on the Taxonomy of Viruses (ICTV), which has a process underway for the name of the monkeypox virus.Variants/clades: The naming of variants for existing pathogens is normally the result of debate amongst scientists. In order to expedite agreement in the context of the current outbreak, WHO convened an ad hoc meeting on 8 August to enable virologists and public health experts to reach consensus on new terminology.Experts in pox virology, evolutionary biology and representatives of research institutes from across the globe reviewed the phylogeny and nomenclature of known and new monkeypox virus variants or clades. They discussed the characteristics and evolution of monkeypox virus variants, their apparent phylogenetic and clinical differences, and potential consequences for public health and future virological and evolutionary research.The group reached consensus on new nomenclature for the virus clades that is in line with best practices. They agreed on how the virus clades should be recorded and classified on genome sequence repository sites.Consensus was reached to now refer to the former Congo Basin  clade as Clade one (I) and the former West African clade as Clade two (II). Additionally, it was agreed that the Clade II consists of two subclades.The proper naming structure will be represented by a Roman numeral for the clade and a lower-case alphanumeric character for the subclades. Thus, the new naming convention comprises Clade I, Clade IIa and Clade IIb, with the latter referring primarily to the group of variants largely circulating in the 2022 global outbreak. The naming of lineages will be as proposed by scientists as the outbreak evolves. Experts will be reconvened as needed.The new names for the clades should go into effect immediately while work continues on the disease and virus names.https://www.who.int/news/item/12-08-2022-monkeypox--experts-give-virus-variants-new-namesAvailable from:


When the IDF was 300 mesh, the inhibitory rate of α-glucosidase was 61.34 ± 1.12%, and the inhibitory rate of α-amylase was 17.58 ± 0.33%. It had increased by 25.54 and 106.83%, respectively compared to the control treatment (CK) group. In addition, correlation analysis found that the particle size was highly negatively correlated with some functional properties of IDF (p < 0.05), and the content of cellulose was positively correlated with the functional properties of IDF except WHC (p < 0.05). To sum up, reducing particle size was suitable for the development of high value-added IDF products. This study also revealed the potential value of corn bran IDF and provided a new idea for the diversified application of IDF.This study was designed for determining the effect of particle size on the functional properties of corn bran insoluble dietary fiber (IDF). Results showed that some physicochemical properties were improved with the decrease in particle size. The structure of the IDF was observed by the scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The surface was found wrinkled and sparse, the particle size was smaller, the crystallinity of IDF had increased slightly, and more -OH and C-O groups were exposed. Moreover, the corn bran IDF with a smaller particle size had a better hypoglycemic effect  Dietary Fiber (DF) is a polysaccharide carbohydrate with low nutritional value, but it has a variety of benefits for human health and reduces the risk of diabetes , 2. It cCorn is the world's largest food crop in terms of total output and has immense economic and social value. Corn produces many by-products during its processing, such as corn cob, corn bran, corn gluten meal, and corn fiber , 8. In gUltrafine grinding has always been considered an efficient and green food processing technology , 12. TheIn this study, the IDF from corn bran was obtained by using enzymatic hydrolysis. The ultrafine corn bran IDF powder was prepared using an airflow pulverizer and sieved with different mesh sieves to obtain corn bran IDF in different particle sizes. This study aimed to explore the effect of particle size on the IDF's functions. It provides technical support for corn bran IDF as a functional ingredient for hyperglycemia and plays an active role in improving the added value of corn bran.5 u/g), saccharifying enzyme (1.5 × 105 u/g), and amylase (2 × 105 u/g) were purchased from Novozymes Biotechnology Co., Ltd. . Total Starch Assay Kit and Glucose Assay (ab65333) were purchased from Abcam Shanghai Trading Co., Ltd. . α-glucosidase (50 U/mg), and 4-nitrophenyl-α-D-glucopyranoside (PNPG) were purchased from Yuanye Bio-Technology Co., Ltd. . Cellulose(CLL)Content Assay Kit (AKSU007C), Themicellulose Content Assay Kit (AKSU008C), and Lignin Content Assay Kit (AKSU010U) were purchased from Beijing Boxbio Co., Ltd. .Corn bran was purchased in 2021 from Beijing Jingliang Co., Ltd. . and stored at 4°C for use. Alkali protease (2 × 10m/m)] was added, adjusted to pH 6.7 simultaneously, and left for enzymolysis for 2 h. The reaction was terminated in the same way as above. After the mixture was cooled, it was centrifugated at 4,000 rpm for 15 min, and the residue was washed with 95% ethanol four times and dried at 45°C for 6 h to obtain the IDF from corn bran.The preparation of corn bran IDF was referenced from Zhang et al. . Defatte was used to crush the IDF from corn bran, and the powder was sieved with different mesh sieves from 200 to 400 mesh . The size of the sieve pores were 75, 63, 53, 45, and 38 μm respectively. The powder of the control (CK) group was sieved with 60 mesh . The evaluation of the particle size was undertaken using a laser diffraction particle size analyzer .The ultrafine pulverizer The WHC was determined using the process suggested in López-Marcos et al.  with somThe OHC was determined by consulting the process suggested in Zheng et al.  with somWw is the wet weight of the sample, and Ws is the weight of the sample.where The WSC was determined using the process suggested in Zheng and Li  1.0 g ofV1 is the hydrated volume, V0 is the initial volume, and Ws is the weight of the sample.where To determine CAC and CLAC, we referenced Yang et al.  1.0 g ofN1 is the mass of cholesterol before absorption, N2 is the mass of cholesterol after absorption, and Ws is the weight of the sample.where About 200 mg of the sample was mixed with 20 mg sodium cholate or sodium taurocholate in 20 ml of buffer (pH 7.0), shaken well, and incubated at 120 rpm at 37°C for 2 h. It was then centrifugated at 4,000 rpm for 15 min, and the absorbance of the supernatant was measured by the furfural colorimetric method and calculated as eqn (5):C1 is the initial concentration of cholate, C2 is the terminal concentration of cholate, 20 is the volume of buffer, and Ws is the weight of the sample.where The samples were analyzed under a SU8020 scanning electron microscope  at an accelerating potential of 5.0 kV.−1 was used for the XRD.The XRD was detected by the D8 Advance diffractometer  with Ni-filtered Cu-Kα radiation . A 2θ range from 5° to 70° at a speed of 0.02° s−1.About 5 mg of IDF samples were mixed with 100 mg KBr and the FT-IR of the sample was analyzed under a Spectrum Two Fourier transform infrared spectrophotometer , at a range of 400–4,000 cmAbout 1.0 g of the IDF samples were weighed and mixed with 100 ml of glucose standard solution . The mixture was incubated at 120 rpm at 37°C for 6 h. Then it was centrifugated at 4,000 rpm for 15 min. The content of glucose in the supernatant was measured according to the instructions in the kit, and calculated using the formula (6):Ni is the amount of initial glucose, Ne is the amount of glucose at the end of the reaction, and Ws is the weight of the sample.where The method was referenced from Zhu et al.  with somIt was determined using the previous method . A sampl2CO3 (0.2 mol/L) was added immediately after 30 min. The absorbance was measured at 405 nm after mixing. The inhibition rate of the sample to α-glucosidase was calculated as follows:The method was adapted from Chen et al.  with som1, A2, A3, and A4 are the absorbance values of blank control tube, blank tube, sample tube, and sample control tube at 405 nm respectively.Where Ap < 0.05) was regarded as statistically significant. The Pearson correlation between physical , CLAC (SC and STC), GAC(50 mmol), GDRI, Starch digestion inhibition, and α-glucosidase activity inhibition) were calculated.All the data were measured three times and showed as “mean ± standard error.” The data were analyzed by Duncan's test and ANOVA using SPSS 20.0 software. A probability level of 5% , and area average diameter  of corn bran IDF after ultrafine pulverization were significantly decreased (p < 0.05). The D98 value of corn bran IDF sieved with 200–400 mesh, compared with the CK group, was decreased by 38.38, 57.06, 72.86, 77.78, and 83.44%, respectively. The specific surface area of IDF increased significantly (p < 0.05) by 14.58, 31.25, 120.83, 131.25, and 225.00%, respectively , (p < 0.05), and WSC and OHC were significantly increased when the mesh was >250 mesh (p < 0.05)  and intestinal (pH 7) environments. The CAC was higher under neutral than acidic conditions, and the CAC of corn bran IDF was significantly increased (p < 0.05) when the particle size was larger than 300 mesh (p < 0.05) , . The WHC < 0.05) . Among t < 0.05) , while p < 0.05) . The cha < 0.05) . The CAC300 mesh . The CLA < 0.05) , indicat < 0.05) , where sUnder the same magnification of scanning electron microscope, the CK group had a larger particle size, more obvious surface folds, irregular edge, and non-uniform porous structure . Due to The corn bran IDF has an obvious diffraction peak around 22°, and a weak diffraction peak around 5°~15° . The ove−1, which was generated by the O-H stretching vibration of cellulose or hemicellulose  at any glucose concentration, indicating that ultrafine grinding had a positive effect on GAC. The glucose in the dialysate was enhanced constantly with time (p < 0.05), and the inhibitory activity of α-glucosidase was stronger than α-amylase (Some studies have shown that IDF has hypoglycemic properties. The IDF has a great glucose absorption capacity. With the increase in glucose concentration (10–50 mmol/L), the adsorption characteristics of IDF gradually increased . The maxith time . Compareith time . The inh-amylase . When th and CAC (pH2), GAC (50 mmol/L), GDRI, and starch digestion inhibition were all high negative r values >0.95. The correlation between D and CAC (pH2), and GDRI yielded high negative r values of 0.992 and 0.966, respectively. The correlation between the content of cellulose and CAC (pH2), CLAL (SC), GAC (50 mmol/L), starch digestion inhibition, α-glucosidase activity inhibition, and α-amylase activity inhibition had high positive r values >0.95. The correlation between the content of hemicellulose and CAC (pH2) generated high negative r values of 0.981. Correlations between the content of lignin and CAC (pH2), and GDRI yielded high negative r values of 0.990 and 0.955 respectively.The Pearson correlation between physical and functional properties was calculated and the results are shown in , and D were all decreased significantly (p < 0.05), but the specific surface area increased significantly (p < 0.05). These illuminated the shear, the impact. The impact and other forces generated in the process of airflow ultrafine pulverization could reduce the particle size of the powder effectively. However, it is possible that the ultrafine pulverization destroyed the structure of fibers simultaneously, leading to the redistribution of fiber components. Cellulose content was significantly increased and the content of hemicellulose and lignin was decreased, compared with CK (p < 0.05) (Studies have shown that particle size can directly measure the effect of ultrafine grinding . In this < 0.05) . The res < 0.05) . There wp < 0.05). Those results were possible because surface properties were changed, exposing lots of hydrogen bonds and dipole forms, thereby enhancing the WSC of the ultrafine powder. Additionally, the specific surface area increased, which may have promoted the WSC. The decrease in particle size also resulted in more exposure to some lipophilic groups, which enhanced the OHC of the ultrafine powder. In addition, the reduction of the particle size of IDF after ultrafine grinding impacted the binding ability to cholesterol. It is generally believed that the main mechanism of DF to reduce blood lipid and cholesterol is to absorb fat, increase the amount of fat excretion in feces, bind bile acid, and promote the conversion of cholesterol into bile acid. Several studies have shown that cellulose is more hydrophobic than hemicellulose in the major constituents of IDF , exposing more functional groups, such as -OH and -COOH, so the van der Waals and hydrogen bonding forces could effectively adsorb glucose molecules , GAC 50 mmol/L), GDRI, and starch digestion inhibition  had the best quality, such as OHC, WSC, CAC, and CLAC. The structure of IDF was observed by SEM, X-ray, and FT-IR. It was found that the surface was porous and uneven and the structure of the fiber was destroyed by ultrafine grinding. The particle became smaller and the crystallinity of IDF increased slightly. More -OH and C-O groups were exposed, which could adsorb glucose effectively. At the same time, the IDF surface enzyme inhibitors effectively reduced the degree of starch digestion and controlled postprandial blood glucose levels. In addition, it was found by correlation analysis that the particle size was highly negatively correlated with some functional properties of IDF, and the cellulose content was positively correlated with the functional properties of IDF except WHC. To sum up, reducing particle size was suitable for the development of IDF in high value-added products.To explore the effect of particle size on the IDF and to expand its application channels, in this study, the corn bran IDF with different particle sizes was compared and analyzed for its physicochemical properties, microstructure, and The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.XZ and XL were responsible for the design and management of the entire experiment. JW provided a part of the test route. FZ performed experimental methods and collected the data. CJ and RW analyzed the data and wrote the manuscript. All authors have read and agreed to the manuscript for publication.This work was supported by cooperation research on the Key Technology of Corn Functional Sugar Production (2019ZX06B02), Heilongjiang Key R&D Program Guidance Project (GZ20210097), Heilongjiang One Billion in Major Engineering and Technology Sub-project (2021ZX12B09-4), and Talent Foundation of the Central Government Supporting Local Universities (2020GSP08).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Aedes aegypti mosquitoes and causes the disease known as dengue. In a trial published in The New England Journal of Medicine, Utarini and colleagues report that release of wolbachia-infected A. aegypti populations in a dengue endemic area reduces the number of symptomatic cases and of hospitalisations.Dengue virus is transmitted by  Aedes-borne virus is emerging into new geographical areas and the incidence has increased significantly in the last decades globally, placing dengue as one of the top ten global health threats.According to the World Health Organisation, dengue is estimated to affect 100–400 million people worldwide every year, putting considerable strain on health services in low- and middle-income countries. Global warming, among other factors, means that this A. aegypti mosquitoes, public health interventions focus on vector control measures. One possibility is to control infection of the vector, but this has so far not been trialled with enough success. It is known that introgression of A. aegypti with the bacteria Wolbachia pipientis confers resistance to infection of the mosquito with dengue virus. Utarini and colleagues have performed a cluster-randomised controlled trial to assess the efficacy of releasing A. aegypti mosquitoes, infected with the wMel strain of W. pipientis, on reducing the incidence of dengue and hospitalisation from the disease, in the city of Yogyakarta in Indonesia1.Since the four dengue virus serotypes are transmitted to humans mainly by wMel-infected mosquitoes, and twelve others to serve as controls in which no mosquitoes were released. Primary health care facilities in the trial area monitored patients for acute fever with no signs of other non-arboviral disease, and recruited individuals between 3 and 45 years old. The primary endpoint was virologically-confirmed dengue virus infection of any severity, and the safety end points included hospitalisation within 21 days of enrolment.Between March and December 2017, 12 geographic clusters were randomly assigned to the intervention of releasing In total, 3721 participants were recruited in intervention clusters, and 4423 in control clusters. In the intention-to-treat analysis, the incidence of virologically-confirmed dengue was 77% lower in participants who lived in intervention clusters compared to participants who lived in control clusters, and this was similar for all four dengue virus serotypes. In addition, the intervention resulted in an 86% protective efficacy against hospitalisation.A. aegypti significantly reduces symptomatic disease and hospitalisations in an endemic urban area, showing promise for vector-mediated control of dengue. These results potentially have broader implications for the control of other Aedes-borne virus infections, such as those caused by Zika, Yellow fever, or Chikungunya viruses.These results demonstrate that release of Wolbachia-infected


The World Health Organization (WHO) recently declared the monkeypox virus a Public Health Emergency of International Concern (PHEIC). As the cases of the COVID-19 pandemic start to get under control, we have seen the monkeypox virus, found predominantly in Africa, spread in non-endemic countries worldwide. In the 1970s, after the smallpox virus eradication and the vaccine's discontinuation, the monkeypox virus infection started to gain attention. The first United States outbreak happened in 2003; since then, more sporadic cases of monkeypox have gained media attention. With cases spreading worldwide, without epidemiological links with outbreaks among men who have sex with men (MSM), it warrants urgent public health control measures to contain the spread of the monkeypox virus and investigate the underlying pathophysiology, including genetic modification of the virus. This review highlights the epidemiology, transmission, pathogenesis, clinical manifestation, diagnosis, prevention, and management of the current human monkeypox virus infection. Monkeypox belongs to the same genus that causes smallpox. Many common viruses belong to this genus, including cowpox, horsepox, camelpox, and alaskapox. The variola virus is the most common and well-known member among all the viruses present in this genus. The World Health Organization (WHO) formally declared the eradication of smallpox in 1980 [Even though the monkeypox virus is homologous to the smallpox virus, the mortality risk and contact transmission from monkeypox are substantially lower than that of smallpox ,3. HowevMethodologyA iterature search for monkeypox was performed using PubMed, ScienceDirect, and Google Scholar search engines. The search syntax included the following terms: "Monkeypox" and "origin," "spread", "symptoms", "prevention", "treatment", "vaccine", OR "risk to the healthcare worker". Four physician authors reviewed the literature, and the information is summarized in this article for simplicity of comprehension.EpidemiologyMonkeypox was initially isolated in Denmark from monkeys used in the resource of poliovirus in 1959 . Some spImmunization against smallpox also protects humans against the monkeypox virus; after the smallpox vaccination program was abandoned due to the disease's eradication, the WHO was concerned about greater susceptibility and incidence of monkeypox infection in the contemporary population. A survey conducted between 2005-2007 in the Democratic Republic of Congo showed that monkeypox infection in this country rose by 20-fold [Early May 2022 saw the isolation of the first cases of the current major monkeypox outbreak in Europe , and sinThe transmission of the monkeypox virus can happen in two waysAnimal to Human TransmissionDuring this transmission, humans come in contact with the virus via infected animals' body fluids or by an infected animal's bite. It can also be transmitted when consuming raw/minimally processed meat from an infected animal. This raw or minimally processed meat consumption is also known as bushmeat. The monkeypox virus in Africa is typically found in animals like squirrels, rats, and monkeys .Human to Human TransmissionHuman transmission can occur in different ways, which include direct contact, indirect contact, respiratory droplets, and vertical transmission -15.Direct contact: Transmission occurs when a person comes in direct contact with the infection source, for example, infected body fluids or scabs. The ongoing outbreak of monkeypox in the world, especially in non-endemic countries, is thought to be due to the person's direct contact, mostly during sexual activities . A non-iIndirect contact: Transmission occurs when materials like clothes or linens come in contact with infected material like bodily fluids. A non-infected person can then come in contact with these materials and get infected .Respiratory transmission: Transmission occurs via respiratory secretions/droplets from coughing and sneezing .Vertical transmission: Transmission occurs upon a fetus being exposed to the virus from her mother. The virus is known to cross the placenta and can lead to congenital monkeypox infection in newborn babies .Future studies are required to better comprehend the role of virus transmission through genital fluids versus other secretions/forms . Hence, PathogenesisMonkeypox virus can be transmitted via animal or human contact, as described above. The virus enters the host, replicates at the entry site, and circulates via the lymphatic system. This leads to systemic infection, also known as primary viremia. The virus will now start replicating in the lymphoid organs and distant lymph nodes, resulting in infection of the epithelium and tertiary organs, producing mucosal and skin lesions, which results in the clinical manifestation of this virus .Clinical manifestationsThe incubation period for the monkeypox virus can range from five days to three weeks . MonkeypHowever, some patients can get the rash without going through the prodromal phase . The rasDiagnosisPatients with typical rash and symptoms such as fever/chills should be suspected of having monkeypox infection, particularly if they have risk factors like recent travel to areas endemic for monkeypox. Additionally, patients who experience symptoms of sexually transmitted infections, such as genital rash, and who do not improve after receiving empiric treatment should be treated with a high degree of suspicion.Laboratory evidence such as that of the predominance of the virus or IgM (immunoglobulin) antibodies must be present if monkeypox is suspected in the patient. Viral or serological testing can be used to determine this.Orthopoxvirus is suspected of having monkeypox infection per CDC guidelines for the 2022 outbreak of the monkey virus. Confirmation of the virus can be made when monkey virus DNA can be demonstrated by PCR.Viral testing includes a polymerase chain reaction (PCR) test performed on the infected lesion. A patient whose PCR test result shows positive Orthopoxvirus IgM & IgG antibodies, typically developing five to eight days after the rash [Serological testing for the detection of monkeypox can be used if viral testing such as PCR is unavailable. The patient infected with the monkeypox virus will have elevated anti-the rash .Monkeypox virus-infected cells have a brick-like form on electron microscopy identical to variola or vaccinia virus-infected cells, as seen in Figure TreatmentThe majority of monkeypox virus patients have mild symptoms and should make a full recovery without any professional attention. However, some patients could need hospitalization and supportive care due to nausea, vomiting, the potential for dehydration, or pain management. Antiviral medication is advised for those people who, as was previously noted, are at high risk of contracting a severe illness.Multiple antiviral medications are available which can be used for the treatment of monkeypox. Some of these medications were developed for treating smallpox in animals but are expected to have the same activity against monkeypox ,25. Of all the antivirals available, tecovirimat is a treatment of choice for most cases. Patients with severe disease may also benefit from dual therapy of tecovirimat and cidofovir. Public health officials should be made aware when starting these treatments.TecovirimatOrthopoxvirus and therefore blocks the interaction of the virus with the host cell. This leads to inhibition of the infectious virus particles and prevents the host cell from getting infected. In 2018, the United States (US) approved tecovirimat to treat the smallpox virus [Tecovirimat is available in both an IV and oral form. This medication inhibits the VP37 protein present in ox virus . Tecovirox virus . If treaox virus ,10. CidofovirThis medication is effective against monkeypox in animal studies . HoweverOther US boxed warnings: This medication can be carcinogenic and teratogenic based on animal studies. Also, patients are at risk of neutropenia with this medication; therefore, the patient's neutrophil count must be monitored when receiving this medication. There is a risk for metabolic acidosis along with hepatic impairment and pancreatitis. Cidofovir should be avoided in pregnant females as it can be teratogenic; however, if use is warranted, systemic therapy should be avoided during the first trimester if possible . It is nBrincidofovir:This medication is similar to cidofovir but likely has fewer side effects. This medication is a lipid conjugate that is converted to cidofovir intracellularly, which is then further converted to cidofovir diphosphonate, an active metabolite of cidofovir. Cidofovir diphosphate causes selective viral DNA inhibition, suppressing the virus application. Significant side effects include hepatotoxicity. Upon initiating this medication, patients with hepatic impairment should closely monitor their liver functions.  If a patTrifluridine:This medication can be used to treat and prevent corneal and conjunctival involvement in patients with monkeypox lesions involving the eye. This medication comes in topical antibiotic drops or ointment, which can be applied every four hours for seven to 10 days ,36. No dPreventionFor prevention, a two-fold approach is needed. The first goal should be to promptly treat those infected and provide post-exposure management to minimize the onset of illness. The second goal will be at the public health and policy/ administrative level with increased funding and making diagnostic tests and vaccine availability a priority. Increased community awareness and wider surveillance of current cases and exposure is the first step toward preventing the spread ,38. TherMinimizing or avoiding stigmatization is needed to prevent discrimination and optimize disease response. Especially in the LGBTQ+ community and the public in general, aggressive educational campaigns regarding the transmission and spread will help minimize the stigma and, thereby, the hesitancy to seek help . The stiKey preventive measure is related to minimizing contact with the lesions, as close and prolonged contact appears to be the primary mode of transmission . Social Pre-exposure prophylaxis vaccineThe Advisory Committee on Immunization Practices (ACIP) recommends pre-exposure prophylaxis by using the modified vaccinia Ankara (MVA) vaccine for individuals who are at high risk due to occupational exposure to orthopoxvirus infections , for exaPost-exposure risk assessmentPeople should watch closely for symptoms for at least 21 days post-exposure with a monkeypox patient. If a person remains asymptomatic, they can resume their normal activities; however, if they start to experience symptoms, they should quarantine themselves and seek further medical attention from their primary care provider or the health department. There are three categories of risk of exposure .High-Risk ExposureCDC considers patients as high-risk exposure if they had: a) contact with infected patient's skin, mucous membranes, skin lesions, and/or body fluids, for example, sexual contact, contact with patient's saliva to the eye or oral cavity of an uninfected individual, contact with contaminated materials like clothes. b) Being within six feet of an infected patient undergoing procedures that increase the risk of creating aerosol from oral or skin lesions without wearing proper N95 and eye protection, for example, dental procedures, or shaking soiled infected clothes.Intermediate Risk ExposureA non-infected individual within six feet of an individual infected with monkeypox without wearing a mask for three hours or more is considered intermediate risk. Individuals should be wearing at least a surgical mask. An additional intermediate degree exposure is when a non-infected person using only gloves and not donning a gown comes in contact with an infected patient's bodily fluids, skin sores, or dirty clothing.Low-Risk ExposureCDC considers low risk when a non-infected individual comes in contact with an infected patient a) while taking all proper precautionary measures when entering a patient's room, b) without wearing eye protection regardless of the duration of exposure, and c) is within six feet for less than three hours, and not wearing a mask.CDC recommends that individuals exposed to the monkeypox virus refrain from donating organs, blood, or breastmilk for at least 21 days to ensure they do not develop symptoms .Post-exposure treatmentIndividuals exposed to the monkeypox virus should consult their public health authority, which will determine treatment plans depending on the exposure risk mentioned above. Individuals eligible for prophylactic vaccinations should be vaccinated within four days of exposure to achieve the maximum benefit. Even though the vaccine can be given for up to 14 days post-exposure, if given between four and 14 days post-exposure, it minimizes the symptoms and does not prevent infection .In individuals with high-risk exposure to monkeypox, per CDC guidelines, postexposure modified vaccinia Ankara (MVA) vaccination is required. Immunocompetent individuals may use the ACAM2000 vaccine as well. According to CDC guidelines , post-exVaccinia Immune GlobulinPatients who are immunocompromised and exposed to the monkeypox virus may require the use of vaccinia immune globulin. CDC must be contacted for this agent to be available for the patient if needed.Post-exposure vaccinationThere are two types of vaccination available that can reduce the risk of monkeypox infection.Modified Vaccinia Ankara (MVA) VaccineSold under the trade name Jynneos  in the United States (US), it is a live, nonreplicating vaccine. This vaccination has an excellent safety profile and can even be used in immunocompromised patients and patients with skin disorders. This vaccine requires two doses subcutaneously, which are administered four weeks apart. This vaccination is made from the nonreplicating vaccinia virus. Common side effects of the MVA vaccine include headache, myalgia, pain at injection site, and lymphadenopathy that last only a few days post-vaccination .ACAM2000ACAM2000 is a replication-competent smallpox vaccine. This vaccination should be used only in healthy, immunocompetent, and nonpregnant patients with a high risk of exposure. This vaccination is associated with more side effects when compared to the MVA vaccine because ACAM2000 requires an infectious dose on a bifurcated sterile needle that is penetrated into the epidermis of the deltoid region of the arm about 15 times. This process is known as scarification. After two to five days of vaccination, a papule will form, becoming a vesicle after a few more days . The vesOrthopoxvirus, also known as monkeypox virus, was initially discovered in the 1950s. Previously, this virus was primarily confined to Central and West Africa. However, monkeypox virus infection has gradually expanded worldwide with the termination and eradication of the smallpox vaccine and virus. Therefore, on July 23, 2022, the WHO recently designated the monkeypox virus as a public health emergency of international concern (PHEIC). Attributed to the rise in cases, the CDC advises clinicians and other healthcare providers to remain vigilant and report to local health departments if they discover any patients infected with the monkeypox virus. These local health departments can then reach out to the CDC and formulate a strategy for individuals who had direct contact with these patients. Since this infection can spread via droplets or skin-to-skin contact, the healthcare professionals treating a patient suspected of monkeypox should use standard contact and droplet precautions. A crucial lesson is avoiding close contact with suspected patients to reduce transmission. Community education to maximize prevention efforts and destigmatizing to minimize barriers to seeking help are key to containment. The


Discovered in 2004, CAstV consists of two genogroups with an expanding subgroup because of the diversity exhibited in its viral capsid sequence. Despite these findings, there exists a dearth of knowledge on its pathogenesis. This review highlights the pathogenesis and development of  Astroviridae family. They are ubiquitous in healthy and sick chickens and are capable of causing significant economic losses during infection. The prevalence and incidence of the virus have been reported in the UK, the US, Germany, China, Finland, Poland, Nigeria, South Africa, the Netherlands, and the Middle East (Chicken astroviruses (CAstVs) are small, round, non-enveloped, positive-sense, single-stranded RNA viruses in the avian astrovirus genus of the dle East –7. In thdle East , 9. Sincdle East , new strdle East –17.Previously, infections with astroviruses were assumed to be species specific; however, there are pieces of evidence strongly suggesting transmission between the avian species, such as turkey, chicken, and duck astroviruses, while exhibiting some share of identity in their genetic features , 18. In Despite the progress made in the detection and characterization of novel CAstVs , 21, 22,Like the turkey model, the murine model  was discovered by researchers in mice in 2012. However, in contrast to TAstV, diarrhea was absent in the infection caused by MuAstV. This finding is expected in mice because colitis must be induced before diarrhea , 30. MorRecently, studies in chickens have helped to elucidate the molecular and cellular attributes of CAstV conditions , 31. ThiShortly after the discovery of astrovirus in 1975, small round virus particles with astrovirus morphology were recorded in domestic animals, particularly calves and lambs with gastroenteritis , 33 and Clinical manifestations vary from diarrhea (3–4 days after infection), to runting-stunting syndrome (6–12 days post-hatch), to weak and runted chicks in cases of hatchery disease or WCS, and to death, as a result of nephropathy and visceral gout, or in severe cases of WCS , 31, 38.Chicken astrovirus infections are of clinical and economic concern due to their negative impact on production, owing to the increased severity of clinical symptoms and extra-intestinal involvement. Although other viruses have been implicated in cases of RSS, underperformance, and growth checks, recent studies have identified CAstV as the sole etiologic pathogen responsible for the condition in chickens and turkeys , 20, 39.Furthermore, over the years, severe kidney disease and gout in chickens were associated with infectious bronchitis virus (IBV), avian nephritis virus (ANV) , and nutritional or managemental factors, but recently, these symptoms have been associated with CAstV , 43, 44.On the other hand, kidney disease has also been observed in chickens with WCS in addition to the lesions seen on the feathers, intestine, and liver , 26, 38.There are numerous similarities between the astrovirus infections in chickens and other animal species, including humans. Most animals infected with astrovirus, including humans, calves, piglets, turkeys, and lambs, develop diarrhea similar to chickens , 53–57. in vitro system, such as embryonated chicken egg or cell culture, is complex and unpredictable  (MB1 to 3) and HAstV-VA/HMO (Virginia/Human-Mink-Ovine-like) strains were not supported by any cell line for propagation, similar to the majority of other avian and mammalian astroviruses , 62. HowIn Kang et al.  study, cin situ hybridization (FISH) of CAstV suggests that the replication of the virus is restricted to the enteric enterocytes. In the epithelial cells of the villous, the identification of the viral RNA was explicit within the first 12 hpi (Fluorescent In an experimental infection study using SPF day-old chickens, individual degenerating enterocytes of the small intestines were apparent along the basal edge of the villi by 3 dpi and continued through 5 dpi at the crypt epithelial cells. By 5 dpi, CAstV localized primarily in the small intestine. By 6 dpi, mild shortening of the villi was prominent, as well as the occasional clusters of necrotic enterocytes along the villous base correlating with the infection . ReplicaFurthermore, immunity-related studies of CAstV showed that the relative levels of gene expression of some of the important cytokines are different in the various tissue samples, which include thymus, jejunum, liver, and spleen, of the chickens infected with CAstV-WCS isolates . It was via Th1-mediated response.Furthermore, in Nuñez et al.  study, tWith all these fascinating and limited findings and works on the pathogenesis of CAstV, it will be quite interesting to study the virus further.in vivo. Even with all these advances in the study of CAstV and other astroviruses, we, nonetheless, confront hurdles in having a standardized animal model that will elucidate the pathogenesis of astrovirus and the subsequent production of the vaccine, therapeutics, and cross-species infections. Unlike HAstV, chickens or turkey poults can perfectly be utilized for the studies related to CAstV pathogenesis and hence serve as a basis for further research on astrovirus.With much still needed to be worked on, particularly on the pathogenesis of the virus, there has been progress in the areas of molecular characterization and typing of the virus. The recent discovery of Bv and Bvi subgroups reveals that CAstV-related conditions are widespread and affect the commercial poultry industry to a much greater extent than previously anticipated . In the AR: conceptualization, writing-preparation and writing of the first draft, writing-review and editing. AO: concept, formatting, initial review, approval for publication and agree with final publication of the article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cryptococcus species are a major cause of life-threatening infections in immunocompromised and immunocompetent hosts. While most disease is caused by Cryptococcus neoformans, Cryptococcus gattii, a genotypically and phenotypically distinct species, is responsible for 11–33% of global cases of cryptococcosis. Despite best treatment, C. gattii infections are associated with early mortality rates of 10–25%. The World Health Organization’s recently released Fungal Priority Pathogen List classified C. gattii as a medium-priority pathogen due to the lack of effective therapies and robust clinical and epidemiological data. This narrative review summarizes the latest research on the taxonomy, epidemiology, pathogenesis, laboratory testing, and management of C. gattii infections. Cryptococcus can cause life threatening infections in both immunocompromised and immunocompetent hosts. Although most disease is caused by Cryptococcus neoformans, C. gattii—a genotypically and phenotypically distinct species—causes 11–33% of invasive cryptococcosis globally [C. gattii is associated with 28 day case fatality rates in range 10–25% [C. gattii as a medium priority pathogen in light of the poor availability of safe and effective therapies and a lack of robust clinical and epidemiological data [globally ,3. Even e 10–25% ,5,6,7. TCryptococcus gattii infections—contrasting this, where relevant, with what is known about the more common pathogen, Cryptococcus neoformans. Data, as far as possible, are from the last 10 years. Only English-language publications were included.We conducted a narrative review of the literature, summarising what is new in epidemiology, pathogenesis, diagnosis, and management of Cryptococcus neoformans and Cryptococcus gattii are haploid encapsulated yeast-like fungi of the class Trellomycetes [Cryptococcus neoformans includes two varieties, Cryptococcus neoformans var. grubii and Cryptococcus neoformans var. neoformans, though further sub-divisions have been proposed; Cryptococcus gattii is a separate species [Cryptococcus neoformans and Cryptococcus gattii complexes [omycetes . First domycetes . Cryptoc species ,10,11. Tomplexes .Cryptococcus spp. were distinguished by serotype with serotypes A, B and C recognized two decades before serotype D [LAC1) and capsule gene (CAP64) [Cryptococcus neoformans: A is C. neoformans var grubii and D is var neoformans. Serotypes B and C are Cryptococcus gattii. Hybrids also exist. A minority of Cryptococcus spp. (ranging from 2–21%), are acapsular or pauci-capsular, and so untypeable [Historically, rotype D . Serotyp (CAP64) ,14,15. Stypeable ,17,18.C. gattii (VGI-VGIV) and C. neoformans  , VNIII (hybrid of serotypes A and D), VNIV–serotype D) [The advent of molecular taxonomy has revolutionized fungal nomenclature. Various techniques have been used including PCR-fingerprinting, Restriction Fragment Length Polymorphism (RFLP), Amplified Fragment Length Polymorphism (AFLP) and Multi-Locus Sequence Typing (MLST) to identify distinct lineages within the two species complexes: otype D)  (see TabC. neoformans and C. gattii be divided into 7 sibling species based on the phylogenetic (evolutionary) species concept. Namely, for neoformans: Cryptococcus neoformans (genotype VNI), Cryptococcus deneoformans (genotype VNIV), plus C. neoformans × C. deoneoformans hybrid (genotype VNIII). For gattii: Cryptococcus gattii (genotype VGI), Cryptococcus deuterogattii (VGII), Cryptococcus bacillispora (VGIII), Cryptococcus tetragattii (VGIV), and Cryptococcus decagattii [C. gattii discovered in Zambian woodland environments in association with nitrogen-rich middens of a small mammal known as Hyrax, has been designated VGV, and C. decagattii as VGVI [Adding a further genotype based on a single clinical isolate from Mexico, Hagen et al. in 2015 proposed that  as VGVI ,22.C. neoformans and C. gattii should be considered species complexes, supported by clinical, epidemiological and ecological data, or divided into separate clades (species) with corresponding changes in nomenclature, based on genotyping alone, without clearcut biological differences [C. gattii lineage in Zambian woodlands introduced above suggests that further lineages will be discovered [Debate continues within the scientific community as to whether ferences ,20,23. Iferences  and lateferences  that spescovered .URA5, CAP59, GPD1, LAC1, SOD1, PLB1, and IGS). A database of quality-controlled reference sequences is available at https://mlst.mycologylab.org/ (accessed on 30 June 2022). and in the CBS-KNAW database ). As of 30 June 2022, this data base contained 566 entries for C. gattii and 662 for C. neoformans.MLST-based DNA Barcoding, which uses short diverse genetic sequences that are stable and unique to a given species, is currently the gold standard for cryptococcal typing ,24,25. AC. neoformans and C. gattii can be distinguished readily [Accurate species identification from fungal colonies can also be achieved reliably and rapidly by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS)  with min readily ,26,27. HC. gattii, may have spread from Australia and Northern Brazil to North America and Canada [C. neoformans, ST5 is the predominant serotype in China and Taiwan, ST93 in Brazil, ST41 in Japan and the US, with greater diversity in African countries [MLST has revealed geographical associations with clonal populations with increased heterogeneity possibly related to the origins of the species; for example, d Canada ,29 whereountries ,31,32.C. neoformans was published in 2005 [C. neoformans (NCBI accessed 30 June 2022). This has enabled further elucidation of origins, evolution, and genetic variation amongst the species complexes [C. gattii isolates in Zambia, and sub-lineages VNBI and VNBII within VNB of sub-Saharan African isolates associated with phenotypic differences, as well as the new designation of VGVI (putative C. decagattii) [Despite the value and comparatively low cost of MLST, the highest resolution is achieved with whole genome (next-generation) sequencing (WGS or NGS). This allows greater discrimination between strains and offers a method for species identification, detection of drug resistance mutations and epidemiological information. WGS has broadly confirmed the relationships between the different genotypes identified by MLST. The first whole genome sequence for  in 2005 . There aomplexes ,34. Assoomplexes ,36. Becaomplexes ,37. Noneagattii) ,20,21.C. gattii and C. neoformans species complexes. For clinical purposes, the use of species complexes is the more useful terminology and will be used from this point. Meanwhile, important research continues into the implications of different genetic groupings.In summary, debate persists regarding the delineation of species within both C. gattii and C. neoformans are adapted to different ecological niches and exhibit differences in epidemiology, clinical features, and virulence mechanisms [chanisms ,39.C. gattii, often eucalypts but including a huge range from oaks to baobabs [C. neoformans, on the other hand, is primarily associated with weathered pigeon guano.Several arboreal species have been identified as the predominant environmental reservoir of  baobabs . C. neofC. gattii infections occur predominantly in Australia, British Columbia, Canada, the Pacific Northwest of the USA, parts of South America and Africa. Molecular type VGI, has a global distribution but is most prevalent in Africa, Australia, and Europe. Molecular type VGII occurs globally but is mostly reported from Australia and the Americas. Molecular type VGIII is concentrated in, but not limited to, the Americas. The relatively rare molecular type VGIV has been reported in southern Africa and India, while the very rare molecular type VGVI has been reported from Mexico [Despite potential sampling bias across the globe, evidence to date indicates that m Mexico ,21,40,41There is some evidence that subgroups (subclades) within the VG lineages are also geographically defined, for example VGIa is found in Australia and the Pacific Northwest of the US, whereas VGI b has been found in Zambia; VGII a and c predominate in the Vancouver area and the Pacific Northwest of the US whereas VGIIb has been reported in far Northern Australia. These associations may reflect microevolution within these lineages over time.C. gattii. Modelling performed by Cogliati et al. determined that in Europe, C. gattii was concentrated along the Mediterranean coast, with its distribution limited by low temperatures during the coldest season, and by heavy precipitations in the driest season; C. neoformans var. grubii colonized the same areas but it tolerated cold winter temperatures and summer precipitations better [C gattii from 1980 to 2009 in the same region followed by doubling of the potential environmental niche in 2010–2019 and a predicted further extension inland from the coastal Mediterranean basin as a result of climatic change and global warming [Interest has recently turned to environmental factors affecting the distribution and virulence of fungal species, including s better . More ex warming .C. gattii, the discovery of VGV coexisting with VGI and VGII in Zambia in an entirely new ecological niche, namely, middens of the Southern tree hyrax (Dendrohyrax arboreus) [Cryptococcus.In relation to evolution of rboreus)  is of grrboreus) . They haC. gattii infection occurred predominantly in immunocompetent people, evidence increasingly points to potential immune and genetic factors predisposing to infection. In Australia the incidence of cryptococcosis in aboriginal populations is 10.4/million/year compared with 0.7/million/year in non-indigenous populations, and the difference cannot be wholly explained by differences in places of domicile or work [C. gattii infection [C. gattii.Although it was traditionally believed that  or work . In the  or work ,47. Subtnfection ,49. OverC. gattii infections, clinicians must consider the possibility of an underlying immune defect. Although many major causes of immunocompromise may be obvious on history taking, such as transplant or haematological malignancy, others require specific questioning about history of prior infections, family history of unusual infections, early deaths and/or malignancies. Positive findings may indicate further testing is desirable, such as blood smear/film, CD4/CD8/natural killer (NK) cell subsets by flow cytometry, immunoglobulin levels, complement testing and others. Where inborn errors of immunity are suspected, genetic testing will be required, and a clinical immunologist should be involved in discussions.When dealing with C. gattii is less likely to present with CNS involvement (varying by genotype), when it does, there is a higher incidence of CNS imaging abnormalities, mass lesions and hydrocephalus requiring neurosurgical intervention. There appear to be significant differences in cerebrospinal fluid (CSF) examination between the two species, with C. gattii CNS infections demonstrating lower CSF glucose and protein, higher median white blood cell counts and more frequent India ink positivity. Immune reconstitution inflammatory syndrome (IRIS) is more frequent in C. gattii infections than C. neoformans. Despite all this, CNS C. gattii infection has a lower mortality rate than C. neoformans. It must be noted, however, that mortality in patients with cryptococcal infections is often related to the predisposing disease rather than direct cryptococcal-induced mortality and this may partially explain this observation [Although ervation ,39. See After inhaled Cryptococcus cells are phagocytosed by alveolar macrophages, they alter the macrophage transcriptome, preventing significant acidification, calcium efflux and protease activity, and thereby allowing intracellular pathogen proliferation .C. gattii can modulate macrophage polarisation to M2, thereby evading immune recognition and clearance [C. gattii impacts signalling, cell differentiation and regulation of immune system processes, while C. neoformans modulates the cellular response to stimulus, response to DNA damage and cell death [Classically activated M1 macrophages that result from the usual Th1 cytokine immune profiles are essential for clearing Cryptococcus, while alternatively activated M2 macrophages resulting from Th2 cytokine stimulation are associated with a higher burden of disease ,53. C. glearance ,52,53. Tlearance . C. gattll death .Deficiencies in alveolar macrophage functions, including phagocytosis and pattern recognition receptors, result in an intracellular proliferation of Cryptococcus. Subsequent abnormalities in cytokine and protein signalling pathways then initiate a suboptimal or potentially pathogenic immune response, depending on where the deficiency lies . AdvanceEndogenous interferon (IFN)-gamma production is associated with protection against Cryptococcus disease, leading to increased phagocytosis and fungicidal activity of phagocytes. Although exogneous IFN-gamma is sometimes useful as a therapy for refractory IRIS , as discC. gattii VGI and VGII genotypes cause most infections in immunocompetent hosts, while VGIII and VGIV are mainly isolated from immunocompromised hosts. Genotype VGII is the most heat-resistant of the known strains, especially at 37 °C. Different subtypes have different gene expressions identified in vitro, which correlate with their observed virulence clinically. Notably, the outbreak strain VGIIa, in a whole genome sequencing study, demonstrated genetic transformation and mitotic microevolution from 12 missense mutations and one shift mutation. Hypervirulent strains of C. gattii, but not C. neoformans, demonstrate enhanced mitochondrial tubularisation, which positively correlates with intracellular proliferative capacity within macrophages, a possible species-specific virulence mechanism [echanism .C. gattii compared with C. neoformans, perhaps reflecting their different environmental niches and contributing to different clinical manifestations [Both species elicit a robust host immune response. However, murine studies note a considerably different species-dependent host transcriptomic profile . There istations .C. gattii [C. gattii has an additional xylose residue compared to C. neoformans [Another difference is related to the cryptococcal capsule. The cryptococcal capsular polysaccharides, glucuronoxylomannan (GXM) and galactoxylomannan, simultaneously evoke an immune response, enhancing pathogen virulence and allowing evasion of immune recognition by coating antigens on . gattii . The GXMoformans .C. neoformans and C. gattii, hypothetically, are subjected to different herbicidal and environmental pressures, which may differentially alter capsule size and melanin production.Two structural factors associated with increased virulence, the larger size of the dynamic capsule and increased melanin production protecting against reactive oxygen species, are impacted by environmental conditions, with the former shown to be altered by some common herbicides . The difC. gattii seems to have a greater propensity to form titan cells [Capsule size correlates with virulence, although not case-fatalit . Notablyan cells . Titan can cells .C. gattii melanise more slowly than C. neoformans [oformans . Melaninoformans , and theC. gattii have a greater ability to form biofilms in vitro, which may also contribute to differences in disease phenotype between the species [Some strains of  species . Along w species ,65,66.C. gattii genotypes, phenotypes, virulence and regulatory mechanisms is recommended for those interested in further reading on this topic [A recent in-depth review summarising is topic .C. gattii infection, and recommendations are based on expert opinion as, to date, no prospective randomized controlled treatment trials have been conducted for C. gattii infection. The rarity of C. gattii infection presents a significant challenge to conducting such trials. For severe infection, many clinicians favour a prolonged induction therapy with liposomal amphotericin B and 5-flucytosine (4–6 weeks) followed by consolidation therapy for 12–18 months, and this is supported by an Australian case series [C. gattii infections in the last decade—more research is needed to optimise this aspect of care.Six international consensus guidelines have been released in the past decade covering cryptococcal infections ,70,71,72C. gattii and C. neoformans. Olorofim has no activity against either. Rezafungin, as consistent with data for the echinocandin class of antifungal, is not active against C. neoformans and is unlikely to be effective for C. gattii . There were no data for ibrexafungerp. Not included in that review was oteseconazole, a novel tetrazole, which shows activity against C. neoformans, though no data are available for C. gattii [C. neoformans but not C. gattii.A comprehensive review of the antifungal drug pipeline in 2021  reported. gattii ,75. A le. gattii ,77. SeveC. neoformans patients.Given the relative dearth of agents in the antifungal pipeline and the ongoing high mortality and morbidity rates with existing antifungal therapy, researchers have enthusiastically pursued adjunctive therapies. Despite their theoretical promise, trials have returned disappointing results. However, it must be highlighted that the following studies for “cryptococcal meningitis” were not species-specific and mainly recruited ClinicalTrials.gov as of 26 November 2022.Both pathogen and host play roles in tissue damage, so immunomodulation is a natural target for adjunctive therapies. Under this category, both IFN-gamma and dexamethasone have been subject to clinical trials in HIV co-infected patients. In 2004, a double-blind placebo-controlled trial (n = 70) of adjunctive IFN-gamma Ib (100 or 200 μg thrice weekly for ten weeks) showed a non-significant trend towards improved CSF clearance of cryptococci . HoweverC. gattii) and animal models. In 2016, results of a double-blind, randomised placebo-controlled trial  which recruited patients in Vietnam, Thailand, Indonesia, Uganda, and Malawi, were released [C. gattii infection.Dexamethasone was considered a promising therapy for HIV-associated CM based on mortality benefits in tuberculous meningitis and confirmed bacterial meningitis , and supreleased . The trireleased . Dexametreleased . NotablyC. gattii infections and patients with mass CNS lesions [Unfortunately, there is insufficient evidence to inform clinicians about the harms or benefits of steroids in HIV-uninfected cryptococcal meningitis patients. These patients have a very different baseline immune response to HIV-co-infected patients, so responses are likely to differ. Case series have described benefits, especially in  lesions ,83, but  lesions .Other agents have been identified as promising non-immunomodulating adjuncts, although again, results have been disappointing. Between 2018–2020 three trials were published reporting on the efficacy of the selective serotonin reuptake inhibitor sertraline in cryptococcosis ,86,87. AC. gattii and dendritic cell-based vaccines are under investigation as vaccine antigens [C. gattii and C. neoformans regardless of whether the cells are titan or not, but with a more pronounced affinity for the yeast form and reduced the size and number of pulmonary titan cells in cryptococcus infected mice [Work on cryptococcal vaccinations has been undertaken since the 1950s, with many different antigens and delivery systems protecting against infection or attenuation of disease in animal studies. More recently, acapsular strains of antigens ,89,90. Aantigens . Althougted mice ,92.Although there are multiple strategies to diagnose cryptococcosis, with and without fungal culture, diagnosis can be challenging. Delays in treatment because of missed early diagnoses or incorrect diagnoses, lead to worse clinical outcomes .C. gattii turns the culture medium blue, whereas C. neoformans does not change the colour of the medium [Traditionally, fungal culture has been used to diagnose cryptococcosis see . Whilst e medium .In terms of microscopy, Cryptococcus can be seen in body fluid with India ink see  examinatX-ray, computerised tomography (CT) scans and magnetic resonance images (MRI) of the lungs (pulmonary cryptococcosis), brain , and other parts of the body are valuable adjunctive tools for diagnosing cryptococcosis and especially the extent of disease, but radiography results alone are unlikely to be diagnostic ,97,98.C. gattii infections, including infections caused by C. gattii and C. neoformans hybrids [Serological diagnostic tests are used to detect cryptococcal capsular polysaccharide in serum and CSF by Latex agglutination test (LATs), enzyme-linked immunoassays (ELISA). These tests have an overall sensitivity and specificity of 93–100% and 93–98%, respectively [ hybrids .C. gattii infections which may be missed by other serological tests.The introduction of cryptococcal antigen lateral flow assays (CrAg-LFA) marked a major revolution in the diagnosis of cryptococcal infections . CrAG-LFC. neoformans and C. gattii. Recently, a real-time PCR assay targeting the multicopy mitochondrial cytochrome b (cyt b) gene to detect C. neoformans and C. gattii has been developed [C. neoformans and C. gattii. The overall reported assay sensitivity was 96.4%, and the specificity was 100%, and it can diagnose cryptococcosis in patients within four hours [Although molecular assays, such as polymerase chain reactions (PCRs), are potentially a more rapid diagnostic method than culture and antigen testing, such assays are not routienly required. When in use, commercial PCR-based assays that target Cryptococcus cannot distinguish between eveloped . The assur hours . The tarC. neoformans and C. gattii in clinical CSF specimens [C. neoformans per reaction within 10 min and be highly specific to Cryptococcus species. The assay sensitivity was 95.2%, and the specificity was 95.8% [C. neoformans or C. gattii to detect cryptococcosis in CSF [C. neoformans and C. gattii, and may not be able to detect cases where CSF is clear of infection.The novel lateral flow strips combined with recombinase polymerase amplification (LF-RPA) assays were developed to detect the specific DNA sequences of pecimens ,104. Theas 95.8% . MeanwhiC. gattii and C. neoformans [Other recent advances include identification systems such as MALDI-TOF MS. This is a rapid identification tool that can identify both oformans . It offeoformans .C. neoformans and C. gattii [C. neoformans and C. gattii in clinical samples directly. SERS is rapid and nondestructive and has relatively low equipment cost. Briefly, it was shown that AgNPs-self-assembled on the fungal cell wall surface via electrostatic aggregation, leading to enhanced SERS signals that were better than the standard substarte negatively charged AgNPs. The SERS spectra could then be used as a sample database in the multivariate analysis via orthogonal partial least-squares discriminant analysis. The SERS detection method can accurately (was shown to be 100%) distinguish between C. neoformans and C. gattii using principal component analysis. SERS seems to be a breakthrough, though further evaluation will be required before it can be introduced into routine clinical practice.Surface-enhanced Raman scattering (SERS) and spectral analysis offer an additional potential diagnostic tool for . gattii . This noC. gattii and C. neoformans at the individual patient level given their differences in patient predisposition, disease phenotype, and treatment approaches. Treatment trials should include patients infected with both strains and, where possible, run subgroup analyses to identify any differences.In conclusion, it is valuable to distinguish between C. gattii and C. neoformans. Ongoing basic science research is vital to identify potential new targets for both organisms.At the population/public health level, molecular characterization of the strains circulating in specific geographies can provide valuable information on virulence and impacts on at-risk groups. Although there is currently no evidence of differences in MICs impacting treatment outcome it is important that in vitro and in vivo studies of new antifungals include both Ensuring that diagnostic tools are effective against both strains is also crucial. Further research comparing IRIS manifestations and therapies between the two species would be valuable in reducing morbidity and mortality.C. neoformans as the causative pathogen. Consequently, our understanding of cryptococcosis in other settings remains poor, and we struggle to know how much can be directly translated. These gaps can only be filled by establishing large international collaborative networks designed to describe the protean manifestations of cryptococcosis in well-established and emerging niche host groups. These large networks would be fertile ground for investigating novel antifungal or adjunctive therapies, including proper assessment of pharmacokinetic-pharmacodynamic and drug-drug interactions in disparate groups.The vast majority of high-grade evidence on the management of cryptococcosis comes from HIV-associated cryptococcal meningitis trials, which are increasingly conducted in low- and middle-income countries with the highest disease burden and a predominance of