Global trade of feed ingredients that may be contaminated with significant concentrations of swine viruses is a concern for the potential transmission of swine diseases because viable virus particles can survive in feed ingredients and complete feed for several weeks or months. No global swine virus surveillance and monitoring system exists to determine the possible presence and concentrations of swine viruses in feed ingredients. Biosecurity protocols based on hazard analysis and risk-based preventive controls must be developed and implemented in feed ingredient supply chains to prevent virus contamination. In addition, mitigation strategies including the use of extended storage time, thermal and irradiation processing, and certain feed additives have been shown to provide partial virus inactivation in contaminated ingredients and complete feeds under specific conditions. However, analytical methods capable of accurately determining viable virus concentrations that can lead to infection are lacking and need to be developed. Effective feed mill decontamination strategies are also needed for various swine viruses. Several functional ingredients and nutrients such as spray-dried animal plasma, medium-chain fatty acids, and soy isoflavones have antiviral properties and have been shown to alleviate adverse health of pigs undergoing a viral disease challenge when included in diets.No system nor standardized analytical procedures at commercial laboratories exist to facilitate and accurately measure potential viable virus contamination in feed ingredients and complete feeds globally. As a result, there is high uncertainty of the extent of swine virus contamination in global feed supply chains. Many knowledge gaps need to be addressed to improve our ability to prevent virus contamination and transmission in swine feed. This review summarizes the current state of knowledge involving: (1) the need for biosecurity protocols to identify production, processing, storage, and transportation conditions that may cause virus contamination of feed ingredients and complete feed; (2) challenges of measuring virus inactivation; (3) virus survival in feed ingredients during transportation and storage; (4) minimum infectious doses; (5) differences between using a food safety objective versus a performance objective as potential approaches for risk assessment in swine feed; (6) swine virus inactivation from thermal and irradiation processes, and chemical mitigants in feed ingredients and complete feed; (7) efficacy of virus decontamination strategies in feed mills; (8) benefits of functional ingredients, nutrients, and commercial feed additives in pig diets during a viral health challenge; and (9) considerations for improved risk assessment models of virus contamination in feed supply chains. Concerns about the transboundary transmission of swine viruses through international trade and travel  have ledThe major swine viruses of concern for potential transmission through global feed supply chains are PEDV, African swine fever virus (ASFV), classical swine fever virus (CSFV), porcine respiratory and reproductive syndrome virus (PRRSV), Seneca Valley A virus (SVV-A), and foot and mouth disease virus (FMDV). Although a few reports have provided evidence that contamination of some viruses such as ASFV , CSFV 1, and SVVSalmonella enterica, PEDV, and ASFV. However, accurate interpretation of results from this study is difficult because no uncertainty estimates nor detailed assumptions used to make these determinations were provided.Because of the high uncertainty, mathematical models have been developed to evaluate the likelihood of virus transmission through feed. Galvis et al.  evaluateSeveral laboratory-based inoculation studies have shown that most swine viruses of concern can survive in some feed ingredients for several weeks or months ,25,26,27Identifying conditions during production, processing, transportation, and storage that can lead to virus contamination of feed ingredients;Determining the likelihood of swine virus contamination in feed;Understanding the chemical and physical characteristics of feed ingredients that allow various types of viruses to survive;Understanding the unique characteristics of various types of viruses that enable their survival and make them vulnerable to inactivation and loss of infectivity;Developing and validating highly sensitive and specific assays that accurately quantify viable and infectious virus particles for various viruses in different types of feed ingredients;Identifying time and temperature conditions that effectively inactivate viruses without degrading the nutritional value of ingredients;Identifying chemical mitigants that effectively inactivate viruses without degrading the nutritional value or safety of ingredients;Determining effective practices for decontaminating feed mills;Determining minimum concentrations of viruses and feeding conditions that prevent disease when pigs consume contaminated feed.Because of the global trade of feed ingredients and subsequent movement of imported ingredients to feed mills and swine farms, feed biosecurity programs to minimize the risk of virus contamination and transmission have emerged as a relatively new component of feed safety and biosecurity protocols. Approaches to risk management of ASFV transmission through imported feed ingredients vary among countries ,29. In tBecause of our inability to accurately and routinely determine the presence, concentration, viability, and infectivity of virus contamination in feed ingredient supply chains, this high uncertainty of potential virus contamination requires development and implementation of biosecurity protocols that focus on specific swine viruses of concern. However, until more strict biosecurity regulations and programs are implemented, effective mitigation strategies are also needed to reduce viral load and viability in feed ingredients suspected of being contaminated. The biosecurity of swine farms is an essential component for preventing introduction and controlling pathogens that cause foreign and endemic disease, and for maintaining high health to optimize productivity. International biosecurity guidelines have been developed that involve minimizing the exposure of animals to external hazards that are potential routes of pathogen transmission . Major rFeed manufacturing facilities are a collection, storage, proportioning, mixing, and processing point for various types of feed ingredients sourced from many geographic regions before finished complete feeds are delivered to multiple farms. Therefore, the biosecurity of feed mills must be a major part of the overall biosecurity program for swine farms to prevent pathogen introduction. Cochrane et al.  describeMechanisms for evaluating the quality, safety, and biosecurity procedures used by suppliers in the production of ingredients, including auditing and verification that protocols are followed;Facility design and maintenance protocols that prevent or reduce the introduction of pathogens;Routine housekeeping procedures that adequately prevent or reduce the introduction of pathogens;Standard operating procedures (SOPs) and surveillance programs for biosecurity that include ingredient sourcing, receiving, and storage;Biosecurity and personal hygiene protocols for visitors, employees, and drivers to control access to the facility;Manufacturing practices that are effective for maintaining the biosecurity protocols of the facility;Biosecure transportation of finished feed using sealed containers and disinfection practices.Feed manufacturers are responsible for the biosecurity of the feed supply chain, which begins with sourcing, receiving, and processing feed ingredients used to manufacture complete feeds until the delivery of finished feed to swine farms . The Amehttps://www.fda.gov/food/food-safety-modernization-act-fsma/fsma-final-rule-sanitary-transportation-human-and-animal-food) (accessed 26 March 2023). Biosecurity protocols for sanitary transport of imported ingredients should include HARPC plans to reduce the risk of adulteration or cross-contamination of viruses. Key components of sanitary transport protocols include:Documentation verifying that the manufacturing and storage facilities in the country of origin have been decontaminated;One-way driveways for dirty vehicles and containers should be used to separate potentially contaminated vehicles and containers from those that are empty, clean, and disinfected using approved and effective disinfectants;Washing and disinfection facilities should be provided, and their use required for all trucks and equipment used for feed transport;After disinfection, transport vessels should be loaded and sealed at the manufacturing facility before transport to the destination;After ingredients are loaded and sealed, trucks should enter the delivery destination through a “clean” driveway;After unloading, transport time and temperatures conditions should be recorded and considered when estimating required holding times during storage at the destination;Upon arrival at the destination, only trucks that are empty, clean, and disinfected should be used to transport bulk ingredients for quarantine in a heated temporary warehouse;For bagged ingredients, new or properly cleaned and disinfected pallets should be used;Documentation of storage conditions and holding times for each lot of each feed ingredient should be provided to end users.Sanitary transport is commonly overlooked in biosecurity protocols. However, trucks, driver shoes, bags, and totes have been identified as the primary route of pathogen transmission associated with feed in several studies ,13,14,17Upon completion of a comprehensive feed mill biosecurity plan, all new procedures must be correctly implemented to reduce the likelihood of pathogen introduction. Therefore, employee training must be provided so that they can demonstrate an understanding of each risk factor being controlled and that they are capable of following procedures and protocols to minimize each risk. Unannounced internal audits are useful to ensure compliance with existing procedures and to identify aspects of protocols where more employee training is needed. Biosecurity plans should be re-evaluated at least once annually or when a new feed ingredient source is acquired at the feed manufacturing facility. External third-party audits, review, and consultation from qualified feed mill biosecurity experts are also useful practices for identifying potential hazards that may have been overlooked when initial protocols were developed.Salmonella, Escherichia coli, and Clostridium perfringens contamination in feed samples have been routinely used for many decades [50 [50) [Accurate and repeatable analytical assays for routine evaluation and monitoring of common bacterial pathogens including  decades . Virus-sades [50  and hema[50 [50)  and in v[50 [50) . Unfortu3 TCID50/g or 105 TCID50/g PEDV and collected samples using individual probes or composite sampling. These researchers reported that composite samples were more sensitive to virus RNA than probes in bulk soybean meal and suggested a minimum of 10 subsamples be collected for creating a composite sample for analysis. Elijah et al. [Accurate determination of virus concentrations in feed ingredients begins with collecting representative samples. However, viruses in contaminated feed may not be uniformly distributed and may be present in low concentrations. No sampling methods have been validated for use in collecting representative feed samples for virus analysis. Jones et al.  inoculath et al.  evaluateh et al.  and suggThere are also numerous challenges with using existing analytical assays for the accurate detection of viable virus particles in feed ingredients that can lead to infection, especially for ASFV . MeasuriTargeted virus diagnostic methods must have high specificity (accurately identify negative results) and high sensitivity (accurately identify positive results) to accurately quantify the amount of viable virus particles capable of causing infection if ingested by pigs . Results50/mL) is another common assay used to calculate virus concentrations by incubating a red blood cell suspension with an infected cell culture to measure 50% of the replicates, showing the amount of virus hemadsorption per milliliter of blood [50) per gram of sample, which measures the amount of virus capable of infecting 50% of cell culture replicates, but it does not directly infer infectivity in pigs. More recently, surrogate assays have been developed for some swine viruses in research applications because using the actual virus of interest, such as ASFV [For some viruses, PCR methodologies have been modified to create viability PCR assays that distinguish between viable and free DNA in feed samples . Howeverof blood . Howeverof blood . The mos as ASFV , CSFV, o as ASFV , is rest as ASFV  to confi as ASFV . 3 reduction from the initial virus concentration and should not be interpreted as 0.1% virus particles remaining in the sample. Therefore, depending on the initial virus concentration, a 99.9% or 3-log reduction in virus from thermal or chemical mitigation treatments may exceed the minimum infectious dose for a contaminated feed and potentially result in an infection. In addition, virus inactivation kinetics curves usually fit non-linear patterns with shoulders or tails and do not follow first-order kinetics (log-linear). Half-life  data for virus inactivation reported in some studies does not provide an accurate estimate of virus inactivation in a feed ingredient because it is based on the assumption of a linear relationship between the logarithmic decrease in virus concentration and time of mitigant exposure. However, using inactivation data to calculate D-values  and z-values  are useful to make comparisons of virus inactivation kinetics across studies and predict outcomes not previously determined experimentally. Unfortunately, most studies have not provided adequate data suitable for calculating D- and z-values to more accurately determine virus inactivation kinetics in feed ingredients [In addition to understanding the specific state of viruses being measured by various assays, accurate interpretation of results from virus inactivation studies is also essential. The term “complete inactivation” of viruses should be avoided because it infers zero risk of infection in pigs consuming feed that was originally contaminated, which is not possible . Althougredients . In summSeveral studies have evaluated virus survival in feed ingredients under various types of transport conditions. The initial study was conducted by Dee et al.  and inclSimulations of long-distance truck transport of virus-inoculated feed ingredients and complete feed in the U.S. have also been evaluated. Dee et al.  conducteSeveral studies have evaluated the use of extended storage time as a mitigation strategy to determine the rate and extent of inactivation of various swine viruses in different feed ingredients during various time and temperature exposures, and the results are summarized in Although extended storage times have been shown to be a simple and effective way of reducing virus concentrations in feed ingredients and complete feeds if they are contaminated, there are several unintended consequences that must also be considered. Storage facilities for feed ingredients represent a significant cost for feed handling and manufacturing facilities. As a result, frequent inventory turnover is required to minimize the cost of ingredient procurement and feed manufacturing. Furthermore, depending on the time, temperature, and relative humidity conditions of various types of feed storage and the physical and chemical characteristics  of ingredients, significant feed safety concerns and loss in the nutritional value of ingredients can occur. High temperature, humidity, and moisture conditions cause bacteria growth and mold and mycotoxin production during storage that can be detrimental to animal health and performance. These same conditions can also lead to significant losses of nutritional quality and value through reduced protein and amino acid digestibility, production of secondary lipid oxidation products, and loss of vitamin potency. Therefore, maintaining a balance between minimal storage time to reduce cost and preserve nutritional value and allowing adequate time for significant virus inactivation must be considered when using this mitigation strategy to inactivate swine viruses in contaminated feed ingredients.https://www.agriculture.gov.au/import/goods/plant-products/stockfeed-supplements) (accessed 26 March 2023) and the European Union  (accessed on 26 March 2023) also provide guidelines for assessing the risk of ASFV in imported feed ingredients but do not specifically require a standard 30-day storage period for suspect ingredients.Dee et al.  indicateThe number of studies assessing the survival of several of these important swine viruses in numerous common feed ingredients used in swine diets under different time and temperature conditions are limited. No studies have been conducted to evaluate CSFV survival during storage under controlled time and temperature conditions. Estimates for FMDV, porcine delta corona virus (PDCoV), transmissible gastroenteritis virus (TGEV), and PRRSV survival have each been determined in only one study, and the ingredients evaluated were limited to only soybean meal for PRRSV and soybean meal, DDGS, and complete feed for FMDV. Two studies have evaluated ASFV survival in four ingredients and an additional two studies have evaluated SVV-A survival in four ingredients. Although these are critically important studies to provide initial guidance on recommended storage times for virus inactivation of ingredients suspected of being contaminated, the data available from these studies is insufficient for supporting the 30-day extended storage time recommendation proposed by Dee et al. . All of To better understand the significance of the inconsistencies reported for extended storage time studies, consider the different methods, ingredients, and interpretation of results between the two studies evaluating ASFV in Feeding frequency of pigs used in bioassays and virus strain were additional factors beyond time, temperature, and assay methods that affected results for FMDV survival in soybean meal, DDGS, and complete feed during a 37-day storage period . The lasExtrapolating minimum storage times for virus inactivation is difficult if storage temperatures are below those commonly found in warm climates. For example, one extended storage study was conducted under conditions of extremely low and variable storage temperatures  to evaluate PEDV survival in 18 feed ingredients during a 30-day storage period . BecauseCoronaviridae family, of which PEDV and TGEV are classified in the Alphacorona virus genus, and PDCoV is in the Deltacorona virus genus [Extrapolating virus survival and inactivation data for a specific virus of interest from data derived from other virus types has been done, but it is not advised because of the uniqueness of each virus and the complexities of their behavior in various feed matrices. For example, PDEV, PDCoV, and TGEV are in the us genus . These cus genus . Howeverus genus  showed tOne cannot extrapolate virus inactivation results for individual feed ingredients or complete feed from studies that used non-feed matrices or cell cultures. Knight et al.  summariz5 TCID50 of SVV-A and the same concentration of PRRSV were added to feed ingredients. Results showed that only the storage temperature of 23.9 °C was effective in achieving no infectivity after 30 days. In contrast, Caserta et al. [5 TCID50 of SVV-A and showed that virus inactivation in L-lysine HCl and vitamin D occurred within 1 day at 15 °C and 30 °C compared with soybean meal and DDGS, which survived until 35 days at 15 °C and until 21 and 14 days, respectively, at 30 °C. Although Caserta et al. [Dee et al.  evaluatea et al.  inoculata et al.  did not Although soybean meal appears to be most protective for swine virus survival, it has also been the most studied of all ingredients. Other grains, grain by-products, and oilseed meals must also be evaluated for their ability to protect various swine viruses if they become contaminated because they are added to diets at much greater inclusion rates than vitamins and synthetic amino acids, and subsequently could contribute a greater virus dose for pigs to consume. However, results from several studies evaluating the survival of several viruses in soybean meal have shown that more than 30 days storage, even at relatively low temperatures, is necessary to achieve significant virus inactivation. The likelihood of a virus-contaminated ingredient causing infection is not only dependent on the initial virus concentration used to inoculate feed ingredients, and the subsequent extent of virus inactivation and loss of infectivity that may occur during storage, but also on the frequency of consumption of contaminated feed  ,61 that Structural and chemical characteristics of various feed ingredients likely play a role in the differences in survival of various viruses among different feed ingredients, but these factors have not been studied. The moisture content of feed ingredients and complete feeds is relatively low (<12%), but Trudeau et al.  reported4 for all other major swine viruses, which suggests that achieving a 3-log reduction in infectious virus concentration from an initially high theoretical contamination level of 106 in complete feed would be below MID for all viruses except for SVV-A in market-age pigs. However, all of these MID estimates are based on observations from a relatively small number of pigs used in these studies and would likely decrease when estimated using a greater number of animals in a population of pigs.Estimates for minimum infectious doses (MID) of several swine viruses have been determined through consumption of inoculated feed or direct oral inoculation in pigs . Virus sSalmonella in feed can still cause an infection when fed [7.0 TCID50 of FMDV three times, all pigs (4 of 4) were infected after two days. Likewise, after consuming 107.2 TCDI50 of FMDV only one time, all pigs (4 of 4) were infected [The minimum infectious dose cannot be interpreted as a concentration in which a product, if contaminated, is considered safe, or the safe concentration from which no infection will occur. The MID in the experiments presented in when fed . This diinfected . These rThe minimum infectious dose is different from other estimates of food and feed safety such as the food safety objective (FSO) and performance objective (PO) . These tIn addition to extended storage times, thermal processing can be an effective method of inactivating bacteria, viruses, and parasites depending on the temperature and duration . Heat isMost studies conducted with feed ingredients and complete feed have evaluated thermal processing on PEDV inactivation. A summary of the effects of various time and temperature conditions used during various types of production processes of feed ingredients and complete feed is shown in 50/mL reduction [Several studies have shown that the use of ultraviolet irradiation is an effective additional biosecurity step to further inactivate several enveloped  and non-enveloped swine viruses during the spray drying process of liquid porcine plasma . In geneeduction . Additional studies have been conducted to evaluate the effectiveness of the spray drying process used for animal plasma ,77,79,81Salmonella in poultry and swine feed, it is not approved for use in controlling swine viruses in the U.S. and numerous other countries. Various individual MCFAs and MCFA blends have also been extensively evaluated for their potential viral mitigation effects. Unlike FMPA, MCFAs such as C6:0 (caproic acid), C8:0 (caprylic acid), C10:0 (capric acid), and C:12:0 (lauric acid) are naturally found in triglycerides present in common fats and oils used in animal feeds, and their use is generally not restricted in commercial swine feeds. A few commercial products that have been evaluated as chemical mitigants in virus-contaminated swine feed contain certain short-chain or long-chain fatty acids, but their potential viricidal effects are questionable. Glycerol monolaurate has been shown to have more potent viricidal effects than MCFA for ASFV [Limited studies have been conducted to evaluate various types of feed additives for their effectiveness as chemical mitigants for inactivating ASFV ,86, FMDVfor ASFV . In addifor ASFV , PDCoV [for ASFV , PRRSV afor ASFV , and PEDfor ASFV ,88,97. Ofor ASFV  and PEDVfor ASFV  inactivaAmong all swine viruses evaluated, ASFV is the most difficult to inactivate because of its high thermal tolerance . FortunaPathogen contamination can occur on feed and non-feed contact surfaces in feed mills if contaminated feed ingredients are introduced, despite the use of well-designed and well-implemented feed mill biosecurity protocols ,98. BecaBiosecurity and mitigation strategies to reduce the risk of bacterial and viral pathogen contamination in feed mills have been evaluated and summarized based on a limited number of studies ,99. FeedOne of the simplest methods for decontaminating virus-contaminated feed and feed ingredients is to store potentially contaminated batches for an extended period of time in a heated warehouse or feed mill. Several government protocols have been developed and implemented in Canada , the EurMechanical reduction of PEDV concentration in experimentally contaminated feed manufacturing facilities has been evaluated using batch sequencing  and flusBecause all viruses have some sensitivity to heat exposure, the heat provided during the conditioning and pelleting process in feed mills can be effective in reducing or eliminating the infectivity of swine viruses. Cochrane et al.  conducteThe effectiveness of chemical cleaning and sanitizing feed mill equipment and surfaces to reduce PEDV concentration has also been evaluated. Huss et al.  applied Several plant extracts contain compounds with antiviral properties, including flavonoids, alkaloids, phenolic acids, terpenes, coumarins, lignans, and proteins . Of thesIsoflavones are flavonoid compounds that have potent antiviral properties against a wide variety of viruses, including enveloped and nonenveloped, single-stranded and double stranded, and RNA and DNA viruses . SoybeanOf all swine viruses, PRRSV is the only virus that has received research attention relative to the dietary benefits of soy isoflavones. Several studies have shown consistent growth performance and health benefits from feeding diets with high amounts of soybean meal to pigs infected with PRRSV. Results from initial studies showed that dietary daidzein provided less improvement in the growth of weaned pigs during a PRRSV challenge  than gen4 or 105 TCID50, and fed the contaminated feed for 14 consecutive days to determine if it would cause infection in naïve weaned pigs in two separate experiments. None of the pigs in either experiment became infected, indicating that either the minimum infective dose of ASFV is greater than 105.0 log TCID50/pig or that liquid porcine plasma has significant functional properties that may reduce the infectious capability of ASFV. Additional evidence of the functional benefits of feeding spray-dried animal plasma to weaned pigs was observed in a study conducted by Crenshaw et al. [Spray-dried animal plasma contains many functional compounds, including immunoglobulins, albumin, fibrogen, lipids, growth factors, biologically active peptides, transferrin, enzymes, and hormones , that plw et al. , which sFeeding spray-dried animal plasma to weaned pigs also appears to enhance immune response to vaccines. Weaned pigs fed a starter diet containing SDPP and vaccinated for porcine circovirus type 2 and Mycoplasma hyopneumoniae supported the best long-term benefits in survival to market and carcass weight . More reMonoglycerides and MCFA have become one of the most important types of antiviral feed additives for use in swine diets, and their molecular properties and biological functions have been reviewed and summarized . Medium-Hanczakowska  summarizMost of the research conducted to study the antiviral effects of flavonoids, alkaloids, phenolic acids, terpenes, and coumarins in plant extracts has involved either human coronaviruses or influenza viruses . PositivEffective treatments for pigs infected with ASFV are desperately needed because no effective and safe vaccines are available to prevent ASFV infection in pigs. Studies have shown that nucleoside analogues, interferons, specific flavonoids, a limited number of antibiotics, and small interfering RNA molecules inhibit ASFV replication by either acting directly as antiviral compounds or specifically providing certain antiviral effects in the host . SeveralFluoroquinolones are a class of antibiotics that are approved for use in treating certain types of bacterial infections but have also been shown to exhibit potent antiviral properties. These antibiotics trap DNA gyrases and topoisomerase IV on DNA and promote the formation of drug enzyme-DNA cleavage complexes that cause disruption of DNA replication, leading to mechanisms resulting in cell death . ModificLimited studies have evaluated the effects of various salts on swine virus inactivation. One study involved experimentally infecting pigs with CSFV and ASFV, euthanizing them during the acute phase of disease when viremia was greatest, and collecting small and large intestine samples for incubation with either sodium chloride or a salt mixture  at various temperatures up to 20 °C for multiple times up to 60 days . Both soMetals such as copper and zinc possess several properties including redox, photocatalytic, and structural stability, along with antibacterial and antiviral properties , that suThe goal of feed supply chain biosecurity programs is to deliver complete feeds to swine farms that are devoid of disease-causing pathogens. However, if viral pathogen contamination is suspected in complete feed delivered at the farm level, the addition of several commercially available feed additives to swine diets may improve the health and growth performance of pigs fed contaminated feed and undergoing a disease challenge. Many antiviral commercial feed additives containing various combinations of MCFA blends, glycerol monolaurate, organic acids, essential oils, and various other compounds have been developed, approved for use, and commercially available in some countries.Fifteen commercially available feed additives were evaluated when added to nursery feed contaminated with PRRSV, SVV-A, and PEDV to determine their effectiveness in improving the health and growth performance of pigs . A serie8.3 TCID50 FMDV A24 (greater than the previously determined minimum infectious dose) to feed with or without SalCurb or Guardian feed additives 24 h prior to feeding and observed no clinical signs or positive antemortem samples for pigs fed either feed additive treatment, except for one pig fed Guardian that was considered subclinically infected. Two of the feed additives evaluated in this study  were alsBeyond the results reported in these studies, it is unknown if these additives are effective in improving health and growth rate in swine diets contaminated with ASFV or other swine viruses. However, these results suggest that several commercially available feed additives may be effective as a last defense against a biosecurity breach to minimize adverse health effects from PRRSV-, SVV-A-, and PEDV-contaminated swine feed.Quantitative risk assessment of virus transmission through various feed ingredient supply chains is greatly needed because of high uncertainty due to the lack of a global monitoring and surveillance system. Unfortunately, most publications in the literature do not provide sufficient details and data to enable the development of quantitative risk assessment models. Many experiments evaluate only a single temperature, sampling time, or measure of virus inactivation rather than evaluating a comprehensive set of conditions. Furthermore, very few studies have reported D-values or z-values for virus inactivation kinetics that allow for comparison of results among studies. Accurate estimates for kinetic parameters of virus inactivation require multiple time and temperature conditions. Typically, virus inactivation curves follow non-linear patterns, which are best modelled with at least 4–5 observations distributed along the expected range in temperatures and sampling times in virus inactivation models. A limited number of replications per timepoint or temperature is another common problem with the data provided in the published literature. Many researchers fail to recognize the appropriate experimental unit and the number of experimental units associated with the error term measurement of the virus inactivation. Pilot experiments can be a useful approach for collecting preliminary data on the variability of conditions associated with virus inactivation to determine optimal subsequent experimental design. In the predictive modeling of pathogen inactivation, there are sources of uncertainty and variation in observed predictions that are introduced due to unknown effects of independent factors. Another source of variation is actual variability in the process input range. Because this source of variation is known, it should be estimated using sensitivity analyses. In summary, researchers are encouraged to consider these key deficiencies when reporting virus inactivation data from various mitigation strategies in feed ingredients in future studies to enable subsequent quantitative risk assessment determinations. Compared with other virus transmission routes, feed ingredients and complete feed appear to be less likely contributors toward disease transmission, but because there is no monitoring and surveillance system, there is high uncertainty of the extent of swine virus contamination in global feed supply chains. Biosecurity protocols need to be developed and implemented to improve our ability to prevent virus contamination and transmission through the production, processing, storage, and transportation of swine feed. Key components of feed biosecurity protocols should also include effective mitigation practices such as extended storage times, thermal and irradiation processing, and chemical mitigants to provide inactivation of viable swine viruses if they are present. Several types of functional feed ingredients, nutrients, and feed additives that have antiviral properties need to be further evaluated for their ability to inactivate swine viruses of concern in various types of feed ingredients. Unfortunately, there are numerous challenges that must be overcome to improve our understanding and ability to accurately predict whether feed contaminated with swine viruses is capable of causing an infection, including limitations of current analytical methods for measuring virus inactivation, viability, and infectivity in feed. In addition, the use of the food safety objective and performance objective need to be developed for risk assessment of virus survival in feed ingredients. Improving data quality and quantity when reporting results in scientific publications is needed to provide sufficient detail to allow for developing risk assessment models and calculating D-values and z-values for virus inactivation kinetics that allow for comparison of results among studies.


Stress is a physiological response of the body to stressful life events but may not be when the individual is persistently exposed to the stress trigger, and it negatively affects certain physiological functions, thus triggering psychosomatic diseases. In literature, chronic stress and inadequate coping strategies are found to mediate the risk and development of periodontitis; mechanisms have therefore been proposed to explain the effects of stress on the periodontium. Since stress is a prevalent problem in modern life and given the importance of maintaining oral health, the present literature review aimed to estimate the association between stress and periodontal disease. The research question adopted is the following: “Are psychological stress and periodontal disease related?” The search was conducted in August 2022 and limited to articles in electronic databases from 2017 to 2022 in English, excluding reviews and literature reviews. From the electronic databases, a total of 532 articles were identified and became 306 after reviews and duplicates were removed. An additional bibliographic search was conducted through the same electronic databases, controlled terms and keywords including only systematic reviews, which were previously excluded. Through the bibliography cited in the systematic reviews, an additional 18 articles were identified, with a new total of 324. As a result of reading the title and abstract of these 324 articles, an additional 295 were excluded. Reading the full text of the remaining 29 studies, 2 articles were excluded due to non-adherence to the eligibility criteria. The remaining 27 results were included in our literature review. It has been suggested in the literature that adverse socioeconomic conditions elicit a stress response, which can trigger periodontal inflammation. Most of the 27 articles included in the study confirm and demonstrate a positive association between psychological stress and periodontal disease. Numerous studies have shown the mechanisms through which chronic stress negatively affects periodontal tissues. Therefore, in the light of the results obtained from this review, it is important that oral health professionals, also for general health purposes, consider stress factors among the risk factors of periodontal disease, its severity and decreased efficacy of treatments. It is therefore advisable to act preventively through the interception of chronic stress. Stress is defined as a physical, emotional, or mental response to stressful life events; it is a physiological response of the body but may not be when the individual is persistently exposed to the stress trigger. Additionally, it negatively affects certain physiological functions, thus triggering psychosomatic diseases .Nowadays, the term stress is used with extreme frequency to describe recurring negative experiences related to everything from everyday inconveniences, relationship problems and work pressures to health problems and debilitating phobias.Exposure to stressors by the body results in the triggering of a series of physiological changes. Stress, depending on its duration, can be distinguished as acute or chronic. These responses set in quickly and just as quickly decay, with a return to homeostasis.In the context of periodontal diseases,  , severe There are two different forms of periodontal disease: gingivitis and periodontitis.Host susceptibility to periodontal disease in terms of extent, severity, progression and response to therapy can be modified by external and internal components, which can be classified into modifiable risk factors and non-modifiable risk factors. The factors that are modifiable, as their elimination or control is critical in the management of periodontal disease, are plaque/tartar, overflowing restorations, partial dentures and dental malposition, while systemic factors include excessive alcohol consumption, smoking, stress, medications and certain medical conditions such as poorly controlled diabetes, obesity, osteoporosis, low dietary calcium and vitamin D ,5.Other systemic factors including certain clinical conditions such as unstable diabetes and leukemia, AIDS, Crohn’s disease and genetic factors such as positive family history of periodontal disease cannot be modified, and are therefore defined as non-modifiable ,5.Studies in the literature indicate that chronic stress and inadequate coping strategies may mediate the risk and development of periodontitis; mechanisms have therefore been proposed to explain the effects of stress on the periodontium. Stress would appear to indirectly influence periodontal health by inducing changes in unhealthy coping behaviors such as smoking, excessive alcohol consumption and illicit drug use, improper diet, neglect of oral hygiene and poor compliance with dental care; it would also appear to influence periodontal health through direct biological impact, mediated through alteration of saliva, changes in gingival blood circulation and by influencing the host immune response .The role of the influence of psychosocial disturbances on the periodontium is not new; on the contrary, stress for many decades has been reported as a risk factor for necrotizing ulcerative gingivitis (NUG), a condition known by the term “trench mouth” associated with bacterial infection and characterized by papillary necrosis, pain and gingival bleeding . This asA patient’s mental health status influences dental hygiene to some extent. Poor oral hygiene due to stress can promote plaque accumulation and over time the occurrence of gingivitis and periodontitis .Several articles in the literature state that dental and medical students are subject to higher stresses. The components post-underestimation had a significant increase during undergraduate exams, compared with post-exams. In conclusion, academic stress has a negative effect on plaque levels and gingival status ,10,11.Furthermore, saliva performs numerous functions. Among these, it plays a key role in chewing, swallowing, phonation and maintaining oral health. In the oral cavity, it performs the function of antibacterial, antifungal, antiviral, furthermore it cleanses and lubricates the dental elements and oral mucosa; likewise, it modulates demineralization and possesses a buffering capacity that promotes the maintenance of neutral pH . SalivarSince stress is a prevalent problem in modern life and given the importance of maintaining oral health, the present work aimed to estimate the association between stress and periodontal disease through a literature review investigating the main relations highlighted in the literature regarding this topic.This systematic review was conducted following the criteria of the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) Statement .-Population (P): human subjects with periodontal disease;-Exposure (E): psychological stress assessed by specialized questionnaires or biological biomarkers;-Comparison (C): periodontally healthy subjects not exposed to psychological stress;-Outcome/Results (O): association between psychological stress and the presence of periodontal disease.The PECO  model was used for formulating the scientific question and as guidance of the inclusion and exclusion criteria of this review. This acronym represents the characteristics of the patient (P), the exposure (E), the comparator (C), and the outcome (O) of the eligible question. The research question adopted is as follows: “Are psychological stress and periodontal disease related?”The search was conducted in August 2022 and limited to articles in electronic databases from 2017 to 2022 in English, excluding reviews and literature reviews.Bibliographic research was conducted by two independent operators through the electronic databases—Pubmed, Scopus and Web of Science—using combinations of selected terms and different keywords, depending on the search mode allowed by each electronic database as shown in The research began in July 2022, continued in August and ended on 6 September 2022.Study selection was performed by two independent operators following the process of Identification, Screening, Eligibility and Inclusion of studies.Articles were saved in the Zotero software , where duplicates were removed. A preliminary screening was then performed by two independent operators, which involved reading the titles and abstracts of the articles, in order to remove the studies not relevant to the purpose of this review.The eligibility process was carried out by reviewing and analyzing the full texts for further inclusion or exclusion. Access to the full texts of the articles was obtained through the “Nilde” (Network Interlibrary Document Exchange) system, in collaboration with Sapienza University of Rome.The papers included in the study were randomized controlled trials (RCTs) and con-trolled clinical trials (CCTs), cohort studies, case–control studies and transversal studies.The excluded studies were literature reviews, articles that were not in English, articles whose full text was not available and studies not carried out on humans.The entire selection process was schematized in the PRISMA Flow Diagram .Data collection was carried out by reading the full texts of the included studies. with related and subsequent manual entry into the tables, using the Microsoft Excel spreadsheet ; gender; age group/middle age; inclusion and exclusion criteria; diagnosis of periodontal disease; instruments used to measure stress; and conclusions.The methodological quality of the included studies was performed by two independent practitioners using “The modified JADAD scale” . The modified scale includes nine criteria or items to which scores are assigned. The score for each study ranges from 0  to 8 , where 0 represents the highest risk of bias and 8 represents the lowest risk of bias. Studies with scores of 7 and 8 were classified as low risk, those with scores of 4, 5 and 6 were classified as moderate risk and studies with scores less than or equal to 3 as high risk. Studies scoring less than 4 were considered low quality, studies scoring 4 or more (with a maximum of 6), were considered medium quality and studies scoring more than 6 were considered high quality.The quality of the selected studies was assessed using the modified version of the Newcastle–Ottawa scale for cross-sectional studies by Wells et al. .Study quality was rated on a scale from 0 (high risk of bias) to 8 (low risk of bias). The scale assessed the parameters of sample selection, comparability and outcome/exposure. Studies that showed a summary score greater than the median value were considered to be at low risk of bias. Each parameter was awarded 1 point. Any disagreements among the reviewers in assessing study quality were resolved by consensus or by consulting a third reviewer.To reduce the bias and time spent in the study selection process, a Cohen’s kappa statistic system was used in the process of selecting studies. An iterative process based on the use of this statistic during which the criteria were refined until obtaining almost perfect agreement (k > 0.85). At this point, the two researchers interpret the selection criteria in the same way; therefore, the bias is reduced.From the electronic databases Pubmed (n = 76), Scopus (n = 438) and Web of Science (n = 18), a total of 532 articles were identified, 306 after duplicates were removed. In addition, an additional bibliographic search was conducted through the same electronic databases, controlled terms and keywords including only systematic reviews, which were previously excluded. Through the bibliography of the latter, an additional 18 articles were identified, with a total of 324.As a result of reading the title and abstract of the latter, an additional 295 were excluded. Reading the full text of the remaining 29 studies resulted in the exclusion of 2 articles due to non-adherence to the eligibility criteria. The remaining 27 results were included in the literature review. The process was schematized in the PRISMA Flow Diagram .The characteristics of the included studies are shown in Periodontal disease was diagnosed by radiographic and clinical criteria. The latter were performed through periodontal measurements of several parameters such as clinical at-tachment level (CAL), plaque index (PI), probing depth (PD), bleeding on probing (BOP), plaque control record (PCR), gingival index (GI), tooth mobility (DM), papillary bleeding index (PBI), periodontal surface inflamed area (PISA), oral polymorphonuclear leukocytes (OPMN), oral inflammation (OIL), oral hygiene index (OHI), simplified oral hygiene index (OHI-S), community periodontal index (CPI), papillary, marginal and adherent gingival index (PMA), and gingival recession (REC). Stress was measured by administering several questionnaires, among them the Depression, Anxiety and Stress Scales (DAS), Perceived Stress Scale (PSS), Hospital Anxiety and Depression Scale (HADS), Percived Stress Questionnaire (PSQ), State and Trait Anxiety Index (STAI), Symptom Checklist 90 (SCL-90), General Health Questionnaire (GHQ-30), Patient Health Questionnaire 9 (PHQ-9), Beck De-pression Inventory (BDI), Scale for Assessing Academic Stress (SAAS), Toulouse Coping Scale (TCS), and Self-Report Psychopathy Scales (SRP). Salivary and serum samples were also taken for the assessment of cortisol, IgA, ghrelin, chromogranin-A, salivary al-pha-Amylase, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intes-tinal peptide (VIP), neuropeptide Y (NPY), Adrenomedullin (ADM).To assess the quality of the studies included in the review and define the most relevant ones, a Quality Assessment table was designed, compiled according to the criteria of the modified JADAD Scale. Using the data, a histogram was developed .All case–control observational studies and cross-sectional studies were evaluated with a low risk of bias, obtaining a quality assessment score of 6 to 8 points, with most of these studies having adjusted for confounding variables. In addition, appropriate case and control definitions and periodontal examination were provided, and validated tools for the assessment of psychological stress and anxiety were used.It has been suggested in the literature that adverse socioeconomic conditions elicit a stress response, which can trigger periodontal inflammation. Wellappulli et al. , Gomaa eThe goal set by Varshini and Rajasekar , WijayaaSeveral studies presented used saliva samples, cortisol, α-amylase, β-endorphin, chromogranin (CgA), salivary IgA, and various other reactive oxygen metabolites ROM to investigate their relationship to periodontitis. The severity of chronic periodontitis was found to increase, with the increase in cortisol levels and salivary reactive. This therefore indicates that the probability of the onset of periodontitis being greater in subjects with a level of cortisol and another reactive is increased. Clinical depression could be a probable risk factor in the development of periodontal disease, especially aggressive periodontitis. As demonstrated by the studies by Ramesh et al.  and FolaThe study by Fenol et al. , conductRajhans et al.  aimed toTo evaluate the association between the influence of work stress and coping style on periodontitis among Japanese workers, Islam et al.  used theIn the study performed by Haririan et al. , the aimThe primary purpose of the study performed by Deng et al.  was to eThe aim in the study by Petit et al. ,31 was tThe cross-sectional study by Rahate et al.  and ZhanMost of the 28 articles included in the study confirm and demonstrate a positive as-sociation between psychological stress and periodontal disease; in detail, two articles examined the positive correlation between stress and gingivitis , while tThe only study, of moderate quality, that was unable to detect this association is that of Haririan et al. . While tNumerous studies have shown the mechanisms through which chronic stress negatively affects periodontal tissues. Stress indirectly affects periodontal health through behavioral and lifestyle changes, amplifying the consumption and abuse of smoking and alcohol, poor diet, negligence in oral hygiene and poor compliance with dental care; it would also seem to influence periodontal health through direct biological impact, mediated through saliva alteration, changes in gingival blood circulation and influencing the host immune response. Future studies should focus on the correlation between the pathology and stress and mainly on possible ways of preventing it.In light of the results obtained from this review, it is important that oral health professionals, also for general health purposes, consider stress factors among the risk factors of periodontal disease, its severity and decreased efficacy of treatments. In patients with chronic stress, it is advisable to carry out brief reminders for periodontal maintenance through constant motivation, strengthening oral hygiene procedures and educating patients on the negative consequences of behaviors used to cope with stress.


We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD.A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred.The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.  NAFLD remains a leading cause of morbidity and mortality globally with 25% of individuals having this condition worldwide.In 2012, several leading gastroenterology and hepatology societies, including the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterology Association (AGA), and the American College of Gastroenterology (ACG) released the initial clinical practice guideline for patients with NAFLD.To further encourage physical activity in patients with NAFLD, the American College of Sports Medicine (ACSM) and their Exercise is Medicine (EIM) initiative was expanded to include NAFLD in 2018.For these reasons, the ACSM convened the inaugural International Multidisciplinary Roundtable on NAFLD and physical activity in July 2022 with the objectives of reviewing and summarizing the biologic, epidemiological, and interventional evidence for the role of physical activity in patients with NAFLD. The purpose of this manuscript is to present the Roundtable findings and conclusions that focused on the relationship between physical activity and NAFLD in terms of (1) NAFLD pathogenesis; (2) screening, advising, and counseling patients with NAFLD about physical activity; (3) providing physical activity recommendations to patients with NAFLD, and (4) outlining future research directions.http://links.lww.com/HC9/A219), each presenter provided a 20-minute overview of their topic followed by a direct question and answer session with the entire Roundtable Faculty. Herein, we provide an overview of the Roundtable presentations and discussions.The ACSM International Multidisciplinary Roundtable on NAFLD was held virtually (in part due to COVID-19 restrictions) on July 7, 2022, with 21 representatives from 18 organizations globally who were invited to participate based on their clinical and research expertise. Three broad topic areas were addressed, including (1) the role of physical activity in NAFLD pathogenesis; (2) screening, advising, and counseling adult patients with NAFLD about physical activity; and (3) providing physical activity recommendations to adult patients with NAFLD. Following individual scoping reviews of the assigned topics  than the general population.Patients with NAFLD have lower cardiorespiratory fitness  which calculates the volume of moderate-to-vigorous physical activity completed  may be considered.When counseling patients about physical activity, it is first important to understand what factors (barriers or enablers) determine whether a person engages or not in behavior. A patient’s capabilities, opportunities, and motivation all play a role.When considering a recommendation for health care providers to counsel patients on exercise, there are no efficacy or comparative effectiveness trials of physician counseling about the benefits of physical activity among patients with NAFLD. However, in non-NAFLD populations with metabolic disease, physician counseling, including the importance of engaging multidisciplinary care teams to promote physical activity has been studied.Several techniques have been used to promote behavior change in patients with NAFLD. Motivational interviewing, which is a technique that is feasible to utilize within a 20-minute clinic visit, can empower patients with NAFLD to make individual health-related decisions,Patients with advanced liver disease, including those with cirrhosis, represent a unique patient population that needs to be viewed independently of patients with earlier stage disease. A recent systematic review summarized the 11 small clinical trials limited exclusively to patients with cirrhosis, including 4 studies which used home-based interventions,Because physicians are not routinely trained in exercise prescription during their medical education, we propose that the exercise specialist should be a key member of the NAFLD treatment team. Avery et alOnce a patient with NAFLD is referred to an exercise specialist, a key focus of the assessment should be to evaluate the patient’s understanding of what NAFLD is and how it relates to their lifestyle behaviors. Additional factors to consider include (1) the patient’s goals for treatment; (2) measurement of current and historical levels of physical activity; (3) assessment of cardiometabolic risk factors, comorbidities, past medical history, and current medications; (4) evaluation of baseline levels of cardiorespiratory fitness as well as functional and exercise capacity; and (5) identification of barriers and facilitators to physical activity participation.To assist the exercise specialist, the ACSM has established guidelines to determine when a medical referral is recommended before starting an exercise training program.When the exercise specialist is designing a training program for patients with NAFLD, the most important consideration is how to tailor exercise for each individual, taking into account baseline capabilities, comorbidities, and personal preferences. Once an exercise program has commenced, there are many management priorities the exercise specialist should be aware of. These include targeting improvement in body weight/body composition, glycemic control, CVD risk factors , cardiorespiratory fitness as well as functional and exercise capacity. The exercise specialist can also play a key role in counseling patients with NAFLD on alcohol intake, smoking cessation, and sleep quality and duration and may be a central person to initiate a referral to other members of the multidisciplinary care team including a dietitian or psychologist where appropriate.Exercise training is well-established as a key component in the clinical management of patients with NAFLD. Previous large systematic reviews, including a recent Cochrane review and those with quantitative meta-analysis, have examined the individual components of the ACSM FITT exercise prescription, including frequency, intensity, time, and type.Despite decades of research, no single optimal exercise prescription has been defined for patients with NAFLD. While the majority of studies have used aerobic exercise training and head-to-head direct comparisons of different exercise modalities are generally lacking, indirect evidence suggests that resistance training may have a role.While most exercise training programs for patients with NAFLD have relied on in-person supervised training, several recent studies have explored the role of telehealth as a means to increase adherence and access to exercise programs. Huber et alFollowing a review of the available primary literature, the ACSM Roundtable identified key knowledge gaps in the existing scientific literature in terms of (1) the role of physical activity in NAFLD pathogenesis; 2) assessing and screening patients with NAFLD for physical activity; (3) advising and counseling patients with NAFLD about the benefits of physical activity; (4) physical activity recommendations in patients with NAFLD; and (5) referring a patient with NAFLD to an exercise specialist (Table  assessinBecause liver fibrosis is closely related with long-term outcomes in patients with NASH, histologic improvement remains the goal of all NASH clinical trials.Many of these knowledge gaps and key unanswered questions remain either from a lack of investigation or from limitations inherent to the scientific literature where included populations across all study designs are heterogenous and often ill-defined. In fact, the majority of interventional studies include all stages of NAFLD with only 3 trials limited only to NASH.In light of these limitations, we look to future grant funding mechanisms to support the research of the highest rigor to answer each and every one of the remaining key knowledge gaps Table .An expert panel reviewed the published scientific evidence and came to a consensus regarding the role of physical activity in patients with NAFLD. The evidence supports that regular physical activity is associated with decreased risk of NAFLD development and that low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. Physical activity screening during routine health care visits in all patients with NAFLD would seem prudent. Moreover, this visit offers a unique opportunity to open a discussion about the many benefits of regular physical activity, many of which may be weight loss independent. If weight loss does occur, this can provide additional benefits. Currently, at least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise program is to be used, the combination of aerobic plus resistance training is preferred, albeit emerging data suggests that HIIT can be considered in select patients instead. Multiple research gaps remain in this field, including the need for studies exploring the mechanistic multiorgan underpinnings of exercise’s benefit, best counseling practices, exercise dosing, and predictors of exercise response. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report and to encourage and support all patients with NAFLD to be as physically active as their age, abilities, and environment will allow. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.


Background: Following the World Health Organization (WHO) recommendation, 38/47 countries have introduced rotavirus vaccines into the program of immunization in the WHO Regional Office for Africa (WHO/AFRO). Initially, two vaccines (Rotarix and Rotateq) were recommended and recently two additional vaccines (Rotavac and Rotasiil) have become available. However, the global supply challenges have increasingly forced some countries in Africa to switch vaccine products. Therefore, the recent WHO pre-qualified vaccines  manufactured in India, offer alternatives and reduce global supply challenges related to rotavirus vaccines; Methods: Using a questionnaire, we administered to the Program Managers, Expanded Program for Immunization, we collected data on vaccine introduction and vaccine switch and the key drivers of the decisions for switching vaccines products, in the WHO/AFRO. Data was also collected fromliterature review and the global new vaccine introduction status data base maintained by WHO and other agencies. Results: Of the 38 countries that introduced the vaccine, 35 (92%) initially adopted Rotateq or Rotarix; and 23% (8/35) switched between products after rotavirus vaccine introduction to either Rotavac (n = 3), Rotasiil (n = 2) or Rotarix (n = 3). Three countries  introduced the rotavirus vaccines manufactured in India. The decision to either introduce or switch to the Indian vaccines was predominately driven by global supply challenges or supply shortage. The withdrawal of Rotateq from the African market, or cost-saving for countries that graduated or in transition from Gavi support was another reason to switch the vaccine; Conclusions: The recently WHO pre-qualified vaccines have offered the countries, opportunities to adopt these cost-effective products, particularly for countries that have graduated or transitioning from full Gavi support, to sustain the demand of vaccines products. Since the World Health Organization (WHO) recommendation for the global introduction of rotavirus vaccine in high disease burden countries , Gavi, tThe early adopted rotavirus vaccines have shown beneficial impact on reducing childhood morbidity and -mortality due to rotavirus and cost-effective in low- and middle income countries ,7,8,9,10The decisions influencing to switching from one vaccine product to another should systematically assess multiple criteria beyond vaccine price include the health, programmatic and economic aspects. Countries should also fully evaluate all product characteristics including product presentation, number of doses per course, cold chain volume, cost of delivery, and wastage . WHO recA number of countries switched from Rotateq or Rotarix to Rotavac, Rotasiil but the reason for the decisions to switch vaccines are not yet fully documented. In this evaluation, we investigated the rotavirus vaccine being used in WHO/AFRO countries and assessed the reasons for switching vaccine products at a country level.https://pubmed.ncbi.nlm.nih.gov/, accessed on 15 February 2023), WHO , International Vaccine Access Center [IVAC]  websites. The data collected included the type of vaccine and if the country had changed or planned to change products since introduction. In addition, the data of current status of global rotavirus introductions was accessed [To assess rotavirus vaccines that are in use in WHO/AFRO countries that participate in the African Rotavirus Surveillance Network introduced in their immunization programs and whether these vaccines had changed since the introduction, we collected information by administering a questionnaire to the Program Managers, Expanded Program for Immunization of the countries that had switched or planning to switch the vaccine product. Data was also collected from literature review by searching the terms or combination of the terms “rotavirus vaccine switch in WHO AFRO” in the PubMed  of the countries in WHO African region had introduced rotavirus vaccines in their national immunization programs, with Nigeria being the most recent country that started phased vaccine introduction from August 2022. Of those, six  are not-eligible for Gavi funding for vaccine introduction and three countries  have graduated or transitioned, and in this case, national Governments must budget and allocate funds for the procurement of vaccines and operational costs for vaccine implementation. The remaining are Gavi Phase III eligible .Of the 38 countries that introduced the rotavirus vaccine in the WHO/AFRO, three  were first time introductions of the recently pre-qualified Indian manufactured vaccines, while the remaining 35 introduced Rotateq or Rotarix. In 2009, when rotavirus vaccination was being rolled out, only two vaccine products were available (Rotateq or Rotarix). However, from the first 35 group of countries to introduce, 23% (n = 8) of the countries have switched the initially adopted rotavirus vaccines to an alternate, recently prequalified Indian vaccines. Among these eight countries that switched, five (63%) adopted Indian manufactured vaccines, with Rotavac being the most frequently adopted (n = 3), while only two have adopted RotaSiiL. The rotavirus vaccines types used during initial introduction in the WHO/AFRO is shown in Six countries  switched from Rotateq to other vaccines because the manufacturer withdrew this vaccine from African market due to undisclosed reasons. Tanzania was recently forced to switch due to the supply shortage. While Ghana’s decision to switch vaccine products was due to cost as the country graduated from GAVI support and had to self-fund the vaccine procurement .In the last decade, we have witnessed the widespread adoption of the two second generation of WHO pre-qualified rotavirus vaccines, internationally licensed for preventing severe illness due to rotavirus diarrhea in high mortality burden countries, particularly in sub-Saharan Africa. The rate of rotavirus vaccine introduction was driven by financial support from Gavi as almost 84% (32/38) of the countries that introduced rotavirus vaccine in their EPI in the WHO/AFRO, did so with Gavi financial support. However, the WHO prequalification of additional two rotavirus vaccines: ROTAVAC™  and RotaSIIL  in 2018 . In addiThese newer vaccines also provided additional options for countries that previously introduced the vaccines to consider more cost-effective vaccines . In the As many countries will transition from Gavi-eligibility in future, more countries will have to find additional resources to procure vaccines and fund their vaccine programs potentially necessitating a switch to a lower cost product. Notably, previous rotavirus vaccine switch that necessitated, the countries were informed about the decision to switch vaccine, meant country had adequate time to plan and manage the switch. More recently, five countries including Kenya, Senegal, Tanzania, Zambia and Zimbabwe have been informed by Gavi to switch from Rotarix to Indian manufactured vaccines (RotasIIL or Rotavac) abruptly due to unforeseen supply constraints. Currently, there is uncertainty in sustainable supply of early adopted rotavirus vaccines for African countries. To mitigate this supply constraints for Rotarix, Uganda notified Gavi of the intention to switch to Indian-manufactured vaccines due to unforeseen supply constraints with their current vaccine product. It is anticipated this unpredictable vaccine supply may erode the gains and documented benefits of rotavirus vaccination in Africa. African governments should support the recent initiatives of vaccine manufacturing as agreed during the African ministerial conference on immunization and Addis declaration  to cushiRotateq vaccine was completely withdrawn and no longer in use in the African region and there is eminent global supply constraint for Rotarix vaccine with five African countries currently affected. Although, the recently WHO pre-qualified vaccines offer opportunities for the countries to adopt these cost-effective products with broader availability, particularly for countries in the trajectory and transitioning from full Gavi support, these challenges emphasizes the need for future vaccines locally manufactured to sustain the local demand while the countries with high birth cohort are rolling out the vaccines  will sustainable supply.The recently WHO pre-qualified vaccines have offered opportunities for more options for the countries to adopt these cost-effective products, particularly for countries that have graduated or transitioning from full Gavi support. Sustained supply of vaccines should be maintained to ensure availability for all countries including those with high birth cohort to reap the full benefits of these vaccination.