Articoli di riviste: "DIARRHEA MITIGATION"

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Abu, Mumuni, e Samuel Codjoe. "Experience and Future Perceived Risk of Floods and Diarrheal Disease in Urban Poor Communities in Accra, Ghana". International Journal of Environmental Research and Public Health 15, n. 12 (12 dicembre 2018): 2830. http://dx.doi.org/10.3390/ijerph15122830.

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Diarrheal disease is a critical health condition in urban areas of developing countries due to increasing urbanization and its associated problems of sanitation and poor access to good drinking water. Increasing floods in cities have been linked to the risk of diarrheal disease. There are few studies that specifically link flooding with diarrhea diseases. This may be due to the fact that secondary data mainly hospital recorded cases, and not individual cases at the household level are used. Furthermore, of the few papers that consider the flood-diarrheal diseases nexus, none have considered risk perceptions in general, and more specifically, whether households that have experienced floods which resulted in a reported case of diarrhea, have higher perceived risks of future occurrences of the two phenomena compared to households that had different experiences. Yet, this is critical for the development of interventions that seek to increase protective behaviors and reduce the risk of contracting diarrhea. We surveyed 401 households in some selected urban poor communities in Accra, the capital of Ghana. Results show that households that experienced floods which resulted in a reported case of diarrhea, have higher perceived risk of future occurrence of the two phenomena compared to other households. We recommend public education that reduces the risk of exposure to flood and diarrhea through flood mitigation measures, including the construction of drains in communities and educating communities on good sanitation.

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McClain, James, J. Boima Kiazolu, Peter Saah Humphrey e Plenseh Diana Paye. "Studies on diarrhea prevalence in selected communities in greater Monrovia, Liberia". International Journal of Basic and Applied Sciences 9, n. 2 (1 giugno 2020): 1. http://dx.doi.org/10.14419/ijbas.v9i2.30570.

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Diarrhea is an epidemic that threatens the livelihood of children less than five years in developing countries. Control and mitigation pose a severe challenge in these countries. The subjective of the study is to assess the prevalence of and factors associated with diarrhea among families in Greater Monrovia. The study recruited 257 families from three communities and geographically and randomly assigned to the two groups (A & B). Socio-demographic survey and knowledge and behavior questionnaires on diarrhea prevalence were used to collect data. Reports from the study indicate that family in Group A (93%) and Group B (83.6%) have significant knowledge associating contaminated drinking water and contaminated food with diarrhea; X2 =11.2, p = 0.001. The family behavior shows that Group A (33%) and Group B (51%) do not treat their drinking water before consumption. The findings from this study recommend an education and awareness intervention on diarrheal and related illnesses to increase family knowledge and improvement of the behavior community public health improvement process.

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Lalani, Tahaniyat, Jamie Fraser, Mark S. Riddle, Ramiro L. Gutierrez, Patrick W. Hickey e David R. Tribble. "Deployment Infectious Disease Threats: IDCRP Initiatives and Vision Forward". Military Medicine 184, Supplement_2 (1 novembre 2019): 26–34. http://dx.doi.org/10.1093/milmed/usz182.

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Abstract Background Infectious diseases pose a significant threat to health and readiness of military personnel deployed globally during wartime and peacekeeping activities. Surveillance and improvement in mitigation through research of infectious disease threats remain an integral part of Force Health Protection. Herein, we review research efforts of the Infectious Disease Clinical Research Program related to deployment and travel-related infections. Methods The objectives of the Deployment and Travel-Related Infections Research Area are to (1) provide epidemiologic and clinical data, including pathogen-specific estimates of disease incidence among deployed troops, (2) execute clinical trials and effectiveness studies to improve recommendations regarding prevention and treatment of infections during deployment, and (3) evaluate the knowledge and practice patterns of health care providers engaged in deployment/travel medicine and the impact on outcomes. The centerpiece protocol of the research area is the Deployment and Travel-Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies cohort study (TravMil), which was initiated in 2010 and collects data on a broad range of deployment-related infections. Results To date, 4,154 deployed military personnel and traveling Department of Defense (DoD) beneficiaries have been enrolled in TravMil. Surveillance data collected through the TravMil study provide assessment of deployment and travel-related infectious disease threats, and the effectiveness of mitigation strategies. The incidence of travelers’ diarrhea, influenza-like illness, and undifferentiated febrile illness is 20.48%, 9.34%, and 6.16%, respectively. The cohort study also provides necessary infrastructure to execute clinical trials. The TrEAT TD clinical trial evaluated the effectiveness of single-dose antibiotic therapy for travelers’ diarrhea in the deployed setting. When compared to levofloxacin, azithromycin was not inferior; however, inferiority was not demonstrated with use of single dose of rifaximin. The trial findings supported the development of a deployment-related health guideline for the management of acute diarrheal disease. A clinical trial evaluating the effectiveness of rifaximin for prevention for travelers’ diarrhea (Prevent TD) is underway. Conclusions The research area has proven its ability to conduct impactful research, including the development of field-expedient diagnostics, the largest DoD multi-site travelers’ diarrhea randomized control trial in peacetime and combat settings, and informed Force Health Protection guidance. The research area continues to provide surveillance data to military commands via an established collaborative network of military treatment facilities, DoD laboratories (both within and outside the continental United States), foreign militaries, and academia. The conduct of clinical and translational research in a deployment setting presents significant challenges, most notably in recruitment/enrollment and compliance with study-related procedures during deployment.

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Niederwerder, Megan. "Risk and Mitigation of African Swine Fever Virus in Feed". Animals 11, n. 3 (18 marzo 2021): 792. http://dx.doi.org/10.3390/ani11030792.

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Since the 2013 introduction of porcine epidemic diarrhea virus into the United States (U.S.), feed and feed ingredients have been recognized as potential routes for the introduction and transmission of foreign animal diseases of swine. Feed ingredients for swine diets are commodities traded worldwide, and the U.S. imports thousands of metric tons of feed ingredients each year from countries with circulating foreign animal diseases. African swine fever (ASF) is the most significant foreign animal disease threat to U.S. swine production, and the recent introduction of ASF into historically negative countries has heightened the risk for further spread. Laboratory investigations have characterized the stability of the ASF virus (ASFV) in feed ingredients subjected to transoceanic shipment conditions, ASFV transmissibility through the natural consumption of plant-based feed, and the mitigation potential of certain feed additives to inactivate ASFV in feed. This review describes the current knowledge of feed as a risk for swine viruses and the opportunities for mitigating the risk to protect U.S. pork production and the global swine population from ASF and other foreign animal diseases.

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Denno, Donna M., Eileen J. Klein, Vincent B. Young, James G. Fox, David Wang e Phillip I. Tarr. "Explaining unexplained diarrhea and associating risks and infections". Animal Health Research Reviews 8, n. 1 (giugno 2007): 69–80. http://dx.doi.org/10.1017/s1466252307001302.

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AbstractGastrointestinal illnesses are common afflictions. However, knowledge of their etiology is often lacking. Moreover, most cases of infections with reportable enteric pathogens (Campylobacter jejuni,Escherichia coliO157:H7,Salmonella,Shigella,Yersinia,CryptosporidiaandGiardia) have sporadic modes of acquisition, yet control measures are often biased towards mitigation of risks discerned by outbreak analysis. To determine the etiology of unexplained diarrhea it is important to study populations that can be matched to appropriate controls and to couple thorough classic microbiologic evaluation on receipt of specimens with archiving and outgrowth capabilities. Research evaluations should address the potential roles of a broad panel of candidate bacterial pathogens including diarrheagenicE. coli,Listeria monocytogenes, Helicobacters andjejuniCampylobacters, and also apply novel massively parallel sequencing and nucleic acid detection technologies that allow the detection of viral pathogens. To fill voids in our knowledge regarding sources of known enteric pathogens it will be critical to extend case-control studies to assess risk factors and exposures to patients with non-epidemic illnesses and to appropriate controls. By filling these gaps in our knowledge it should be possible to formulate rational prevention mechanisms for human gastrointestinal illnesses.

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Pinior, Beate, Clair L. Firth, Veronika Richter, Karin Lebl, Martine Trauffler, Monika Dzieciol, Sabine E. Hutter et al. "A systematic review of financial and economic assessments of bovine viral diarrhea virus (BVDV) prevention and mitigation activities worldwide". Preventive Veterinary Medicine 137 (febbraio 2017): 77–92. http://dx.doi.org/10.1016/j.prevetmed.2016.12.014.

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Chakraborty, Rishika, Khalid M. Khan, Daniel T. Dibaba, Md Alfazal Khan, Ali Ahmed e Mohammad Zahirul Islam. "Health Implications of Drinking Water Salinity in Coastal Areas of Bangladesh". International Journal of Environmental Research and Public Health 16, n. 19 (4 ottobre 2019): 3746. http://dx.doi.org/10.3390/ijerph16193746.

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Coastal areas in South Asian countries are particularly vulnerable to elevated water salinity. Drinking water salinity has been found to be associated with cardiovascular diseases (CVD), diarrhea, and abdominal pain. Our study aimed to find if excess drinking water salinity was associated with increased hospital visits with an array of health effects in coastal sub-districts of Bangladesh. A cross-sectional study was conducted with 157 participants from three coastal sub-districts. A face-to-face interview was conducted to collect salinity exposure and hospital visit data. Water samples were collected from both drinking and other household water sources for the measurement of salinity and total dissolved solids (TDS). CVD, diarrhea, and abdominal pain related hospital visits were found to be significantly associated with high water salinity and TDS. Households exposed to high salinity demonstrated a higher frequency of hospital visits than the low salinity-exposed households. People exposed to high salinity seemed to lack awareness regarding salinity-inducing health effects. Water salinity is a public health concern that will continue to rise due to climate change. Therefore, raising awareness about the health risks of water salinity is essential for the government to frame policies and mitigation strategies to control this emerging threat.

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Xue, Zhiqiang, Zhenbo Yang, Hui Sun, Jinghuan Ren, Mengzi Sun, Jiagen Li, Anning Zhang et al. "Epidemiological analysis of respiratory and intestinal infectious diseases in three counties of Sichuan: the baseline survey of Disaster Mitigation Demonstration Area in western China". PeerJ 7 (23 luglio 2019): e7341. http://dx.doi.org/10.7717/peerj.7341.

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Background Natural disasters can indirectly induce epidemics of infectious diseases through air and water pollution, accelerated pathogen reproduction, and population migration. This study aimed to explore the epidemiological characteristics of the main infectious diseases in Sichuan, a province with a high frequency of natural disasters. Methods Data were collected from the local Centers for Disease Control infectious disease reports from Lu, Shifang and Yuexi counties from 2011 to 2015 and from the baseline survey of the Disaster Mitigation Demonstration Area in Western China in 2016. Principal component regression was used to explore the main influencing factors of respiratory infectious diseases (RIDs). Results The incidence rates of RIDs and intestinal infectious diseases (IIDs) in 2015 were 78.99/100,000, 125.53/100,000, 190.32/100,000 and 51.70/100,000, 206.00/100,000, 69.16/100,000 in Lu, Shifang and Yuexi respectively. The incidence rates of pulmonary tuberculosis (TB) was the highest among RIDs in the three counties. The main IIDs in Lu and Shifang were hand-foot-mouth disease (HFMD) and other infectious diarrhea; however, the main IIDs in Yuexi was bacillary dysentery. The proportions of illiterate and ethnic minorities and per capita disposable income were the top three influencing factors of RIDs. Conclusions TB was the key point of RIDs prevention among the three counties. The key preventable IIDs in Lu and Shifang were HFMD and other infectious diarrhea, and bacillary dysentery was the major IIDs in Yuexi. The incidence rates of RIDs was associated with the population composition, the economy and personal hygiene habits.

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Gebhardt, J. T., J. C. Woodworth, M. D. Tokach, J. M. DeRouchey, R. D. Goodband, C. K. Jones e S. S. Dritz. "285 Medium Chain Fatty Acid Mitigation Activity Against Porcine Epidemic Diarrhea Virus (PEDV) in Nursery Pig Diets after 40 d of Storage." Journal of Animal Science 96, suppl_2 (aprile 2018): 153. http://dx.doi.org/10.1093/jas/sky073.282.

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Cochrane, R. A., L. L. Schumacher, S. S. Dritz, J. C. Woodworth, A. R. Huss, C. R. Stark, J. M. DeRouchey et al. "Effect of pelleting on survival of porcine epidemic diarrhea virus–contaminated feed". Journal of Animal Science 95, n. 3 (1 marzo 2017): 1170–78. http://dx.doi.org/10.2527/jas.2016.0961.

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Abstract Porcine epidemic diarrhea virus (PEDV) is a heat-sensitive virus that has devastated the U.S. swine industry. Because of its heat sensitivity, we hypothesized that a steam conditioner and pellet mill mimicking traditional commercial thermal processing may mitigate PEDV infectivity. Pelleting, a common feed processing method, includes the use of steam and shear forces, resulting in increased temperature of the processed feed. Two thermal processing experiments were designed to determine if different pellet mill conditioner retention times and temperatures would impact PEDV quantity and infectivity by analysis of quantitative reverse transcription PCR and bioassay. In Exp. 1, a 3 · 3 · 2 factorial design was used with 3 pelleting temperatures (68.3, 79.4, and 90.6°C), 3 conditioning times (45, 90, or 180 s), and 2 doses of viral inoculation (low, 1 · 102 tissue culture infectious dose50 (the concentration used to see cytopathic effect in 50% of the cells)/g, or high, 1 · 104 tissue culture infectious dose50/g). Noninoculated and PEDV-inoculated unprocessed mash were used as controls. The low-dose PEDV–infected mash had 6.8 ± 1.8 cycle threshold (Ct) greater (P < 0.05) PEDV than the high-dose mash. Regardless of time or temperature, pelleting reduced (P < 0.05) the quantity of detectable viral PEDV RNA compared with the PEDV-inoculated unprocessed mash. Fecal swabs from pigs inoculated with the PEDV-positive unprocessed mash, regardless of dose, were clinically PEDV positive from 2 to 7 d (end of the trial) after inoculation. However, if either PEDV dose of inoculated feed was pelleted at any of the 9 tested conditioning time · temperature combinations, no PEDV RNA was detected in fecal swabs or cecum content. Based on Exp. 1 results, a second experiment was developed to determine the impact of lower processing temperatures on PEDV quantity and infectivity. In Exp. 2, PEDV-inoculated feed was pelleted at 1 of 5 conditioning temperatures (37.8, 46.1, 54.4, 62.8, and 71.1°C) for 30 s. The 5 increasing processing temperatures led to feed with respective mean Ct values of 32.5, 34.6, 37.0, 36.5, and 36.7, respectively. All samples had detectable PEDV RNA. However, infectivity was detected by bioassay only in pigs from the 37.8 and 46.1°C conditioning temperatures. Experiment 2 results suggest conditioning and pelleting temperatures above 54.4°C could be effective in reducing the quantity and infectivity of PEDV in swine feed. However, additional research is needed to prevent subsequent recontamination after pelleting as it is a point-in-time mitigation step.

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Li, Wentao, Lixia Kai, Zipeng Jiang, Huan He, Mingzhi Yang, Weifa Su, Yizhen Wang, Mingliang Jin e Zeqing Lu. "Bifidobacterium longum, Lactobacillus plantarum and Pediococcus acidilactici Reversed ETEC-Inducing Intestinal Inflammation in Mice". Microorganisms 10, n. 12 (28 novembre 2022): 2350. http://dx.doi.org/10.3390/microorganisms10122350.

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Microecological preparation could relieve Enterotoxigenic Escherichia coli (ETEC) K88-induced diarrhea in piglets, but which bacteria play a key role and the mitigation mechanism have not been fully clarified. In this study, 36 male mice were randomly divided into six groups (CON, K88, BK (Bifidobacterium longum + K88), LK (Lactobacillus plantarum + K88), PK (Pediococcus acidilactici + K88), and MK (mixed strains + K88)) to explore the prevention mechanisms. Three probiotic strains and their mixtures (TPSM) significantly relieved the weight loss and restored the ratio of villus height to crypt depth in the jejunum. Except for Bifidobacterium longum, other strains significantly decreased interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in mice serum. The TPSM treatment significantly downregulated the mRNA expression of the inflammatory cytokines and the Toll-like receptor and downstream gene (TLR4, MyD88, NF-κB) in jejunum induced by ETEC. Furthermore, the TPSM could restore dysbiosis of the intestinal microbiota caused by ETEC. The intestinal microbiota analysis demonstrated that Bifidobacterium longum enriched the Bifidobacterium genus (p < 0.05), Lactobacillus plantarum enriched the Lactobacillus genus (p < 0.05), Pediococcus acidilactici enriched the Coriobacteriaceae_UCG-002 and Christensenellaceae_R-7_group genus (p < 0.05), mixed bacteria enriched the Akkermansia genus (p < 0.05), but ETEC enriched the Desulfovibrio genus (p < 0.05). Meanwhile, the starch and sucrose metabolism, galactose and fructose metabolism, mannose metabolism and ABC transporters were increased with probiotics pre-treatment (p < 0.05). To sum up, the microecological preparation alleviated ETEC-induced diarrhea by regulating the immune response, rebalancing intestinal microbiota and improving carbohydrate metabolism.

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Coble, Kyle. "248 U.S. Challenges with E. Coli and Road map for the Future". Journal of Animal Science 100, Supplement_3 (21 settembre 2022): 126–27. http://dx.doi.org/10.1093/jas/skac247.242.

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Abstract In recent years U.S pork producers have been faced with what seems to be a never-ending uphill battle, with Enterotoxigenic E. coli which causes severe post weaning diarrhea and mortality. Numerous hypotheses ranging from pig genetics to changes in bacterial resistance have all been discussed as potential causes, but no clear answer has been provided to date. Over the past two years, many nutritional strategies (low crude protein, higher fiber diets, etc.) aimed at mitigating the deleterious effects of ETEC have been tried in both field and research nurseries with varying success. There is a concerted effort across the industry to better understand E. coli and possible mitigation and prevention strategies. However, to be successful we need to understand that controlling E. coli is a multidisciplinary issue that requires understanding how each piece of the puzzle impacts E. coli. Production practices, veterinarian protocols, stress events (weaning, transportation), temperature, and clear plans for a world post pharmacological levels of zinc and feed grade medications all contribute to the success of mitigating/eliminating ETEC. While the pig demands we find solutions quickly, the sustainability of healthy swine production and lower production cost require us to find the root source. This requires starting at the beginning of the process and piecing the puzzle together. We need research at all levels of production to understand key triggers–actions and reactions. What things are we doing in the farrowing crate today that impacts this? When pigs are placed in the nursery, what is the required temperature for newly weaned pigs? Are there possibly production practices that have benefits in one place and harsh impacts in another? These are examples of questions needing answered. To fix an issue of this magnitude, you must understand it simply – and we simply do not understand this issue well enough today.

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Wibowo, Nugroho Ari. "Peran Postaga Dalam Pemberdayaan Kesiapsiagaan Masyarakat Dalpenang Sampang". AKSIOLOGIYA : Jurnal Pengabdian Kepada Masyarakat 1, n. 2 (21 luglio 2017): 119. http://dx.doi.org/10.30651/aks.v1i2.890.

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BNPB (2012) stated that casualties affected from the year 1815-2011 continue to increase. The disaster that struck Indonesia destroyed the development that has grown with great difficulty. Such conditions can cause both material and immaterial losses. The most disadvantaged are the marginalized and the poor. MLHPB (2016) states every rainy season Sampang is sure to be drowned by the flood. Data collected by MLHPB in Dalpenang and Rong Tengah were expressed as 35.4% of people suffering from leptospirosis, 60.3% of people suffering from pyoderma or ulceration, and the remaining 4.3% are inactive, lower, and diarrhea. This becomes a complex problem and there is no clear step to overcome the routine problem of it. In addition, interrupted, the distribution of drugs and. The established regulation is also considered ineffective. Need an active role of the community who are members of Posyandu Emergency Response to overcome the above problems. The methods undertaken in IbM's activities are posyandu building and disaster response. Disaster response programs ranging from the mitigation phase to the rehabilitation phase with extension and training approaches involving traditional leaders as mass mobilisers. The result of this IBM Service Activity is 80% of participants are able to understand the counseling about flood prevention and flood prevention, the cadres are able to do first aid in emergency disasters, and 80% of cadres are able to make prevention and mitigation efforts of flood. Awareness raising of disaster partners and natural disasters that are more capable and self-sufficient in facing the flood disaster each year.

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Mclean, A. J., e J. M. Shultz. "(A-309) Flood Disaster Averted: Red River Resilience". Prehospital and Disaster Medicine 26, S1 (maggio 2011): s87. http://dx.doi.org/10.1017/s1049023x1100433x.

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Flood Disaster Averted: Red River Resilience It is estimated that floods make up 40% of all natural disasters and that the majority of natural disaster deaths are attributable to these events. The vast majority of literature on mental health and disaster revolves around response and recovery after the event. Mitigation of flooding can have a tremendous impact on health, including the prevention of common physical ailments including diarrhea, hepatitis, typhoid, tetanus, malnutrition, dermatologic conditions, orthopedic injuries, etc… It can also reduce mental health difficulties including stress, anxiety, depression, PTSD and other disorders. Psychosocial reactions to trauma are recognized to be among the most long-term and debilitating outcomes of disasters. This presentation describes a community's successful efforts to prevent a major flood disaster in the midst of a changing risk landscape. The authors focus on factors contributing to the resilience of a community in the upper Midwest of the United States in responding to the threat of a catastrophic natural disaster. In addition, the presentation includes the building blocks for successful integration of mental health presence through all phases of disaster: mitigation, preparedness, response and recovery. Andrew J. McLean, MD Medical Director, Department of Human Services, State of North Dakota. 2624 9th Ave. SW, Fargo, ND 58103 ajmclean@nd.gov, amclean@medicine.nodak.edu James M. Shultz, MS PhD. Director, Center for Disaster & Extreme Event Preparedness (DEEP Center) University of Miami Miller School of Medicine, Clinical Research Building 1120 NW 14 St., Miami, FL 33160, USA and Partner, High-Alert International, Orlando, FL, USA 305-219-9011 jamesmichaelshultz@gmail.com. jshultz1@med.miami.edu. jshultz@high-alert.com.

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Harrison, O. L., G. E. Nichols, J. T. Gebhardt, Cassandra K. Jones, Jason C. Woodworth, S. S. K. Dritz, J. Bai et al. "PSVI-4 Efficacy of Medium Chain Fatty Acids and Fatty Acid-based Feed Additives as a Mitigation Strategy Against Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus". Journal of Animal Science 99, Supplement_1 (1 maggio 2021): 216–17. http://dx.doi.org/10.1093/jas/skab054.354.

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Abstract Recent research has demonstrated that swine viruses can be transmitted via feed. Chemical feed additives have been suggested for the mitigation of these viruses in complete feed. Therefore, the objective of this study was to evaluate the efficacy of a commercially available formaldehyde-based feed additive, medium chain fatty acid blend (MCFA), and commercially available fatty acid-based products for mitigation of porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV) in a feed matrix. Treatments consisted of: 1) non-treated positive control, 2) 0.33% commercial formaldehyde-based product (Sal Curb; Kemin Industries, Inc.; Des Moines, IA), 3) 0.5% MCFA blend (1:1:1 ratio of C6:0, C8:0, and C10:0, Sigma Aldrich, St. Louis, MO), 4) 0.25%, 5) 0.5%, or 6) 1% of commercial dry mono and diglyceride-based product (Furst Strike; Furst-McNess Company, Freeport, IL), 7) 0.25%, 8) 0.5%, or 9) 1% of commercial dry mono and diglyceride-based product (Furst Protect; Furst-McNess Company, Freeport, IL), 10) 0.25%, 11) 0.5%, or 12) 1% dry mono and diglyceride-based experimental product (Furst-McNess Company, Freeport, IL) with 3 replications/treatment. Treatments were applied to complete swine feed before inoculation with 106 TCID50/g of feed with PEDV or PRRSV. Post inoculation feed was held at ambient temperature for 24 h before being analyzed via qRT-PCR. The analyzed values represent the cycle threshold. Formaldehyde and MCFA decreased (P < 0.05) the detectable RNA of PEDV and PRRSV compared to all other treatments. Furst Strike, Furst Protect, and the experimental product did not significantly impact detectability of PEDV or PRRSV RNA. In conclusion, MCFA and formaldehyde treatments are effective at reducing detection of RNA from PEDV and PRRSV in feed.

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Gebhardt, Jordan T., Jason C. Woodworth, Cassandra K. Jones, Mike D. Tokach, Philip C. Gauger, Rodger G. Main, Jianqiang Zhang et al. "Determining the impact of commercial feed additives as potential porcine epidemic diarrhea virus mitigation strategies as determined by polymerase chain reaction analysis and bioassay1". Translational Animal Science 3, n. 1 (20 agosto 2018): 93–102. http://dx.doi.org/10.1093/tas/txy100.

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Abstract Mitigation of porcine epidemic diarrhea virus (PEDV) was assessed using two feed additives (0.5% inclusion of a benzoic acid [BA] product and 0.02% inclusion of an essential oil [EO] product; DSM Nutritional Products Inc., Parsippany, NJ), and combination of both products (0.5% BA and 0.02% EO) in spray-dried porcine plasma (SDPP) and a swine gestation diet (FEED) as determined by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and bioassay. Viral RNA quantification was performed at 7 sampling days post-laboratory inoculation (d 0, 1, 3, 7, 14, 21, and 42) and infectivity was assessed via bioassay with 10-d-old pigs. There was a tendency for treatment × feed matrix × day interaction (P = 0.094), in which the cycle threshold (Ct) value increased over time in FEED when treated with both feed additives, whereas there was no increase over time observed in SDPP treated with both feed additives. There was a feed matrix × day interaction (P < 0.001) in which Ct increased over time in FEED, whereas very little increase over time was observed in SDPP. A tendency for a treatment × feed matrix effect (P = 0.085) was observed where FEED treated with the combination of EO and BA had a greater (P < 0.05) PEDV Ct value than other FEED treatments, and all SDPP treatments had the lower PEDV Ct values compared to FEED treatments (P < 0.05). Overall, the combination of both feed additives was most effective at reducing the quantity of genetic material as detected by qRT-PCR (P < 0.001) compared to either additive alone or no feed additive. Virus shedding was observed in the d 7 postinoculation SDPP treatment that was treated with both feed additives, as well as d 0 untreated FEED and d 0 FEED treated with both feed additives. No other treatment bioassay room had detectible RNA shed and detected in fecal swabs or cecal contents. In summary, the combination of EO and BA enhanced the degradation of PEDV RNA in feed but had little impact on RNA degradation in SDPP. Both untreated feed and feed treated with the combination of EO and BA resulted in infection at d 0 post-laboratory inoculation; however, neither set of samples was infective at d 1 postinoculation. In addition, SDPP harbored greater levels of quantifiable RNA for a longer duration of time compared to FEED, and these viral particles remained viable for a longer duration of time indicating differences in viral stability exist between different feed matrices.

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Ehsan, Sana, Farhat Abbas, Muhammad Ibrahim, Bashir Ahmad e Aitazaz A. Farooque. "Thermal Discomfort Levels, Building Design Concepts, and Some Heat Mitigation Strategies in Low-Income Communities of a South Asian City". International Journal of Environmental Research and Public Health 18, n. 5 (4 marzo 2021): 2535. http://dx.doi.org/10.3390/ijerph18052535.

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Heat stress provokes thermal discomfort to people living in semiarid and arid climates. This study evaluates thermal discomfort levels, building design concepts, and some heat mitigation strategies in low-income neighborhoods of Faisalabad, Pakistan. The outdoor and indoor weather data are collected from April to August 2016 using a weather station installed ad hoc in urban settings, and the 52 houses of the five low-income participating communities living in congested and less environment-friendly areas of Faisalabad. The discomfort index values, related to the building design concepts, including (i) house orientation to sunlight and (ii) house ventilation, are calculated from outdoor and indoor dry-bulb and wet-bulb temperatures. Our results show that although June was the hottest month of summer 2016, based on the monthly mean temperature of the Faisalabad region, the month of May produced the highest discomfort levels, which were higher in houses exposed to sunlight and without ventilation. The study also identifies some popular heat mitigation strategies adopted by the five participating low-income communities during various heat-related health complaints. The strategies are gender-biased and have medical, cultural/customary backgrounds. For example, about 52% of the males and 28% of the females drank more water during dehydration, diarrhea, and eye infection. Over 11% and 19% of the males and females, respectively, moved to cooler places during fever. About 43% of the males and 51% of the females took water showers and rested to combat flu (runny nose), headache, and nosebleed. The people did not know how to cure muscular fatigue, skin allergy (from a type of Milia), and mild temperature. Planting trees in an area and developing open parks with greenery and thick canopy trees can be beneficial for neighborhoods resembling those evaluated in this study.

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Thomas, Ronnie, Bins M. John, Joe Thomas Koothapally, Sanjeev Kumar, Supriya Adiody, Venu Balachandran, Chithra Valsan e Praveenlal Kuttichira. "Clinical and epidemiological spectrum of coronavirus disease 2019 in Central Kerala: a retrospective case series". International Journal Of Community Medicine And Public Health 8, n. 3 (24 febbraio 2021): 1503. http://dx.doi.org/10.18203/2394-6040.ijcmph20210852.

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Kerala state in India was known for its early response to the Covid-19 pandemic by public health mitigation measures through science-based advocacy. The objective of this study was to analyze epidemiological and clinical characteristics of COVID-19 patients admitted to a tertiary care center in central Kerala. This retrospective case series was undertaken by reviewing the medical records and extracting the epidemiological data, clinical symptoms and laboratory findings of consecutive patients admitted between April 1st and September 31, 2020. Clinical and demographic parameters of hospitalized patients were analyzed regarding their association with the severity of disease. The mean age of the patients was 35.8 years with significant male predominance. Shopkeepers represented 15.6% of the patients and healthcare workers represented 12.5%. Primary contact with a known case was documented in 62.5% of the patients. Asymptomatic patients constituted 25% of the patients and the most commonly experienced symptoms were fever, cough, breathlessness and diarrhea. Three patients had atypical presentations in the form of generalized seizures, intussusception and generalized anxiety with suicidal ideation. Neutrophilia and Lymphopenia were the most dominant laboratory finding. The clinical spectrum of COVID-19 in the study population is wider than previously described in literature.

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Silva, Salomão Brandi da, e Cristina Aparecida Gomes Nassar. "Matriz de impacto para gestão de microbacias com ótica na produtividade agropecuária sustentável e na saúde da população rural: Estudo de caso em quatro regiões da microbacia Rio do Colégio – São Fidélis – RJ". Revista Eletrônica em Gestão, Educação e Tecnologia Ambiental 20, n. 1 (1 marzo 2016): 211. http://dx.doi.org/10.5902/2236117019967.

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The present work aimed to evaluate the preservation of natural resources River College watershed as well as the health of the rural population. The watershed was divided into sub-areas which were visited, and interviews conducted microbiological analysis of water. An impact matrix based on population health, rural sanitation and the use of natural resources was created. The matrix was effective in identifying the main impacts in each region of the watershed. The highest incidence sewage peridomicilary, was found in the regions of Santo Aleixo and Toca Fria. Lack of management with cattle was a problem observed in all regions analyzed, resulting in a significant increase in E. coli coliform. All interviewed population consumes untreated water. In regions of the Toca Fria, Santo Aleixo and Aracaju the population makes use of free nascent of contamination from domestic sewage, but with access to cattle in most cases. In the Rio do Colégio region some families use water from the main course. High rates of diarrhea and worms coincide with the areas of greatest significance of impact indicated by the matrix. Mitigation measures were presented low economic cost and with high visibility to characterized impacts.

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Meki, Chisala D., Esper J. Ncube e Kuku Voyi. "Frameworks for mitigating the risk of waterborne diarrheal diseases: A scoping review". PLOS ONE 17, n. 12 (9 dicembre 2022): e0278184. http://dx.doi.org/10.1371/journal.pone.0278184.

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Background Diarrhea is one of the major cause of death and morbidity around the world. Objectives This scoping review summarizes existing frameworks that aim to mitigate the risks of waterborne diarrheal diseases and describe the strengths and weaknesses of these frameworks. Eligibility criteria Published frameworks designed to mitigate the risks of waterborne diarrheal diseases. Frameworks published in English, from around the world and published since inception to date. Sources of evidence PubMed, Scopus, Web of Science, Google Scholar, Google Free Search, organization websites and reference lists of identified sources. Charting methods Data were charted using the Joanna Briggs Institute tool. Results were summarized and described narratively. A criterion to score the strengths and weaknesses of the included frameworks was also developed. Results Five frameworks were identified including: the hygiene improvement framework, community led total sanitation, global action plan for pneumonia and diarrhea, participatory hygiene and sanitation transformation, and sanitation and family education. These frameworks shared several common components, including identification of problems and risk factors, identification and implementation of interventions, and evaluation and monitoring. The frameworks had several interventions including different infrastructure, health promotion and education, enabling environment and clinical treatments. Most of the frameworks included health promotion and education. All the frameworks were strengthened by including strategies for implementing and delivering intervention, human resource aspect, community involvement, monitoring, and evaluation. The main weakness included not having components for collecting, storing, and transferring electronic data and the frameworks not being specifically for mitigating waterborne diarrheal diseases. In addition, the identified frameworks were found to be effective in mitigating the risk of diarrhea diseases among other health effects. Conclusions Existing frameworks should be updated specifically for mitigating waterborne diarrheal diseases that includes the strengths and addresses weaknesses of reviewed frameworks.

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Pluske, John. "103 The Role of Crude Protein in Reducing the Need for Antibiotics in the Post-weaning Period". Journal of Animal Science 99, Supplement_1 (1 maggio 2021): 102. http://dx.doi.org/10.1093/jas/skab054.164.

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Abstract For many decades, antimicrobial compounds such as antibiotics and some mineral compounds have been used in pork production to promote pig growth and survival after weaning through mitigation of subclinical and clinical diseases, such as enterotoxigenic strains of Escherichia coli. Bans and restrictions in the use of some antimicrobial compounds has led, often out of necessity, to the development of alternative feeding strategies to address these challenges. One tool to reduce the post-weaning malaise in the absence of specific antimicrobial compounds is manipulation of the protein content of diets offered to pigs. Numerous studies have shown that feeding higher crude protein diets in the post-weaning period, usually in the absence of specific antimicrobials, is generally related to decreased fecal consistency (looser stools) and an increased incidence of post-weaning diarrhea. In some cases, this causes more therapeutic antibiotic administrations, more animal care, and a greater mortality. Production indices are poorer as a consequence. Conversely, feeding diets of lower crude protein content after weaning has typically been associated with better health outcomes, but if diets are not correctly formulated with the addition of appropriate crystalline amino acids, then production outcomes can suffer. Increasing the quantity of fermentable protein entering the cecum and colon by feeding more dietary protein will stimulate changes in microbial composition, with the microbiota shifting to a more N-utilizing community resulting in greater protein catabolic activity and the increased production of products including ammonia, amines and branched-chain fatty acids. This, in turn, can be associated with increased diarrhea. Formulating starter diets that limit the flow of exogenous and endogenous proteinaceous compounds posteriorly to the ileo-caecal valve can be used to reduce the post-weaning malaise and may minimize the use of certain antimicrobial compounds. However, feeding lower-protein diets alone is not always the panacea to this production issue, and will likely need to be used in conjunction with other targeted nutritional and health measures specific to the farm in question.

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Keaton, Amelia, Rashida Hassan, Sarah Luna, Isabell Lee, Richelle Magalhaes, Matthew Bidlack, Paul Graf et al. "678. Outbreak of Shiga Toxin-Producing Escherichia coli Infections at Marine Corps Recruit Depot (MCRD), San Diego and Camp Pendleton, California: October–November, 2017". Open Forum Infectious Diseases 5, suppl_1 (novembre 2018): S244—S245. http://dx.doi.org/10.1093/ofid/ofy210.684.

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Abstract Background Shiga toxin-producing Escherichia coli (STEC) infections are a major cause of foodborne illness and the principal cause of hemolytic-uremic syndrome (HUS). In November 2017, CDC and the US Navy responded to an outbreak of STEC illnesses in military recruits at the Marine Corps Recruit Depot in San Diego (MCRD). We investigated to determine the source of this outbreak and identify prevention and mitigation measures. Methods In October 2017, medical staff identified a high number of gastrointestinal (GI) illnesses at MCRD. Recruits with diarrhea submitted stool specimens for culture and/or culture-independent diagnostic testing (CIDT) for GI pathogens. We performed pulsed-field gel electrophoresis (PFGE) on culture isolates. Case-patients were defined as confirmed (PFGE-confirmed STEC infection matching outbreak strains), probable (diagnosis of HUS and/or CIDT evidence of STEC), or suspected (bloody diarrhea). We conducted environmental evaluations of dining facilities, training areas, and barracks. A case–control study was performed using PFGE-confirmed case-patients and platoon-matched controls. We performed product traceback for foods identified as exposure risks by interview or case–control study. Results We identified 64 confirmed, 105 probable, and 91 suspected case-patients. Thirty case-patients required hospitalization and 15 had HUS. Ages ranged from 17 to 28 years (median: 18 years). Poor hygiene practices among recruits and inconsistent cooking temperatures within dining facilities were noted. Forty-three case-patients and 135 controls were interviewed about food, hygiene, and environmental exposures. Consumption of undercooked beef was significantly associated with illness (mOR 2.40, CI 1.04–5.72, P = 0.04). We identified a single ground beef supplier for MCRD, but dining facility records did not document the dates on which specific lots of ground beef were used. Conclusion Case–control analysis and environmental observations suggested undercooked ground beef as a potential source for this outbreak. We recommended the Navy and Marine Corps retain lot information, address food handling concerns, and improve hygiene among recruits. Disclosures All authors: No reported disclosures.

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Stewart, Savannah C., Steve S. Dritz, Jason C. Woodworth, Chad Paulk e Cassandra K. Jones. "A review of strategies to impact swine feed biosecurity". Animal Health Research Reviews 21, n. 1 (giugno 2020): 61–68. http://dx.doi.org/10.1017/s146625231900015x.

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AbstractGlobal pork production has largely adopted on-farm biosecurity to minimize vectors of disease transmission and protect swine health. Feed and ingredients were not originally thought to be substantial vectors, but recent incidents have demonstrated their ability to harbor disease. The objective of this paper is to review the potential role of swine feed as a disease vector and describe biosecurity measures that have been evaluated as a way of maintaining swine health. Recent research has demonstrated that viruses such as porcine epidemic diarrhea virus and African Swine Fever Virus can survive conditions of transboundary shipment in soybean meal, lysine, and complete feed, and contaminated feed can cause animal illness. Recent research has focused on potential methods of preventing feed-based pathogens from infecting pigs, including prevention of entry to the feed system, mitigation by thermal processing, or decontamination by chemical additives. Strategies have been designed to understand the spread of pathogens throughout the feed manufacturing environment, including potential batch-to-batch carryover, thus reducing transmission risk. In summary, the focus on feed biosecurity in recent years is warranted, but additional research is needed to further understand the risk and identify cost-effective approaches to maintain feed biosecurity as a way of protecting swine health.

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Zhang, Siteng, Yu Cao, Zixuan Wang, Huanhuan Liu, Yue Teng, Guopeng Li, Jiaxiu Liu e Xiaodong Xia. "Fermented Sargassum fusiforme Mitigates Ulcerative Colitis in Mice by Regulating the Intestinal Barrier, Oxidative Stress, and the NF-κB Pathway". Foods 12, n. 10 (9 maggio 2023): 1928. http://dx.doi.org/10.3390/foods12101928.

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In recent years, Sargassum fusiforme has gained increasing attention for its ability to improve human health and reduce the risk of disease. Nevertheless, there have been few reports on the beneficial functions of fermented Sargassum fusiforme. In this study, the role of fermented Sargassum fusiforme in the mitigation of ulcerative colitis was investigated. Both fermented and unfermented Sargassum fusiforme demonstrated significant improvement in weight loss, diarrhea, bloody stools, and colon shortening in mice with acute colitis. Fermented Sargassum fusiforme further protected against goblet cell loss, decreased intestinal epithelium permeability, and enhanced the expression of tight junction proteins. Fermented Sargassum fusiforme reduced oxidative stress, which was demonstrated by a decrease in nitric oxide (NO), myeloperoxidase (MPO), and malondialdehyde (MDA) concentrations in the colon of mice and an increase in total superoxide dismutase (T-SOD) activity in the colon. Meanwhile, catalase (CAT) concentrations in both the colon and serum of mice were significantly increased. Fermented Sargassum fusiforme also attenuated the inflammatory response, which was evidenced by the decreased level of pro-inflammatory cytokines in the colon. Moreover, fermented Sargassum fusiforme inhibited the nuclear factor-κB (NF-κB) signaling pathway and increased the production of short-chain fatty acids in the intestine. These findings indicate that fermented Sargassum fusiforme may have the potential to be developed as an alternative strategy for alleviating colitis.

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Lerner, Annie B., Roger A. Cochrane, Jordan T. Gebhardt, Steve S. Dritz, Cassandra K. Jones, Mike D. Tokach, Robert D. Goodband et al. "72 Young Scholar Presentation: Use of medium chain fatty acids as mitigation or prevention strategies against pathogens in swine feed". Journal of Animal Science 98, Supplement_3 (2 novembre 2020): 59–60. http://dx.doi.org/10.1093/jas/skaa054.106.

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Abstract Four experiments were conducted to evaluate: 1) medium chain fatty acids (MCFA) application to swine feed pre- or post-viral contamination with porcine epidemic diarrhea virus (PEDV) measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), 2) MCFA levels and combinations measured by qRT-PCR, and 3) selected MCFA in bioassay. In Exp. 1, treatments were a 2x2 + 1 factorial with the main effects of chemical treatment (0.3% commercial formaldehyde (CF), Sal CURB [Kemin Industries, Des Moines, IA] or 1% MCFA blend (Blend) of 1:1:1 C6:C8:C10 [PMI, Arden Hills, MN]) and timing of application pre- or post-inoculation with PEDV; plus a positive control (PC; feed inoculated with PEDV and no chemical treatment). All combinations of treatment and timing decreased detectable PEDV compared to PC (P< 0.05). Pre-inoculation had decreased PEDV detection compared to post-inoculation (P=0.009). Commercial formaldehyde decreased PEDV detection compared to MCFA (P< 0.001). In Exp. 2 and 3, pre-inoculation treatments consisted of: 1) PC, 2) 0.3% CF, and varying levels (0.125-0.66%) and combinations of MCFA (C5:0, C6:0, C8:0, or C10:0). In Exp. 2, treating feed with 0.33% C8:0 decreased (P< 0.05) PEDV detection compared to all levels of MCFA and PC. In Exp. 3, treating feed with CF, 0.5-1% Blend, all levels of C6:0+C8:0, 0.25% C6:0+C10:0, 0.33% C6:0+C10:0, 0.25% C8:0+C10:0, or 0.33% C8:0 + 0.33% C10:0 resulted in decreased PEDV detection compared to PC (P< 0.05). In Exp. 4, feed was treated pre-inoculation with either 1) no treatment (PC), 2) 0.3% CF, 3) 0.5% Blend, or 4) 0.3% C8:0 and analyzed via qRT-PCR and bioassay. Adding 0.5% Blend or 0.3% C8:0 resulted in decreased PEDV detection compared to PC. All chemical treatments resulted in no evidence of infectivity in the bioassay while the positive control did produce evidence of infectivity. In conclusion, lower levels of MCFA than previously evaluated may provide in-feed protection against PEDV.

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Marx, Gavin M., Amy Jo Chien, José A. García-Sáenz, Arlene Chan, Manuel Ruiz-Borrego, Carlos Hernando Barcenas, Michael P. Thirlwell et al. "Dose escalation for mitigating diarrhea: Ranked tolerability assessment of anti-diarrheal regimens in patients receiving neratinib for early-stage breast cancer." Journal of Clinical Oncology 39, n. 15_suppl (20 maggio 2021): 536. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.536.

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536 Background: The primary tolerability concern with neratinib (NERLYNX®; N), an irreversible pan-HER tyrosine kinase inhibitor, is diarrhea. Data from the multi-cohort, open-label, phase 2 CONTROL trial [Barcenas et al. Ann Oncol 2020] demonstrated significant improvement in grade 3 diarrhea and diarrhea-related discontinuations vs the ExteNET trial, which did not mandate anti-diarrheal prophylaxis. We report a systematic analysis of tolerability in CONTROL and ExteNET. Methods: Patients (pts) ≥18y with stage I–IIIc HER2+ breast cancer received N (240 mg/d po for 1y) after trastuzumab-based adjuvant therapy and were enrolled sequentially into cohorts assessing different modalities to mitigate diarrhea. Cohorts with complete data were included: loperamide (L); L+budesonide (BL); L+colestipol (CL); CL as needed (CL-PRN); and N dose escalation (DE; 120 mg/d on d1–7, 160 mg/d on d8–14, and 240 mg/d thereafter). Integrated ranking (IR) analysis was performed on 13 endpoints in 4 domains (exposure, diarrhea, adverse events [AEs], quality of life [QoL]) identified with input from clinicians; cohorts were ranked from 1 (best) to 5 (worst). Index scores (IS) based on individual pt data from CONTROL were calculated as supportive analysis to confirm selection of the regimen with best overall tolerability, which was then compared with ExteNET. Results: Of the 5 CONTROL cohorts evaluated, DE ranked best for most endpoints. Average ranks per IR method: L 3.4; BL 3.2; CL 3.0; CL-PRN 3.3; DE 2.0. The IS analysis supported DE as the cohort with best overall tolerability. Comparison of CONTROL DE vs ExteNET showed improvement in tolerability in all domains (table). Conclusions: These analyses suggest superiority of weekly DE vs other anti-diarrheal strategies. A lower rate of grade 3 diarrhea was observed with CONTROL DE vs ExteNET (13.3 vs 39.9%, respectively), as well as a comparable or improved AE profile. The data also reveal greater compliance with N (fewer early discontinuations, longer treatment duration, higher cumulative dose) and reduced impact on QoL with DE, suggesting improved tolerability. Clinical trial information: NCT02400476. [Table: see text]

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Negsso, Abebe, Balew Arega, Fekadu Abdissa, Brook Zewdu, Ayele Teshome, Abrham Minda e Asnake Agunie. "Effect of COVID-19 pandemic on the incidence of acute diarrheal disease and pneumonia among under 5 children in Ethiopia- A database study". PLOS Global Public Health 3, n. 6 (14 giugno 2023): e0000304. http://dx.doi.org/10.1371/journal.pgph.0000304.

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COVID-19 has had a devastating impact on preventable and treatable pediatric diseases in Ethiopia. This study looks at the impact of COVID-19 on pneumonia and acute diarrheal diseases in the country, as well as the differences between administrative regions. In Ethiopia, we conducted a retrospective pre-post study to assess the impact of COVID-19 on children under the age of five who had acute diarrhea and pneumonia and were treated in health facilities during the pre-COVID-19 era (March 2019 to February 2020) and the COVID-19 era (March 2020 to February 2021). From the National Health Management District Health Information System (DHIS2, HMIS), we retrieved data on total acute diarrheal disease and pneumonia, along with their regional and monthly distribution. We calculated incidence rate ratios comparing the rates of acute diarrhea and pneumonia during the pre-and post-COVID-19 eras and adjusted for the year, using Poisson regression. The number of under-five children treated for acute pneumonia decreased from 2,448,882 before COVID-19 to 2,089,542 ((14.7% reduction (95%CI;8.72–21.28), p<0.001)) during COVID-19. Similarly, the number of under-five children treated for acute diarrheal disease decreased from 3,287,850 in pre-COVID-19 to, 2,961,771((9.91% reduction (95%CI;6.3–17.6%),p<0.001)) during COVID-19. In the majority of the administrative regions studied, pneumonia and acute diarrhea diseases decreased during COVID-19, but they increased in Gambella, Somalia, and Afar. During the COVID-19 period, the greatest reduction of children with pneumonia (54%) and diarrhea disease (37.3%) was found in Addis Ababa (p<0.001). The majority of administrative regions included in this study have seen a decrease in pneumonia and acute diarrheal diseases among children under the age of five, while three regions namely, Somalia, Gambela, and Afar saw an increase in cases during the pandemic. This emphasizes the importance of using tailored approaches in mitigating the impact of infectious diseases such as diarrhea and pneumonia during situations of a pandemic such as COVID-19.

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Obala, T., S. O. Arojjo, M. Afayoa, K. Ikwap e J. Erume. "The role of Escherichia coli in the etiology of piglet diarrhea in selected pig producing districts of central Uganda". African Journal of Clinical and Experimental Microbiology 22, n. 4 (27 settembre 2021): 515–25. http://dx.doi.org/10.4314/ajcem.v22i4.12.

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Background: Pig production in Uganda is highly constrained by rampant piglet mortalities with diarrhea being a key feature. The present study was conducted to determine possible involvement of Escherichia coli (E. coli) as agents of diarrhea in piglets and elucidate the factors for their spread and virulence, towards development of mitigation strategies in the smallholder pig value chains in Uganda. Methodology: This was a cross-sectional study carried out from January to August 2020 on pre- and post-weaned piglets from households in Kayunga and Mityana districts of Central Uganda, selected by snowballing method to redundancy. Data about herd management and risk factors for colibacillosis were collected from selected farmers in the two districts. A total of 179 faecal samples were collected from randomly selected neonatal and pre-weaning piglets for bacteriological isolation of Escherichia coli. Virulence (enterotoxin and fimbrial) genes from the isolates were detected by multiplex polymerase chain reaction (PCR) assay. Results: From the 179 faecal samples, a total of 158 (88.3%) E. coli isolates were obtained. Virulence gene markers were detected in 18.4% (29/158) of the isolates. Among the investigated genes encoding for enterotoxin production, STb was the most prevalent (16/158, 10.13%), followed by STa (12/158, 7.59%), while gene for LT was not detected. The gene coding for F4 adhesin was the only one detected while F18 adhesin was not detected from the isolates. On multiple logistic regression analysis, only tertiary educational level (OR=0.141; 95% CI=0.30-0.666; p=0.013) and infrequent use of antibiotics (OR=0.231, 95% CI=0.062-0.859; p=0.029) among the farmers, were the two factors significantly protective of the piglets from diarrhoea. Conclusion: This study reports a high prevalence of enterotoxin gene markers among E. coli isolates in piglets and revealed the potential role of these bacteria in the aetiology of piglet diarrhoea and mortalities in Uganda. Additionally, this study identified risk factors that can be useful in formulating treatment and control strategies of infection caused by these bacteria. Further studies are needed to identify more adhesins these E. coli isolates employ for intestinal colonization, a step that will help inform vaccine development. French title: Le rôle d'Escherichia coli dans l'étiologie de la diarrhée des porcelets dans certains districts producteurs de porcs du centre de l'Ouganda Contexte: La production porcine en Ouganda est fortement limitée par la mortalité généralisée des porcelets, la diarrhée étant une caractéristique clé. La présente étude a été menée pour déterminer l'implication possible Escherichia coli piglet diarrhea in Uganda d'Escherichia coli (E. coli) en tant qu'agents de diarrhée chez les porcelets et élucider les facteurs de leur propagation et de leur virulence, vers le développement de stratégies d'atténuation dans les chaînes de valeur des petits producteurs de porcs en Ouganda. Méthodologie: Il s'agit d'une étude transversale réalisée de janvier à août 2020 sur des porcelets pré- et post-sevrés issus de ménages des districts de Kayunga et Mityana du centre de l'Ouganda, sélectionnés par la méthode boule de neige jusqu'à la redondance. Les données sur la gestion du troupeau et les facteurs de risque de colibacillose ont été recueillies auprès d'éleveurs sélectionnés dans les deux districts. Au total, 179 échantillons de matières fécales ont été prélevés sur des porcelets néonatals et en pré-sevrage sélectionnés au hasard pour l'isolement bactériologique d'Escherichia coli. Les gènes de virulence (entérotoxine et fimbrial) des isolats ont été détectés par une amplification en chaîne par polymérase (PCR) multiplex. Résultats: À partir des 179 échantillons de matières fécales, un total de 158 (88,3%) isolats d'E. coli ont été obtenus. Des marqueurs du gène de virulence ont été détectés dans 18,4% (29/158) des isolats. Parmi les gènes étudiés codant pour la production d'entérotoxines, STb était le plus répandu (16/158, 10,13%), suivi de STa (12/158, 7,59%), tandis que le gène de la LT n'a pas été détecté. Le gène codant pour l'adhésine F4 était le seul détecté alors que l'adhésine F18 n'a pas été détectée dans les isolats. Sur l'analyse de régression logistique multiple, seul le niveau d'enseignement supérieur (OR=0,141; IC à 95%=0,30-0,666; p=0,013) et l'utilisation peu fréquente d'antibiotiques (OR=0,231, IC à 95 %=0,062-0,859; p=0,029) parmi les éleveurs, étaient les deux facteurs de protection significative des porcelets contre la diarrhée. Conclusion: Cette étude rapporte une prévalence élevée de marqueurs génétiques d'entérotoxines parmi les isolats d'E. coli chez les porcelets et a révélé le rôle potentiel de ces bactéries dans l'étiologie de la diarrhée et de la mortalité des porcelets en Ouganda. De plus, cette étude a identifié des facteurs de risque qui peuvent être utiles dans la formulation de stratégies de traitement et de contrôle de l'infection causée par ces bactéries. D'autres études sont nécessaires pour identifier plus d'adhésines que ces isolats d'E. coli utilisent pour la colonisation intestinale, une étape qui aidera à éclairer le développement de vaccins.

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Elijah, Catherine, G. E. Nichols, J. T. Gebhardt, Cassandra K. Jones, Jason C. Woodworth, S. S. K. Dritz, J. Bai et al. "PSVI-7 Evaluation of Feed Mitigant Efficacy for Control of Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus When Inoculated Either Alone or Together". Journal of Animal Science 99, Supplement_1 (1 maggio 2021): 217–18. http://dx.doi.org/10.1093/jas/skab054.356.

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Abstract Research has demonstrated that swine feed can be a fomite for viral transmission and certain feed additives can effectively reduce viral contamination. However, additional information is needed to evaluate the efficacy of additives when feed is inoculated with more than one virus. The objective of this study was to evaluate the efficacy of two feed additives for mitigation of porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV) when inoculated individually or together. Feed additives included: 1) no treatment, 2) 0.33% commercial formaldehyde-based product (Sal Curb, Kemin Industries, Des Moines, IA), and 3) 0.50% medium chain fatty acids blend (MCFA; 1:1:1 ratio of C6:C8:C10, Sigma Aldrich, St. Louis, MO). Samples were inoculated with PEDV and PRRSV alone or together at an inoculation concentration of 106 TCID50/g for all viruses. Once inoculated, feed was stored at ambient temperature for 24-h before analyzed via qRT-PCR. For samples inoculated with PEDV or PRRSV alone, a qRT-PCR assay was used which was designed to detect PEDV or PRRSV nucleic acid. For co-inoculated samples, an assay was designed to independently detect both PEDV and PRRSV within a single reaction. For PEDV alone, there was marginally significant evidence that feed additives resulted in differences in cycle threshold (Ct) value (P = 0.052), but no evidence was observed for pairwise differences. For PRRSV alone, formaldehyde increased Ct compared to the untreated control and MCFA treatment (P < 0.05). For co-infection of PRRSV and PEDV, MCFA and formaldehyde increased Ct (P < 0.05) in comparison to non-treated feed. In summary, formaldehyde increased Ct values in feed when contaminated with PRRSV while both mitigants increased Ct value in feed when co-inoculated with PRRSV and PEDV.

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Neupane, Karun, Hamid Ehsan, Ahsan Wahab, Adeel Masood, Tehniat Faraz Ahmed, Saman Bahram, Abdul Hannan et al. "Profile and management of toxicity of selinexor and belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma: A systematic review." Journal of Clinical Oncology 39, n. 15_suppl (20 maggio 2021): e20014-e20014. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e20014.

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e20014 Background: Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of relapsed/refractory multiple myeloma on July 2019 and August 2020 respectively. The toxicity profile of these drugs is a concern since these are approved for use in patients who have already undergone multiple lines of treatment. Methods: Six studies for Sel and two for belamaf were included after a systematic search of PubMed, Embase, Cochrane, and Clinicaltrials.gov. Results: The most common hematological toxicity associated with these two drugs is thrombocytopenia. The common G-3/4 hematological AEs of Sel were thrombocytopenia (39%-71%), anemia (16%-33%), leukopenia (8%-33%) and neutropenia (9%-33%) whereas common G-3/4 non-hematological AEs were hyponatremia (5%-26%), fatigue (13%-15%), diarrhea (5%-10%), eye disorders (9%-10%), musculoskeletal disorders (4%-10%), elevated liver enzymes (10%), peripheral neuropathy (5%) and vomiting (2-4%). Keratopathy and anemia were the major toxicities of belamaf. Most of these toxicities are manageable. Treatment modifications and dose interruption are usually needed when AEs are more than grade II. REMS program guidelines is recommended for close monitoring and evaluation of Sel and belamaf toxicities and early ophthalmological intervention. Conclusions: As these are newer drugs with limited data, continuous surveillance and monitoring is warranted during the treatment course with early mitigation strategies. The physician should be aware of thrombocytopenia and its management as well as belamaf ocular toxicity which is manageable but if missed could have serious complications.[Table: see text]

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Sharma, Pooja, Richa Shri, Fidele Ntie-Kang e Suresh Kumar. "Phytochemical and Ethnopharmacological Perspectives of Ehretia laevis". Molecules 26, n. 12 (8 giugno 2021): 3489. http://dx.doi.org/10.3390/molecules26123489.

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Ehretia laevis Roxb. (Boraginaceae) has been extensively used as a traditional remedy for the treatment of a diverse range of ailments related to the respiratory system, the gastrointestinal tract, the reproductive system, and against several infections. This review critically assesses and documents, for the first time, the fragmented information on E. laevis, including its botanical description, folklore uses, bioactive phyto metabolites and pharmacological activities. The goal is to explore this plant therapeutically. Ethnomedicinal surveys reveal that E. laevis has been used by tribal communities in Asian countries for the treatment of various disorders. Quantitative and qualitative phytochemical investigations of E. laevis showed the presence of important phytoconstituents such as pentacyclic triterpenoids, phenolic acids, flavonoids, fatty acids, steroids, alkaloids, aliphatic alcohols, hydrocarbons, amino acids, carbohydrates, vitamins and minerals. Fresh plant parts, crude extracts, fractions and isolated compounds have been reported to exhibit broad spectrum of therapeutic activities viz., antioxidant, antiarthritic, antidiabetic, anti-inflammatory, antiulcer, antidiarrheal, antidysenteric, wound healing and anti-infective activities. E. laevis is shown to be an excellent potential source of drugs for the mitigation of jaundice, asthma, dysentery, ulcers, diarrhea, ringworm, eczema, diabetes, fissure, syphilis, cuts and wounds, inflammation, liver problems, venereal and infectious disorders. Although few investigations authenticated its traditional uses but employed uncharacterized crude extracts of the plant, the major concerns raised are reproducibility of therapeutic efficacy and safety of plant material. The outcomes of limited pharmacological screening and reported bioactive compounds of E. laevis suggest that there is an urgent need for in-depth pharmacological investigations of the plant.

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Merrill, Scott C., Christopher Koliba, Gabriela Bucini, Eric Clark, Luke Trinity, Asim Zia, Nicholas Cheney et al. "307 A systems approach to understanding biosecurity decision-making". Journal of Animal Science 98, Supplement_4 (3 novembre 2020): 43. http://dx.doi.org/10.1093/jas/skaa278.078.

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Abstract Disease and its consequences result in social and economic impacts to the US animal livestock industry, ranging from losses in human capital to economic costs in excess of a billion dollars annually. Impacts would dramatically escalate if a devastating disease like Foot and Mouth Disease or African Swine Fever virus were to emerge in the United States. Investing in preventative biosecurity can reduce the likelihood of disease incursions and their negative impact on our livestock industry, yet uncertainty persists with regards to developing an effective biosecurity structure and culture. Here we show the implications of human behavior and decision making for biosecurity effectiveness, from the operational level to the owner/managerial level and finally to the systems level. For example, adjustments to risk messaging strategies could double worker compliance with biosecurity practices at the operational level. The improvement of our risk communication strategy may increase willingness to invest in biosecurity. Furthermore, the adaptation of policies could nudge behavior so that we observe a short disease outbreak followed by a quick eradication instead of a pandemic. Our research shows how the emergence of now-endemic diseases, such as Porcine Epidemic Diarrhea virus, cannot be adequately modeled without the use of a human behavioral component. Focusing solely on any one sector or level of the livestock system is not sufficient to predict emergent disease patterns and their social and economic impact on livestock industries. These results provide insight toward developing more effective risk mitigation strategies and ways to nudge behavior toward more disease resilient systems.

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Vargas, Nuria, e Víctor Magaña. "Warm Spells and Climate Risk to Human Health in the Mexico City Metropolitan Area". Weather, Climate, and Society 12, n. 3 (1 luglio 2020): 351–65. http://dx.doi.org/10.1175/wcas-d-19-0096.1.

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AbstractDuring the second half of the twentieth century, rapid demographic growth and urban expansion led to the development of the Mexico City metropolitan area (MCMA) urban heat island (UHI). The thermal gradient between rural and urban regions is used to define the UHI in the transition zone along the 26°C isotherm of mean maximum temperature. As the MCMA expands, more natural vegetation is replaced with urbanization, and the spatial extent of the 26°C isotherm grows. The loss of natural vegetation, in a densely populated region of Mexico, leads to the formation of a canopy-layer UHI. The intensification of the MCMA UHI results in an increase in the frequency of daily maximum temperatures above 30°C (above 26°C on a weekly average), a threshold value that constitutes a natural hazard. Warm-spell occurrences are related to an increase in the number of acute diarrhea diseases (ADD), mainly in zones of the MCMA where the socioeconomic and environmental conditions are low (e.g., insufficient access to potable water). Vulnerable people are mostly located in new settlements along the periphery of the MCMA, where large numbers of hospital discharges due to ADD are reported. The combined effect of more frequent warm spells and increasing vulnerability results in higher levels of risk of suffering this type of health problem, mainly during the warmest part of the year. This analysis may serve to develop UHI mitigation strategies and early warning systems to manage high levels of ADD risk during warm spells.

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Deol, Pallavi, Sukdeb Nandi, Vishal Chander, Chandan Prakash, Sonalika Mahajan, Safoora Kashafi, Ashwini R. Chaple, Saima M. Ganie, Karam Pal Singh e Gaurav Kumar Sharma. "Development of Freeze-dried Reagents based Multiplex PCR Assay for the Detection of Common and Emerging Abortion-causing Pathogens". Journal of Pure and Applied Microbiology 15, n. 3 (16 luglio 2021): 1371–78. http://dx.doi.org/10.22207/jpam.15.3.27.

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Bovine abortion is economically one of the most devastating problems faced by dairy farmers. Apart from non-infectious causes, several infectious pathogens are responsible for abortions, which sometimes manifests as abortion storms. Vaccine against several pathogens is available, in spite of that, abortions cause huge economic losses for the dairy sector. Timely and accurate identification of the etiological agent helps in adopting the mitigation steps to control the damage caused. In addition to the common abortion-causing pathogens such as Brucella abortus, Bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), several emerging viral causes are being investigated for their possible role in abortion, either exclusively or as co-infection. Molecular methods are widely accepted for the identification of the involved pathogens. However, these assays require individual screening against each pathogen which is time-consuming and uneconomical, hence the multiplex format of PCR assays has been adopted by several laboratories. Multiplexing in real-time PCR is a sensitive and reliable technique, but it requires trained manpower and sophisticated equipment which is largely unavailable in regional disease diagnostic laboratories in India. Hence, in this study, a user-friendly, ready-to-use, gel-based RT-PCR multiplex assay was developed for simultaneous detection of three common pathogens (B. abortus, BHV-1, and BVDV) and two emerging pathogens; bluetongue virus (BTV) as a cause of abortions in bovine and Schmallenberg virus (SBV). After the standardization of the assay, a panel of 211 samples was screened. A high degree of concordance was observed which indicates the developed multiplex PCR assay is reliable and has the potential for screening at regional diagnostic laboratories.

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Diallo, Mamadou B. C., Alfredo J. Anceno, Benjawan Tawatsupa, Nitin K. Tripathi, Voranuch Wangsuphachart e Oleg V. Shipin. "GIS-based analysis of the fate of waste-related pathogens Cryptosporidium parvum, Giardia lamblia and Escherichia coli in a tropical canal network". Journal of Water and Health 7, n. 1 (1 ottobre 2008): 133–43. http://dx.doi.org/10.2166/wh.2009.010.

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Urban canals play a major socio-economic role in many tropical countries and, particularly, Thailand. One of the overlooked functions that they perform is a significant attenuation of waste-related pathogens posing considerable health risk, as well as pollution attenuation in general. The study dealt with a comparison of three canals receiving: (i) municipal, (ii) mainly industrial and (iii) mainly agricultural wastewater, listed in order of progressively decreasing organic loading. The occurrence and fate of waterborne Cryptosporidium parvum, Giardia lamblia and Escherichia coli were monitored in the canals by both real-time PCR and conventionally for 12 months. The pathogens are etiological agents of an estimated 38% and 47% of diarrhea cases worldwide and in Thailand, respectively. The geographic information system (GIS) was used to evaluate and map point and, particularly, non-point pollution sources which allowed differentiating the canal sections in terms of predominant pathogen sources. The flowthrough canals, which can be viewed as waste stabilization ponds, were found to be efficiently removing the pathogens at the following generalized specific rates: 0.3 (C. parvum), 1.2 (G. lamblia), 1.8 (E. coli) log10/km.d in the dry season. The rates decreased in the rainy season for E. coli and G. lamblia, but increased for C. parvum which indicated different removal mechanisms. Data suggest that E. coli and G. lamblia were mainly removed through sedimentation and sunlight (UV) irradiation, while the likely mechanism for C. parvum was predation. Overall, the specific pathogen removal rates positively correlated with the canal organic loading rates in the rainy season. As an important result, an estimate of the municipal pollution mitigation by over 2,280 km canals in the Greater Bangkok suggests that concomitant to the pathogens at least 36–95 tons of BOD5 is being removed daily, thereby saving the receiving Chao Phraya River and Bight of Bangkok, by far exceeding current, from major eutrophication problems.

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Blomme, Allison K., Jordan T. Gebhardt, Cassandra K. Jones, Jason C. Woodworth, Elizabeth Poulsen-Porter, Jianfa Bai, Jon R. Bergstrom e Chad B. Paulk. "PSV-5 Effects of Benzoic Acid and an Essential Oils Blend on Detection of Swine Viruses in Inoculated Swine Feed and Premix". Journal of Animal Science 100, Supplement_2 (12 aprile 2022): 193–94. http://dx.doi.org/10.1093/jas/skac064.326.

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Abstract Feed has been shown to harbor viable viruses over an extended period. This study investigated the use of benzoic acid (BA) and an essential oils blend (EO) to mitigate the presence of porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and Senecavirus A (SVA) in a complete diet (Exp. 1) and a vitamin premix (Exp. 2). Experiment 1 consisted of a control with no additive, 0.5% BA, 0.5% BA and 200 ppm EO, 0.3% BA and 120 ppm EO, and 0.25% BA and 100 ppm EO. Feed samples were inoculated with PEDV, PRRSV, and SVA. For Exp. 2, the control contained no additive, and treatment had 2.68% EO included to mitigate PEDV. Inoculated feed or premix was stored at room temperature with sampling points at 2, 5, and 15 d post-inoculation (dpi). Samples were analyzed using triplex qRT-PCR to detect changes in RNA quantities for all viruses. Detectible PRRSV in the feed demonstrated a quadratic decrease over time (P = 0.038). A significant treatment × day interaction was observed in the feed for both PEDV (P = 0.008) and SVA (P < 0.001). The 0.5% BA treatment had greater (P < 0.05) amounts of detectible PEDV on d 2 and 5 and decreased detectible PEDV on d 15 compared with control. The 0.5% BA treated feed demonstrated decreased (P < 0.05) detectable SVA at 2 dpi but greater detectible SVA at 15 dpi compared with control. Both PEDV and SVA demonstrated viral degradation over time. The use of the EO in the vitamin premix had no evidence of main or interactive effects. In conclusion, 0.5% BA decreased PEDV at 15 dpi, but BA and EO mitigation in this model did not provide consistent evidence for increased viral degradation. However, time decreased detectability of all three viruses.

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Carter, Scott D., Kitty Cardwell, Andres Espindola Camacho e Ishtar Silva Lara. "91 Electronic probes for assessment of changes in gastrointestinal microbiome in nursery pigs". Journal of Animal Science 98, Supplement_3 (2 novembre 2020): 25–26. http://dx.doi.org/10.1093/jas/skaa054.045.

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Abstract Gut microbiota play an important role in extraction, synthesis and absorption of nutrients. Commensal bacteria prevent pathogenic bacteria colonization and maintain intestinal epithelium integrity. The most common families of commensal bacteria in nursery pigs are Prevotellaceae, Clostridiaceae, Erysipelotrichaceae, Lachnospitaceae, Lactobacillaceae, Ruminicoccaceae and Streptoccocaceae. Understanding the microbial abundance shifts that causes health disruption leading to diarrhea and stunted growth performance can be of great benefit for developing mitigation strategies. Next generation sequencing (NGS) technology facilitates metagenomic approaches, developing sequencing profile representing any and all organisms within a sample. Electronic-probe Diagnostic Nucleic acid Analysis (EDNA) is a bioinformatic tool originally developed to detect species-specific plant pathogen targets in metagenomic databases. EDNA has been shown to reduce time to detect microbial signatures in large metagenomic sequence data. However, it has not previously been used as a metagenomic tool for assessing microbiome composition at the family level. Therefore, a metagenomic sequencing based in silico detection of gut microbiota using E-probes of the seven most common commensal families was developed and further validated in vitro. E-probes were designed from the selected families as follows, Prevotellaceae (89,565), Clostridiaceae (58,554), Erysipelotrichaceae (195), Lachnospitaceae (87), Lactobacillaceae (211,507), Ruminicoccaceae (14,575) and Streptoccocaceae (54,632). Fecal metagenomes of nursery pigs from 0, 7, 14, and 21 d were used to validate the E-probes. The hits were able to detect the relative abundance variations of the 4-time periods. The results between hits and reads were as follows, Prevotellaceae (r2 = 0.98), Clostridiaceae (r2 = 0.99), Erysipelotrichaceae (r2 = 0.99), Lachnospitaceae (r2 = 0.99), Lactobacillaceae (r2 = 0.91), Ruminicoccaceae (r2 = 0.99) and Streptoccocaceae (r2 = 0.98). These results validate in silico usage of E-probes to detect the relative abundance variations in gut microbiota. Further in vitro validation will be performed to assess the microbial changes related to diet in nursery pigs.

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Woodworth, Jason C., Jordan T. Gebhardt, Cassandra K. Jones, Chad B. Paulk, S. S. Dritz, Mike D. Tokach, Robert D. Goodband e Joel M. DeRouchey. "305 Awardee Talk: Transferring a culture of biosecurity to the feedmill". Journal of Animal Science 98, Supplement_4 (3 novembre 2020): 42. http://dx.doi.org/10.1093/jas/skaa278.076.

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Abstract A culture of on-farm biosecurity has been established and practiced by modern swine production systems for many years. The value of this has been repeatedly demonstrated through improved animal health and performance based on the prevention of disease introduction to the herd. With the introduction of Porcine Epidemic Diarrhea Virus (PEDV) to the US swine industry in 2013, we have learned that feed and feed ingredients can be vectors of disease transmission. Therefore, there is a heightened need to transfer our on-farm biosecurity culture to our feedmills and entire feed supply chain as a way to help prevent disease introduction into swine farms. Feedmills are designed to efficiently and effectively blend feed components into a homogenous batch, and the potential to distribute contaminated feed to multiple farms is significant. While feed and ingredients can be vectors of disease and pathogen transmission, our data continues to show that people are a major risk for pathogen transmission throughout the feed supply chain. Key biosecurity principles such as exclusion, prevention, isolation, mitigation, disinfection, and containment should be adopted and enforced for a strong feedmill biosecurity program. A written feedmill biosecurity plan should be developed and a training program that covers all employees as well as visitors and delivery drivers should be implemented. Continuous risk assessment and environmental monitoring should be utilized to identify new areas of risk and to assess the current status. Unfortunately, feedmills are nearly impossible to completely disinfect and therefore every effort should be made to prevent the introduction of pathogens into the mill. Research that we have conducted with PEDV and African Swine Fever Virus has demonstrated that adopting a culture of biosecurity at the feedmill will reduce risk of disease and pathogen exposure on farms.

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Mcconnico, R. S., e C. B. Navarre. "(P2-33) Biosecurity Considerations for Equine Emergency Sheltering". Prehospital and Disaster Medicine 26, S1 (maggio 2011): s146. http://dx.doi.org/10.1017/s1049023x11004778.

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Equine emergency shelters have an increased risk of infectious disease occurrences due to increased animal stress levels, excessive co-mingling, inconsistent worker base, and horses arriving from many and varied health management and stabling situations. Biosecurity policies should be in place ahead of time to prevent disease spread and outbreak situations and policies should be effectively conveyed to all shelter personnel. A veterinarian should be involved in the overall health management of an equine emergency shelter including working with public health officials regarding the overall animal and human safety issues associated with effectively managing an equine shelter. The veterinarian should work closely with the shelter manager and both need to be able to apply Incident Command System and National Incident Management Systems applications to maximize disease prevention. Mitigation tactics should include appropriate regular equine health maintenance including current vaccinations against tetanus, Equine Influenza I & II, Equine Herpes virus I & IV, and the encephalitides including Eastern, Western, and West Nile Viruses as part of horse owner emergency preparedness planning. Equine Infectious Anemia (EIA) is a federally regulated equine disease and during disaster situations it is unrealistic to assume that all horses will have a record of a current negative test. EIA testing should be considered a part of the plan for shelter animals depending on risk assessments. Appropriate personal hygiene, particularly hand hygiene, can assist in the prevention of disease transmission. Separate isolation areas are necessary for horses showing clinical signs of infectious disease including fever, nasal discharge, or diarrhea. Equine emergency shelter husbandry plans should include a plan for safe handling of feedstuffs, and water. An effective and implementable biosecurity plan for equine emergency sheltering is a key critical requirement for successful large animal emergency and disaster response outcome.

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Gebhardt, J. T., J. C. Woodworth, C. K. Jones, M. D. Tokach, J. M. DeRouchey, R. D. Goodband, J. R. Bergstrom et al. "100 Evaluating the efficacy of commercial feed additives as potential porcine epidemic diarrhea virus (PEDV) mitigation strategies in complete feed and spray-dried porcine plasma as determined by polymerase chain reaction analysis and bioassay". Journal of Animal Science 95, suppl_2 (1 marzo 2017): 47. http://dx.doi.org/10.2527/asasmw.2017.100.

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41

McChalicher, Christopher, Ahmad Abdulaziz, Elizabeth Halvorsen, Mary-Jane Lombardo, Jonathan Winkler, Sanabel Almomani, Barbara McGovern, Gregory McKenzie, David Ege e John Aunins. "1035. Manufacturing Processes of SER-109, a Purified Investigational Microbiome Therapeutic, Reduce Risk of Transmission of Emerging and Undetected Infections in Donor Stool". Open Forum Infectious Diseases 8, Supplement_1 (1 novembre 2021): S607—S608. http://dx.doi.org/10.1093/ofid/ofab466.1229.

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Abstract Background Fecal microbiota transplantation (FMT) is vulnerable to emerging pathogens due to reliance on donor screening for risk mitigation. These concerns were highlighted by dual FDA safety alerts regarding FMT transmission of bacterial pathogens, which were recognized in hindsight only after hospitalizations and deaths. The FDA also warned of potential risk of SARS-CoV-2 transmission, leading to quarantine of FMT in March 2020, two months after COVID-19 was reported on US soil. Conversely, our development program for SER-109, an oral investigational microbiome therapeutic, was prospectively designed to inactivate organisms of concern, while purifying the hardy Firmicutes spores. We evaluated whether the manufacturing processes for SER-109 inactivate model organisms, including a coronavirus with gastrointestinal tropism, and a representative Gram-negative bacterium. Methods Model organisms were selected based on biologic suitability, detectability, and laboratory safety. Porcine Epidemic Diarrhea Virus (PEDV, a coronavirus) was selected to model SARS-CoV-2. Quantitation used a Vero cell tissue culture infectious dose (TCID50) assay. For E. coli, a rifampicin-tolerant Salmonella enterica was selected and quantified with MacConkey lactose agar plus rifampicin. Spiking experiments into representative fecal suspensions were completed to measure inactivation of model organisms. Log-reduction factors (LRF) were calculated based on the drop in organism titer during inactivation. Hold controls in non-ethanolic test matrices were used to confirm specificity of the ethanol inactivation. Results In 70% v/v ethanol, PEDV was inactivated by more than 4.2 log10 (to limit of detection, LOD) within 4 minutes (Fig1). In 50% v/v ethanol, S. enterica was inactivated by more than 6.5 log10 (to LOD) within 30 seconds (Fig2). Figure 1. Inactivation of Porcine Epidemic Diarrhea Virus (PEDV), log10 reduction factor (LRF) versus time Average of two experiments shown. Also shown is the maximum achievable inactivation based on the limit of detection (LOD). Figure 2. Inactivation of S. enterica, log10 reduction factor (LRF) versus time. Average of three experiments with error bars represent 95% CI. Also shown is the maximum achievable inactivation based on the limit of detection (LOD). Conclusion These experiments demonstrate substantial inactivation of the model organisms and support the potential benefit of SER-109 manufacturing process to mitigate risks of undetected or emerging pathogens for which reliable screening is limited. Ethanol exposure leads to a purified investigational product of beneficial Firmicutes spores while affording a safety net beyond donor screening alone. Disclosures Christopher McChalicher, n/a, Seres Therapeutics (Employee, Shareholder) Ahmad Abdulaziz, MS, Seres Therapeutics Inc. (Employee, Shareholder) Elizabeth Halvorsen, PhD, Seres Therapeutics (Employee, Shareholder) Mary-Jane Lombardo, PhD, Seres Therapeutics (Employee, Shareholder) Jonathan Winkler, PhD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Gregory McKenzie, PhD, Prolacta Bioscience (Employee) David Ege, PhD, Merck & Co., Inc. (Shareholder)Seres Therapeutics (Employee, Shareholder) John Aunins, PhD, Seres Therapeutics, Inc. (Employee)

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Manley, Morgan, Tahaniyat Lalani, Kalyani Telu, David Tribble, Drake H. Tilley, Anuradha Ganesan, Anjali Kunz et al. "741. TravMil Surveillance of Travel-Related Illness in a Prospective Cohort of US Military Beneficiaries, 2010–2018". Open Forum Infectious Diseases 6, Supplement_2 (ottobre 2019): S331. http://dx.doi.org/10.1093/ofid/ofz360.809.

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Abstract Background Increasing international travel places larger populations at risk for infections outside of their usual exposure. Deployed military personnel have unique risks for such infections. Our cohort’s rates of travelers’ diarrhea and influenza-like illness have been defined, but the rate of travelers with symptoms apart from a clinical syndrome has not. We present a survey of intra-travel symptoms of all travelers and confirmed diagnoses of ill-returned travelers in a cohort of military and civilian travelers. Methods TravMil is a prospective, multicenter observational study enrolling US military beneficiaries traveling outside the continental United States from 2010–2018; beneficiaries could also enroll after travel if they presented for a possible travel-related illness. Demographic information, intra-travel symptoms, and confirmed diagnoses were recorded. Results 2671 travelers embarked on 3050 trips: 63.1% male; median age 38 years (IQR 27, 57); median trip duration 20 days (IQR 13, 46). Common purposes of travel: military deployment (45.9%), vacation (23.7%), and visiting friends/relatives (10.9%). Ninety-seven travelers (3.2%) enrolled post-travel. Top regions of travel: Africa (31.5%), South and Central America/Caribbean (25.5%), and Southeast and North Asia/Oceania (19.4%). During travel, 56.6% experienced gastrointestinal (GI) symptoms, 11.9% respiratory symptoms, and 3.0% fever; of those, 10.3% sought medical care. Eighty returned travelers sought medical care (21 prospective enrollees vs. 59 post-travel enrollees): 5 vs. 17 malaria cases, 3 vs. 16 arbovirus infections, and 6 vs. 14 GI syndromes. All malaria cases in prospective enrollees were in military subjects. Post-travel enrollees accounted for 1 acute human immunodeficiency virus and 3 rickettsial infections. Conclusion A majority of our travelers experienced symptoms during travel. Post-travel diagnoses, although uncommon, emphasize needed improvements in the application of known risk mitigation strategies. Our findings can help clinicians optimize their pretravel counseling by focusing education on self-treatment of common travel-related symptoms, prevention of GI, arthropod-borne, and respiratory illness, and emphasizing symptoms that should prompt medical care. Disclosures All authors: No reported disclosures.

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Theurer, Miles E., Robert L. Larson e Brad J. White. "Systematic review and meta-analysis of the effectiveness of commercially available vaccines against bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus for mitigation of bovine respiratory disease complex in cattle". Journal of the American Veterinary Medical Association 246, n. 1 (gennaio 2015): 126–42. http://dx.doi.org/10.2460/javma.246.1.126.

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Satoi, Sohei, Motoki Miyazawa, Masaji Tani, Manabu Kawai, Seiko Hirono, Ken-Ichi Okada, Hiroaki Yanagimoto et al. "Phase II study of alternate-day oral therapy with S-1 for unresectable advanced pancreatic cancer: An updated report." Journal of Clinical Oncology 31, n. 4_suppl (1 febbraio 2013): 252. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.252.

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252 Background: Based on the results of GEST, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effect. Grade3/4 toxicities (%) in S-1 were neutropenia 8.8, anorexia 11.4, diarrhea 5.5. On the other hand, we experienced in clinical practice that the alternate-day administration of S-1 reduced adverse effects and was tolerable for unresectable advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multi-center cooperative prospective study to compare daily with alternate-day administration of S-1 for unresectable advanced pancreatic cancer. Methods: Patients with unresectable advanced pancreatic cancer (PS, 0 to 1; age, 20 to 80 years; no other therapy) were eligible for enrollment in this trial. S-1 was administered a dose of 40 to 60 mg twice daily, assigned according to body-surface area, on Monday, Wednesday, Friday, and Sunday (specified days). Each treatment cycle will be 42 days (6 weeks). The primary endpoint was overall survival (OS). Secondary endpoints were safety, response rate (RR), progression free survival (PFS), time to treatment failure (TTF). Results: A total of 50 patients were enrolled from Sep 2009 to Feb 2011. 48 patients were evaluable for response. Male/Female was 21/27, PS: 0/1 was 40/8. With a median follow-up time of 28.2 months, OS as primary endpoint was 8.4 months (95% CI, 5.4-10.8) with the 1 year survival rate 29.2%. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4% (95% CI: 3.5-19.1), and Disease Control rate was 79.2%. Grade 3/4 hematological and non-hematological toxicities were minor. All of those adverse reactions were tolerable and reversible. Conclusions: We will report the data from the final analysis at this meeting. The current data show mitigation of adverse effects with alternate-day administration of S-1, and it appears to be a more sustainable option for unresectable advanced pancreatic cancer. A randomized phase II trial comparing this regimen of S-1 with standard regimen of S-1 is ongoing. Clinical trial information: 000003453.

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Richter, Veronika, Elisabeth Kattwinkel, Clair L. Firth, Tatiana Marschik, Marc Dangelmaier, Martine Trauffler, Walter Obritzhauser, Walter Baumgartner, Annemarie Käsbohrer e Beate Pinior. "Mapping the global prevalence of bovine viral diarrhoea virus infection and its associated mitigation programmes". Veterinary Record 184, n. 23 (30 aprile 2019): 711. http://dx.doi.org/10.1136/vr.105354.

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The aim of this study was to collect information on the global distribution of the prevalence of bovine viral diarrhoea virus (BVDV) and respective mitigation programmes, using a questionnaire and literature review to provide as complete a picture of the worldwide BVDV situation as possible. This study collated information on 107 countries with respect to mitigation activities and 88 countries regarding BVDV infections during the observation period (1960–2017). A heterogeneous epidemiological situation for both BVDV prevalence and the presence of mitigation programmes was observed. The results of this analysis could be used to increase the visibility of the distribution of BVDV, to provide supporting data for global animal disease databases and to assist veterinary public health authorities in the decision-making processes to establish mitigation activities.

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Wu, Jianyong, Alexander van Geen, Kazi Matin Ahmed, Yasuyuki Akita Jahangir Alam, Patricia J. Culligan, Veronica Escamilla, John Feighery et al. "Increase in Diarrheal Disease Associated with Arsenic Mitigation in Bangladesh". PLoS ONE 6, n. 12 (28 dicembre 2011): e29593. http://dx.doi.org/10.1371/journal.pone.0029593.

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Cavalcanti, Daniella Medeiros, José Alejandro Ordoñez, Temidayo Aransiola, Cristina Almeida, Juan Felipe Perdomo Díaz, Daniela Zuluaga Mayorga, Alejandro Zamudio Sosa et al. "Evaluation and Forecasting Analysis of the Association of Conditional Cash Transfer With Child Mortality in Latin America, 2000-2030". JAMA Network Open 6, n. 7 (14 luglio 2023): e2323489. http://dx.doi.org/10.1001/jamanetworkopen.2023.23489.

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ImportanceLatin America has implemented the world’s largest and most consolidated conditional cash transfer (CCT) programs during the last 2 decades. As a consequence of the COVID-19 pandemic, poverty rates have markedly increased, and a large number of newly low-income individuals, especially children, have been left unprotected.ObjectiveTo evaluate the association of CCT programs with child health in Latin American countries during the last 2 decades and forecast child mortality trends up to 2030 according to CCT alternative implementation options.Design, Setting, and ParticipantsThis cohort study used a multicountry, longitudinal, ecological design with multivariable negative binomial regression models, which were adjusted for all relevant demographic, socioeconomic, and health care variables, integrating the retrospective impact evaluations from January 1, 2000, to December 31, 2019, with dynamic microsimulation models to forecast potential child mortality scenarios up to 2030. The study cohort included 4882 municipalities from Brazil, Ecuador, and Mexico with adequate quality of civil registration and vital statistics according to a validated multidimensional criterion. Data analysis was performed from September 2022 to February 2023.ExposureConditional cash transfer coverage of the target (lowest-income) population categorized into 4 levels: low (0%-29.9%), intermediate (30.0%-69.9%), high (70.0%-99.9%), and consolidated (≥100%).Main Outcomes and MeasuresThe main outcomes were mortality rates for those younger than 5 years and hospitalization rates (per 1000 live births), overall and by poverty-related causes (diarrheal, malnutrition, tuberculosis, malaria, lower respiratory tract infections, and HIV/AIDS), and the mortality rates for those younger than 5 years by age groups, namely, neonatal (0-28 days), postneonatal (28 days to 1 year), infant (&lt;1 year), and toddler (1-4 years).ResultsThe retrospective analysis included 4882 municipalities. During the study period of January 1, 2000, to December 31, 2019, mortality in Brazil, Ecuador, and Mexico decreased by 7.8% in children and 6.5% in infants, and an increase in coverage of CCT programs of 76.8% was observed in these Latin American countries. Conditional cash transfer programs were associated with significant reductions of mortality rates in those younger than 5 years (rate ratio [RR], 0.76; 95% CI, 0.75-0.76), having prevented 738 919 (95% CI, 695 641-782 104) child deaths during this period. The association of highest coverage of CCT programs was stronger with poverty-related diseases, such as malnutrition (RR, 0.33; 95% CI, 0.31-0.35), diarrhea (RR, 0.41; 95% CI, 0.40-0.43), lower respiratory tract infections (RR, 0.66, 95% CI, 0.65-0.68), malaria (RR, 0.76; 95% CI, 0.63-0.93), tuberculosis (RR, 0.62; 95% CI, 0.48-0.79), and HIV/AIDS (RR, 0.32; 95% CI, 0.28-0.37). Several sensitivity and triangulation analyses confirmed the robustness of the results. Considering a scenario of moderate economic crisis, a mitigation strategy that will increase the coverage of CCTs to protect those newly in poverty could reduce the mortality rate for those younger than 5 years by up to 17% (RR, 0.83; 95% CI, 0.80-0.85) and prevent 153 601 (95% CI, 127 441-180 600) child deaths by 2030 in Brazil, Ecuador, and Mexico.Conclusions and RelevanceThe results of this cohort study suggest that the expansion of CCT programs could strongly reduce childhood hospitalization and mortality in Latin America and should be considered an effective strategy to mitigate the health impact of the current global economic crisis in low- and middle-income countries.

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Gonzalez-Kozlova, Edgar, Diane Del Valle, Kevin Tuballes, Vanessa Barcessat, Stephanie King, Hsin hui Huang, Manishkumar Patel et al. "Serum cytokines and autoantibodies to GM-CSF and immune-related colitis in ipilimumab-treated patients with cancer." Journal of Clinical Oncology 41, n. 16_suppl (1 giugno 2023): 12080. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.12080.

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12080 Background: Despite the demonstrated efficacy of immune checkpoint inhibitors (ICI) including CTLA-4 and PD-(L)1 blockade, serious immune related adverse events including immune-related colitis (irColitis) often limit their use. Understanding the mechanisms that drive irColitis as well as predictive biomarkers is critical to informing the benefit:toxicity ratio of these medications. Methods: We tested serial blood specimens from 63 patients enrolled in six ipilimumab-containing clinical trials to evaluate changes in circulating cytokines and autoantibodies (auAb) to GM-CSF with irColitis occurrence. Retrospective blood specimens were analyzed from 31 patients who developed irColitis and 32 age and sex matched controls. irColitis was defined as either: 1) histologically confirmed colitis or 2) clinically significant diarrhea prompting initiation of corticosteroid therapy. Over a 24-week period, serum samples were collected at baseline, week 6, symptom onset, and post-symptom resolution. Serum proteins were assessed using the Immuno-Oncology and Inflammatory Olink panels. Anti-GM-CSF auAb were measured by enzyme-linked immunosorbent assay. Unsupervised clustering and mixed linear models were used to evaluate the changes associated with irColitis. Demographics, treatments, and technical variables were modeled for controlling artifacts. Significance was defined as Log2FC > 0.5, P < 0.05 and FDR < 0.05 (false discovery rate adjusted p-values) denoted with * and **, respectively. Results: While 69 proteins were significantly dysregulated with ICI treatment, patients who developed irColitis compared to those who did not showed higher levels of CD8A*, CXCL10* at baseline and prior to colitis onset at week 6, and then higher MMP10**, IL17A*-C*, CCL20**, OSM**, among others, at time of colitis and resolution. Further, patients who experienced irColitis showed an increase in anti-GM-CSF IgA** and IgG** Ab titers at Week 6 and at colitis onset compared with baseline, with higher IgA* after irColitis resolution compared to no colitis, while no significant differences were identified at baseline. Conclusions: Indicators of clinical outcomes can be obtained easily and minimally invasively by measuring circulating soluble proteins. Here, we identified differentially expressed cytokines associated with irColitis from retrospective cohorts. These potential biomarkers point to transient dysregulation of gut homeostasis that could help to stratify patients developing irColitis and to consider targeted mitigation strategies. These observations are currently being prospectively investigated. NCI support: Scientific and financial support for the IOTN Network is provided through the National Cancer Institute (NCI) U01DK124165. Institutional Review Board (IRB) STUDY #19-0246. This research was funded in part through the NIH/NCI P30 CA008748.

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Daver, Naval, Daniel A. Pollyea, Karen W. L. Yee, Pierre Fenaux, Joseph M. Brandwein, Norbert Vey, Giovanni Martinelli et al. "Preliminary Results from a Phase Ib Study Evaluating BCL-2 Inhibitor Venetoclax in Combination with MEK Inhibitor Cobimetinib or MDM2 Inhibitor Idasanutlin in Patients with Relapsed or Refractory (R/R) AML". Blood 130, Suppl_1 (7 dicembre 2017): 813. http://dx.doi.org/10.1182/blood.v130.suppl_1.813.813.

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Abstract Introduction: Effective treatment options for patients (pts) with R/R AML are limited and novel therapies are needed. Previous pre-clinical data have shown that venetoclax (VEN) plus cobimetinib (cobi) or idasanutlin (idasa) may be synergistic. MEK and MDM2 inhibition have been shown to down-regulate MCL-1, overcoming a resistance pathway to BCL-2 inhibition in AML (Han, ASH 2016; Pan, ASH 2014). We report preliminary results from a dose-escalation study evaluating VEN plus cobi or idasa in pts with R/R AML. This is the first study evaluating novel-novel oral combinations with VEN in pts with AML. Methods: This open-label, multicenter study evaluates the safety, tolerability and efficacy of VEN + cobi or idasa in pts ≥60 yrs old with R/R or secondary AML who have received therapy for a prior antecedent hematological disease and are not eligible for cytotoxic therapy (NCT02670044). Two-dimensional dose escalation is being used to establish the maximum tolerated dose (MTD) for each combination. Pts on Arm A received VEN PO daily + cobi PO on Days 1-21, and pts on Arm B received VEN PO daily + idasa PO on Days 1-5 in 28-day cycles. Dose limiting toxicities (DLTs) were assessed for the first cycle. Results: As of 25 April 2017, 42 pts were treated in the dose-escalation stage. Arm A included 4 cohorts: VEN 400 mg + cobi 40 mg (n=4), VEN 600 mg + cobi 40 mg (n=7), VEN 800 mg + cobi 40 mg (n=4) and VEN 400 mg + cobi 60 mg (n=7); Arm B included 3 cohorts: VEN 400 mg + idasa 200 mg (n=3), VEN 600 mg + idasa 200 mg (n=8) and VEN 400 mg + idasa 400 mg (n=9). Median age was 72 (range 60-93) yrs and median number of prior therapies was 2 (range 1-10). 19% (8/42) were ECOG 2, 62% (26/42) of pts were refractory to last therapy and 48% (20/42) of pts had secondary AML. According to ELN risk classification, 29% were intermediate-I, 34% intermediate-II and 34% were adverse risk. Most common AEs in both arms are summarized in Table 1. In the VEN + cobi arm, the majority of deaths on study were due to progressive disease (PD); 3 deaths were due to AEs of sepsis, pneumonia and respiratory failure. Three DLTs were reported: 1 diarrhea (Gr 3) in VEN 600 mg + cobi 40 mg and 1 diarrhea (Gr 3) and 1 decrease in ejection fraction (EF) (Gr 3) in VEN 400 mg + cobi 60 mg. The Gr 3 decrease in EF occurred in the setting of sepsis and was subsequently not considered related to study treatment. Due to the higher rates of Gr ≥3 diarrhea (57%) in VEN 400 mg + cobi 60 mg, this dose level will no longer be evaluated in this study. The VEN 800 mg + cobi 40 mg cohort is ongoing. In the VEN + idasa arm, the most common cause of death was PD; 1 death was due to an AE of sepsis. Four DLTs were reported: 1 generalized muscle weakness (Gr 3) and 1 diarrhea (Gr 3) in VEN 600 + idasa 200 mg and 1 acute coronary syndrome (Gr 3) and 1 elevated bilirubin (Gr 4) in VEN 400 mg + idasa 400 mg. Additional dose cohorts evaluating VEN + idasa are ongoing. When compared to monotherapy data at the same dose, preliminary PK analyses suggest that VEN exposure is slightly lower, while cobi and idasa exposures are similar. Preliminary efficacy for the VEN + cobi arm showed 2 CRs (9%), 1 CRp (4.5%) and 1 CRi (4.5%) for an overall response rate (ORR) of 18% (4/22); duration of response (DOR) ranged from 1 to 5 mo, with 1 response ongoing at data cut-off. For the VEN + idasa arm, 1 CR (5%), 1 CRp (5%), 1 CRi (5%) and 1 PR (5%) were achieved for an ORR of 20% (4/20); DOR ranged from 1.3 to 6.7 mo, with 1 response ongoing at data cut-off. In the VEN 600 mg + idasa 200 mg cohort, the ORR was 38% (3/8) with 1 CR, 1 CRp, and 1 CRi. Of the pts who did not achieve a response by IWG criteria, anti-leukemic activity was seen in an additional 7 pts who achieved ≥ 50% bone marrow blast reduction from baseline (3/22 [14%] pts on VEN + cobi and 4/20 [20%] pts on VEN + idasa). Baseline mutation profiling was available in 32 of 42 pts and is summarized for responders in Table 2. Of the 9 pts who had an IDH1/2 mutation at baseline, 44% (4/9) achieved a response (1 on VEN + cobi and 3 on VEN + idasa). Of the 3 pts with known p53 mutations on the VEN + idasa cohorts, none achieved a response. Conclusions: Preliminary results show that VEN plus cobi or idasa can be administered with appropriate risk mitigation measures for GI toxicity and early evidence of clinical activity in R/R AML pts. Dose finding is ongoing and the MTD for both combinations has not yet been determined. Preliminary ORR for the VEN 600 mg + idasa 200 mg cohort was encouraging at 38%. Safety, PK and efficacy data will be updated at the time of presentation. Disclosures Daver: Novartis Pharmaceuticals Corporation: Consultancy; Pfizer Inc.: Consultancy, Research Funding; Otsuka America Pharmaceutical, Inc.: Consultancy; Karyopharm: Consultancy, Research Funding; Incyte Corporation: Honoraria, Research Funding; Bristol-Myers Squibb Company: Consultancy, Research Funding; Daiichi-Sankyo: Research Funding; Jazz: Consultancy; Immunogen: Research Funding; Kiromic: Research Funding; Sunesis Pharmaceuticals, Inc.: Consultancy, Research Funding. Pollyea: Takeda, Ariad, Alexion, Celgene, Pfizer, Pharmacyclics, Gilead, Jazz, Servier, Curis: Membership on an entity's Board of Directors or advisory committees; Agios, Pfizer: Research Funding. Yee: Oncoethix: Research Funding; Novartis Canada: Honoraria; Astex: Research Funding; Karyopharm: Research Funding; Celgene Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux: Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Kelly: Abbvie: Honoraria; Pharmacyclics: Honoraria; Amgen: Honoraria; Jannsen: Honoraria. Roboz: Cellectis: Research Funding; AbbVie, Agios, Amgen, Amphivena, Array Biopharma Inc., Astex, AstraZeneca, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Novartis, Onconova, Pfizer, Roche Pharmace: Consultancy. Kshirsagar: Genentech, Inc: Other: Services via contractor. Dail: Genentech, Inc.: Employment. Wang: Genentech: Employment. Mobasher: Roche: Equity Ownership; Genentech: Employment. Chen: 4. F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Hong: Genentech: Employment; F. Hoffmann-La Roche Ltd: Equity Ownership.

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Gupta, Vikas, Abdulraheem Yacoub, Srdan Verstovsek, Ruben A. Mesa, Claire N. Harrison, Giovanni Barosi, Jean-Jacques Kiladjian et al. "Safety and Tolerability of Fedratinib (FEDR), an Oral Inhibitor of Janus Kinase 2 (JAK2), in Patients with Intermediate- or High-Risk Myelofibrosis (MF) Previously Treated with Ruxolitinib (RUX): Results from the Phase 3b FREEDOM Trial". Blood 138, Supplement 1 (5 novembre 2021): 389. http://dx.doi.org/10.1182/blood-2021-147607.

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Abstract INTRODUCTION: Ruxolitinib (RUX) has demonstrated efficacy in patients (pts) with MF, but many pts discontinue (D/C) RUX due to loss of response or treatment (Tx)-related cytopenias. Fedratinib (FEDR) is an oral, selective JAK2 inhibitor approved for Tx of pts with MF, including those previously treated with RUX. In the single-arm, phase 2 JAKARTA2 trial of FEDR 400 mg/day (d) in pts with MF resistant/intolerant to prior RUX, 31% of pts achieved a spleen volume response and 27% achieved a symptom response with FEDR. The most common adverse events (AEs) in JAKARTA2 were gastrointestinal (GI) events, including diarrhea in 62% of pts, nausea in 56%, and vomiting in 41%. A temporary clinical hold was placed on FEDR in 2013 due to suspected cases of Wernicke's encephalopathy (WE). The ongoing, single-arm, phase 3b FREEDOM trial (NCT03755518) further evaluates the safety and efficacy of FEDR in pts with MF previously treated with RUX. Unlike JAKARTA2 and other early FEDR trials, FREEDOM includes prospective strategies for preventing or mitigating GI AEs, thiamine level decreases, and potential WE. We investigated the safety of FEDR 400 mg/d in FREEDOM, including the effectiveness of these strategies. METHODS: Eligible pts are aged ≥ 18 years with DIPSS-defined intermediate- or high-risk, primary or post-PV/ET MF, ECOG PS ≤ 2, platelet count ≥ 50 ×10 9/L, and spleen volume ≥ 450 cm 3 by MRI/CT or palpable spleen ≥ 5 cm below the left costal margin (LCM). Pts must have previously received RUX for ≥ 3 months (mo), or for ≥ 28d with development of RBC transfusion requirement (≥ 2 units/mo for 2 mo) or grade ≥ 3 thrombocytopenia, anemia, hematoma, or hemorrhage. All pts received FEDR 400 mg QD in continuous 28d cycles. AE mitigation strategies include prophylactic and symptomatic use of anti-nausea/vomiting and anti-diarrheal Tx, thiamine supplementation, FEDR dosing modifications, and administration of FEDR with food. All pts who received ≥ 1 FEDR dose were evaluated for safety. AEs were coded using MedDRA v24.0 and graded (G) by CTCAE v5.0. RESULTS: At data cutoff (April 9, 2021), 34 pts had been enrolled and 16 pts continued to receive FEDR. Reasons for FEDR Tx D/C in > 1 pt were lack of efficacy (n = 5) AEs (n=4; 1 was Tx-related [G3 thrombocytopenia]), disease progression (n = 2), pt decision (n = 2), and to undergo transplant (n = 2). Median FEDR Tx duration was 28.3 weeks (range 1.6-101.3); 20 pts (59%) had received > 6 Tx cycles and 14 pts (41%) completed > 12 cycles. Median average FEDR dose was 400 mg/d (range 298-400).At BL, median (range) age was 68.5 years (49-82), time from MF diagnosis was 3.4 years (0.1-17.4), and spleen size was 15 cm (3-31). Most pts (62%) had primary MF, and all pts had received ≥ 3 mo of prior RUX Tx; the most common reason for prior RUX D/C was loss of response/Tx failure (41%). During FEDR Tx, 22 pts (65%) received ondansetron and 11 (32%) received loperamide. GI AEs reported in > 10% of pts were constipation (47%), diarrhea (35%), nausea (26%), abdominal pain (24%), and vomiting (18%). The frequency of nausea, vomiting, and diarrhea decreased as Tx continued (Figure). Most GI AEs were G1/2 (including all events of nausea, vomiting and diarrhea) and there were no Tx-related G3/4 GI AEs. No pt required FEDR dose-reduction, interruption, or D/C due to a Tx-related GI AE Overall, Tx-related G3/4 AEs were reported in 11 pts (32%), including anemia in 7 pts (21%), and neutropenia, thrombocytopenia, and hyperkalemia in 2 pts each (6%). The cases of hyperkalemia occurred in the setting of acute renal failure or of relevant concomitant conditions. At BL, 1 pt had a thiamine level below the lower limit of normal (LLN; 70 nmol/L); thiamine level was normalized before the pt received FEDR Tx. Thiamine levels dropped below the LLN during FEDR Tx for 4 pts between cycles 2-3 (and for 1 pt at end of Tx); levels returned to normal for these pts with thiamine supplementation and did not require FEDR interruption or reduction. Five other pts received prophylactic thiamine supplementation. There were no reported cases of WE. CONCLUSIONS: FEDR was generally well tolerated. These data suggest the frequency and severity of GI AEs may be reduced via early implementation of GI prophylaxis. Use of GI-directed therapies may have increased the incidence of low-grade constipation. Monitoring thiamine levels before FEDR initiation and periodically during FEDR therapy is recommended. Figure 1 Figure 1. Disclosures Gupta: Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Constellation Pharma: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Incyte: Honoraria, Research Funding; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Yacoub: Agios: Membership on an entity's Board of Directors or advisory committees; Acceleron Pharma: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Verstovsek: Gilead: Research Funding; Genentech: Research Funding; Ital Pharma: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; CTI BioPharma: Research Funding; PharmaEssentia: Research Funding; Protagonist Therapeutics: Research Funding; Incyte Corporation: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Roche: Research Funding; Sierra Oncology: Consultancy, Research Funding; AstraZeneca: Research Funding; Novartis: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. Mesa: Novartis: Consultancy; CTI: Research Funding; Promedior: Research Funding; AOP: Consultancy; Sierra Oncology: Consultancy, Research Funding; La Jolla Pharma: Consultancy; Genentech: Research Funding; CTI: Research Funding; Celgene: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Pharma: Consultancy; Incyte Corporation: Consultancy, Research Funding; Samus: Research Funding; Gilead: Research Funding; Abbvie: Research Funding. Harrison: BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kiladjian: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Other: Personal fees; Taiho Oncology, Inc.: Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Fazal: Agios: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Jazz Pharma: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Stemline: Consultancy, Honoraria, Speakers Bureau; Taiho: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Tolero: Consultancy. Foltz: Incyte: Research Funding; CTI Biopharma: Research Funding; Constellation: Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sierra: Research Funding; Amgen: Other: Spouse employment and equity ownership.. Miller: CTI: Consultancy, Research Funding; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria; Takeda: Honoraria, Speakers Bureau; Celgene: Speakers Bureau. Gharpure: Bristol Myers Squibb: Current Employment. Hernandez: Bristol Myers Squibb: Current Employment. Wang: Bristol Myers Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; VIR Biotechnology: Current equity holder in publicly-traded company. Talpaz: Imago: Consultancy; Celgene: Consultancy; Constellation: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Other: Grant/research support .

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