Patent Publication Number: US-2016235703-A1

Title: Novel Uses of Neuraminidase Inhibitors in Infectious Diseases

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a divisional of commonly owned U.S. patent application Ser. No. 14/169,076 filed on Jan. 30, 2014, which is a continuation-in-part of commonly owned U.S. patent application Ser. No. 13/612,739 filed on Sep. 12, 2012, which is a continuation-in-part of U.S. patent application Ser. No. 13/024,285 filed on Feb. 9, 2011, which is a continuation of U.S. patent application Ser. No. 11/112,138, now U.S. Pat. No. 7,910,620, filed on Apr. 22, 2005. The entire contents of these prior patent applications are hereby incorporated by reference. 
    
    
     BACKGROUND 
     Many disease causing microorganisms, such as bacteria, fungi, and viruses, play a significant role in producing a myriad of diseases and conditions in humans and animals. Due to their widespread capability of pathogenic infectivity, morbidity and mortality, considerable activity has been devoted towards developing convenient effective methods to help prevent or treat these diseases caused by these pathogens. 
     For example, viruses such as influenza, have a high mortality rate in humans and are devastating to man and animals. It is estimated that more than $1 billion per year is lost in productivity from absence due to sickness from an influenza virus infection. 
     With respect to clinical veterinary medicine, there are many diseases, viral, bacterial, fungal and protozoan, that are detrimental to animals. Viruses, bacteria, protozoan and fungi that cause diseases that effect animals in the food industry, for example, cattle, pigs and chickens can be quite costly and result in billions of dollars lost in the food industry. These same microorganisms can wipe out large masses of domestic animals, such as cats and dogs, since they can be highly contagious and spread quickly, thus being detrimental to veterinary hospitals, kennels, and breeding facilities, resulting in both emotional and monetary loss. Recently, there have been several disease causing microorganisms that have jumped the species barrier, resulting in new variant diseases that are fatal to man. 
     Canine parvovirus (CPV), for example, has a high morbidity and mortality rate and is a life threatening infection that has been estimate to affect up to 1 million dogs per year in the United States. The disease resulting from parvovirus is typically almost always fatal, and there have been very few major advances in the way that dogs with canine parvovirus are treated. As a result, the disease is typically associated with a significant mortality rate. Most of the untreated dogs succumb to the diseases, and even with care, for example, in private practice, mortality rate still is quite high. In addition, the disease from a parvovirus infection is costly, both monetarily and emotionally for the dog&#39;s caretakers. 
     With canine parvovirus, the clinical disease is often characterized by fever, acute gastroenteritis, which can progress rapidly to shock and death. Septicemia and endotoxemia can play an important role in the pathogenesis of canine parvovirus. It has been found that when gnotobiotic (germ free) dogs were infected with canine parvovirus, they did not develop any signs of the illness. Similar findings were made with germ-free cats when exposed with highly pathogenic feline parvovirus. Thus, attempts have been directed to utilize treatments aimed at preventing or treating septicemia and endotoxemia. Unfortunately, these treatments have shown little or no benefit on survival of these animals. 
     Necrotic enteritis (NE), caused by  Clostridium perfringens , is an infectious disease that has been found to have a major impact on poultry production globally, with estimated annual economic loss in the billions. Currently, the use of antibiotics has resulted in antibiotic resistance strains. 
     Similarly, diseases caused by fungal (including yeast) and protozoan infections, can be also be difficult and costly to treat. For example, fungal infections such as those caused by  Candida  species (spp) can be a complicated series of antibiotic, steroid and immunosuppressive therapies, that may show little or no benefit to animals infected by these diseases. Typically, antifungal treatments can take months of various antifungal drugs, each with potential harm to the animal&#39;s organs. 
     Typically,  Candida  infections are reported in areas that contain a layer of mucin between the epithelial cells of the organ and lumen of the organ system. Historically,  Candida  infections can be difficult to treat requiring months of therapy using different antifungal drugs. Antifungal drugs are known to be toxic to the host&#39;s liver and kidney, and so any therapy that shortens the treatment period is significant. Additionally, the use of antibiotics has been known to those skilled in the art to promote and enhance growth of yeast. 
     Conventional methods towards the control of these disease causing microorganisms or pathogens, include vaccination, drug therapy and public health measures. Typically, one method of treatment of these types of diseases is antibiotic therapy, which has been found to be effective against diseases caused by bacteria. Although an invaluable advance, there are disadvantages of using antibiotic therapy, especially when strains of bacteria appear to be resistant to antibiotics. 
     Vaccines have also been used to treat diseases caused by viruses. However, there can be disadvantages involved with the production of suitable vaccines. First, the vaccines derived from whole killed or whole attenuated viruses, may retain residual disease causing activity. Further, vaccines typically are reformulated each year in response to antigenic variation and are known to be ineffective against new viral variants. 
     Additional disadvantages are that medications typically can be expensive, especially if animals are on antibiotics, for example, over a long course of time, eventually often resulting in an agonizing imminent death of these animals. 
     As those skilled in the art would appreciate, there is a need for methods that can decrease the infectivity, morbidity and mortality associated with exposures to such pathogens. Such compositions and methods of treatment should preferably not have the undesirable properties of promoting microbial resistance, or being toxic to the recipient. Still further, there is a need for treatment and prevention in diseases caused by microorganisms that are cost effective and do not take a long period of time. In addition, there is a need to provide treatment of infectious diseases by developing biology based therapies. 
     SUMMARY 
     The present invention is directed towards a method and treatment that meets these needs. 
     This invention provides a method of inhibiting, treating and preventing mucosal diseases, diseases associated with neuraminidase dependent bacteria, fungal, yeast, protozoan and superinfections with a neuraminidase inhibitor. 
     In a preferred embodiment, the present invention uses biology based therapy to treat infectious diseases that have been previously treated with antibiotics, antivirals, or anti-fungals, alone or in combination, with limited success. Where there has been variable success in viruses with antiviral drugs, and antibiotics (conventional therapy), or anti-fungal drugs, neuraminidase inhibitors according to the present invention have been proven to be successful and predictable. In a most preferred embodiment of the present invention, when neuraminidase inhibitors are used in these same diseases, the results have been dramatic. 
     Further, this invention relates to a means for reducing the severity of or preventing a neuraminidase dependent bacterial infection of the mucousal membrane tract following a viral infection by administering an effective amount of a neuraminidase inhibitor alone or in combination with a pharmaceutically acceptable compound prior to or during the course of the neuraminidase dependent bacterial infection, during the course of the superinfection or during the course of the coinfection. 
     Still further, this invention relates to a means for reducing the severity of or preventing a neuraminidase dependent fungal, yeast and protozoan infection by administering an effective amount of a neuraminidase inhibitor alone or in combination with a pharmaceutically acceptable compound prior to or during the course of the neuraminidase dependent infection, during the course of a superinfection or during the course of a coinfection. 
     In one embodiment, the present invention provides methods used for preventing disease or treating animals, including humans, exposed to pathogens or the threat of pathogens. 
     In still a further embodiment of the present invention, there is a method used for preventing animals, including humans, from getting a disease associated with the specific pathogen. For example, the animal is contacted with effective amounts of the compositions prior to exposure to pathogenic organisms. In other embodiments, the animal is contacted with effective amounts of the composition after exposure to pathogenic organisms. Thus, the present invention provides a method of both prevention and treatment of microbial, fungal, yeast and protozoan infections. 
     In preferred embodiments, the present invention provides methods to decrease pathogenic organism infectivity, morbidity and mortality, by using an effective method of treatment where the composition comprises a compound that can include neuraminidase inhibitors. 
     In some preferred embodiment, the compound comprising a neuraminidase inhibitor is oseltamivir (TAMIFLU®, hereinafter referred to as TAMIFLU). 
     In another aspect of the present invention, the composition can include additional compounds, such as antibiotics, and/or antifungal drugs, for example, which can be used in addition to the compound comprising the neuraminidase inhibitor. 
     In specific embodiments of the present invention, the method or treatment is performed for a sufficient amount of time to reduce the virulence factor of the pathogen. 
     In yet another specific embodiment, the pathogen can be selected from the group consisting of bacteria, fungi, yeast and protozoan. 
     In a most preferred embodiment, the current invention provides a method of using neuraminidase inhibitors to treat: 1) infections involving neuraminidase dependent bacteria other than mucosal surfaces (blackleg, necrotic dermatitis), 2) one or more bacteria involving mucosal surfaces (colibacillosis or enteriopathic  E. coli  in all species, respiratory, renal, uterine, and mammary gland infections involving neuraminidase producing bacteria,  Salmonellosis  in all species,  Bordetella  and  Pasteurella  respiratory infection in all species) and 3) superinfections that do involve mucosal surfaces (gastrointestinal, respiratory in all species). 
     In yet another preferred embodiment, the present invention provides a method of using an antiviral drug patented for human influenza to treat neuraminidase dependent bacterial infections, superinfections and coinfections which do not involve the human influenza virus A and/or B, for example, in clinical veterinary medicine. 
     In still another preferred embodiment, the present invention provides unexpected results of almost 100% effectiveness when used at 1 mg/lb every 12 hours for 10 treatments for therapeutic use and every 24 hours for 5 treatments for prophylactic use. 
     Finally, the present invention provides the use of a neuraminidase inhibitor to treat diseases involving neuraminidase dependent bacteria. 
     In a preferred embodiment the use of a neuraminidase inhibitor has been used to inhibit, treat and prevent neuraminidase dependent bacterial infections that are not viral generated dependent infections, from a disease causing microorganism dependent on sialic acid metabolism, comprising administering to an animal in need thereof a therapeutically effective amount of composition comprising one or more compounds, wherein one of the compounds comprises a neuraminidase inhibitor, wherein the neuraminidase inhibitor is any compound that is a structural homologue of sialic acid. 
     More preferably, structural homologue can defined as any compound that is corresponding in structure and origin but not necessary in function of sialic acid. 
     In a preferred embodiment, the neuraminidase dependent bacterial infection, is selected from the group consisting of  Enterococcus faecalis, Clostridium perfringens  and antibiotic resistant bacteria. 
     Preferably, the animal can be cold blooded or warm blooded. Animal includes but is not limited to human beings, canine, feline, bovine, equine, avian, porcine and any other species known to those skilled in the art, for example, sheep goats and rabbits. 
     In a preferred embodiment of the present invention, the use of a neuraminidase inhibitor has been used to treat necrotic enteritis (NE) in poultry. More preferably, the neuraminidase inhibitor comprises  Tamerindus Indicus  and  Combretum fragrans.    
     In yet another preferred embodiment of the present invention, the use of a neuraminidase inhibitor has been used to treat feline  Enterobacteria faecalis  sinusitis. More preferably, the neuraminidase inhibitor is oseltamivir (TAMIFLU®). 
     In the most preferred embodiment of the present invention, oseltamivir (TAMIFLU®) has been used to treat canine and feline parvoviral enteritis, canine kennel cough, feline upper respiratory infections, feline nephritis secondary to  E. coli , parvoviral enteritis in raccoons and feline  Enterobacteria faecalis  sinusitis. Given the unique and universal role that sialic acid is known to play in infectious diseases involving neuraminidase dependent bacteria, the concept in the use of a neuraminidase inhibitor would be successful in treating all diseases involving these bacteria regardless of animal species is expected. Animal includes but is not limited to human beings, canine, feline, bovine, equine, avian, porcine and any other species known to those skilled in the art, for example, sheep goats and rabbits. 
     In yet another most preferred embodiment, the current invention provides a method of using neuraminidase inhibitors to treat, prevent and inhibit infections involving neuraminidase dependent pathogens, wherein the pathogen is capable of producing neuraminidase as a virulence factor, 
     Several fungal species are known to have neuraminidase activity including  Candida fumata.    
     Several protozoan species are known to have neuraminidase activity including but not limited to tritrichomonase foetus. 
     In yet another preferred embodiment, the present invention provides a method of using an antiviral drug patented for human influenza to treat neuraminidase dependent bacterial infections, superinfections and coinfections which do not involve the human influenza virus A and/or B, for example, in clinical veterinary medicine. 
     In still another preferred embodiment, the present invention provides unexpected results of almost 100% effectiveness when used at 1 mg/lb every 12 hours for 10 treatments for therapeutic use and every 24 hours for 5 treatments for prophylactic use. 
     Finally, the present invention provides the use of a neuraminidase inhibitor to treat diseases involving neuraminidase dependent bacteria. 
     In the most preferred embodiment of the present invention, oseltamivir (TAMIFLU®) has been used to treat canine and feline parvoviral enteritis, canine kennel cough, feline upper respiratory infections, feline nephritis secondary to  E. coli , and parvoviral enteritis in raccoons. Given the unique and universal role that sialic acid is known to play in infectious diseases involving neuraminidase dependent bacteria, the concept in the use of a neuraminidase inhibitor would be successful in treating all diseases involving these bacteria regardless of animal species is expected. Animal includes but is not limited to human beings, canine, feline, bovine, equine, avian, porcine and any other species known to those skilled in the art, for example, sheep goats and rabbits. 
     In yet another preferred embodiment of the invention, there is provided a method for inhibiting, treating and preventing, neuraminidase dependent infections from a disease-causing microorganism dependent on sialic acid metabolism, wherein the microorganism comprises a pathogen capable of producing neuraminidase as a virulence factor, the method comprising administering to an animal in need thereof a therapeutically effective amount of a composition comprising one or more compounds, wherein one of the compounds comprises neuraminidase inhibitors. 
     The neuraminidase dependent infection can be selected from the group consisting of bacterial, fungal, yeast and protozoa. 
     The neuraminidase inhibitor is selected from the group consisting of zamanivir (Relenza), oseltamivir (Tamiflu), rimantadine, rimantadine hydrochloride, amantadine, ribavirin, and leaves and stem bark from  Tamarindus indicus  ( T. indicus ) and  Combreton fragrans  ( C. fragrans ), and the like, and any structural homologue of sialic acid, and any drug that are synthetic sialic acid analogs that can inhibit action of viral, bacterial, fungal, protozoan and eukaryotic neuraminidases. 
     Preferably, the neuraminidase inhibitor is any structural homologue of sialic acid. 
     Preferably, the neuraminidase inhibitor is oseltamivir. 
    
    
     DESCRIPTION 
     According to the present invention, there is provided novel uses of selective neuraminidase inhibitors effective in shortening or stopping the pathophysiology of diseases involving one or more pathogens that require neuraminidase as a virulence factor. 
     Neuraminidase 
     Neuraminidases, (also known as sialidases) are known to those skilled in the art as enzymes that have been identified in many viruses, bacteria, fungi, including yeast, and eukaryotes that cleave sialic acid moieties and can be involved in many functions in vivo. It has been shown that neuraminidases can play a significant role in the pathogenesis of infectious diseases, whose etiologic agents produce neuraminidase to cleave sialic acids in infected tissues to facilitate their ability to invade a host. It has been shown that there is a positive correlation between the level of production of sialidases and the virulence of various bacterial, fungal, including yeast, and protozoan strains. This virulence is further enhanced by different bacteria being able to produce more than one sialidase. Thus, many disease causing microorganisms possess a neuraminidase. 
     One example of a neuraminidase inhibitor that has been approved for the treatment of human influenza, is oseltamivir (TAMIFLU®, F. Hoffman-La Roche, Switzerland) and zanamivir (RELENZA®, Glaxo Wellcome, Inc., hereinafter referred to an RELENZA). Oseltamivir is a synthetic sialic acid analog that has been modified at the C4 position. Synthetic sialic acid analogs, such as oseltamivir have been demonstrated to inhibit the action of neuraminidases. Since their introduction in 1999, zanamivir and oseltmivir have been used successfully to treat human influenza A and B viral infections. In humans, neither zanamivir nor oseltamivir has been demonstrated to be effective in preventing serious influenza-related complications, such as bacterial or viral pneumonia or exacerbation of chronic diseases. Development of viral resistance to zanamivir and oseltamivir during treatment has been identified but does not appear to be frequent. 
     In some pathogens, including many enteric bacteria, neuraminidases typically are recognized as virulence factors. Neuraminidases cleave terminal sialic acid residues from cell surface molecules such as glycoproteins and glycolipids. As a result of this cleavage, internal sugar residues can be exposed that are normally protected and not available to pathogens. Neuraminidase activity can be particularly important for bacterial adhesion to mucosal surfaces. Mucous typically is highly sialylated and can be a major component of innate mucosal immunity. In mucosal diseases, commensal bacteria are separated from epithelial cells by a mucous barrier. Pathogenic bacteria have been shown to produce sialidases which can decrease the viscosity of the mucous and thus enable the bacteria to colonize on the epithelial cell membrane. Once in contact with the epithelial cell, a pathogen can become attached. With bacterial colonization and proliferation, there can be detachment and depletion of immunoglobin IgA. Bacterial endotoxins and exotoxins can be released resulting in local and distant tissue damage. Bacterial neuraminidases (sialidases) can cause the dissolution of the neuraminic acid located within the intercellular cement of the epithelial cells, allowing bacteria, their endotoxins, exotoxins and any environmental free sialic acid to enter the submucosa. 
     According to the present invention, it is known to those skilled in the art, the mechanism of hydrolyses of sialic acid compound during neuraminidase inhibition and pathogens that use sialic acid, is fully described and incorporated herein by reference in its entirety (Vrim et al., Microbiology and Molecular Biology Reviews, March 2004, p. 132-153). 
     A definitive role of neuraminidase activity in, for example, canine parvoviral infections, has not been established and it is thought that canine parvovirus does not have a neuraminidase in its genome. However, in one preferred embodiment of the present invention, it has been found that it is not essential for canine parvovirus to contain or utilize neuraminidases in order for them to enhance pathogenicity. Neuraminidases have been known to demonstrate enhanced pathogenicity in a synergistic fashion in several viral and bacterial superinfections involving mucosal surfaces. In some cases, for example, pneumococcal pneumonia secondary to influenza, viral neuraminidase activity enhanced the adhesion of the bacteria to the mucosal surface that resulted in increased bacterial invasion into tissues and resistant bacterial superinfection. Neuraminidases of bacterial origin alone are known as vitally important virulence factors. 
     According to the present invention, as used herein, the Theory of Biological Intervention states that one can treat infectious diseases by suppressing or inhibiting one of more of the pathogen&#39;s virulence factors, wherein the virulence factor can be neuraminidase. 
     In a preferred embodiment of the present invention, a neuraminidase inhibitor is given and results in remission of clinical signs, the pathogen(s) can be identified as being neuraminidase producers or dependent. This is because of the singular specificity of a neuraminidase inhibitor stopping the removal of sialic acids from the host cell&#39;s glycoprotein, glycolipids and polysaccharides. 
     The enzyme neuraminidase (sialidase) is a virulence factor produced and secreted by the infectious organism (regardless of genus or species) to remove neuramic (sialic acid) molecules from the host&#39;s (regardless of genus or species) cells and tissues. 
     According to the present invention, regardless of the genus or species of the organism and host, there is only one enzymatic reaction associated with the removal of sialic acid from the host&#39;s cells and tissues. 
     Preferably, neuraminidase inhibitors are homologues of each other regardless of their source. Every neuraminidase inhibitor is also a homolog of neuramic (sialic) acid and inactivates the pathogen&#39;s neuraminidase by combining with its terminal end designed to attach and remove the host&#39;s neuramic (sialic) acid. The inactivated neuraminidase is prevented from removal of neuramic (sialic)acid from the host, and thus prevents or limits the degree of infection. 
     Sialic acid is known to those skilled in the art as a 9—carbon compound. 
     
       
         
         
             
             
         
       
     
     In a preferred embodiment of the present invention, neuraminidase (sialidase) is the enzyme produced by neuraminidase producing organisms to remove neuraminic (sialic) acid molecules from the host&#39;s cells and tissues. The site of neuraminidase attachment is structurally homologous to that of the targeted neuraminic (sialic) acid attached to the host&#39;s cells or tissues. 
     Preferably regardless of the genus and species of the host or pathogen, the enzymatic reaction where the pathogen&#39;s neuraminidase attaches and removes the host&#39;s sialic acid molecule is a singular identical reaction. 
     
       
         
         
             
             
         
       
     
     More preferably, Neuraminidase inhibitors combine with the active site of the pathogen&#39;s neuraminidase enzyme and in doing so, prevent the secreted neuraminidase from attaching to and removing the sialic acid molecules from the terminal ends of the host&#39;s glycoproteins, glycolipids and polysaccharides. 
     More preferably, regardless of the original source for a neuraminidase inhibitor, every neuraminidase inhibitor is a homolog to any other neuraminidase inhibitors and also to sialic acid. This homologous feature of neuraminidase inhibitors explains how to inhibit neuraminidases from different bacteria ( Clostridium  and  Enterobacteria ) by using neuraminidase inhibitors from 3 different plants ( Illicium anisatum, Tamarindus indicus  and  Combretum fragrans ). 
     
       
         
         
             
             
         
       
     
     Preferably, the chemical and medical complexities associated with the current approach to infectious diseases are reduced to the inhibition of one simple enzymatic reaction by any one of a group of homologs of sialic acid called neuraminidase inhibitors. 
     The present invention provides the use of neuraminidase inhibitor to treat diseases involving neuraminidase dependent bacteria. Evidence to support this theory includes the following. It is known that the Fulani Pastoralists of rural Nigeria prevented blackleg infections in their cattle by feeding them the stem bark from two plants ( Tamarindus indicus  and  Combretum fragrans ). These plants contained neuraminidase inhibitors in their stem bark. Blackleg is a lethal disease in cows caused by a neuraminidase dependent bacteria  Clostridium chauvoei . In one preferred embodiment of the present invention, it has been demonstrated that bacteria must be present in the disease causing microorganism, for example, parvovirus infection, to result in significant pathology. Typically, germ free animals do not demonstrate any of the clinical disease that is seen in normal animals when they are challenged with virulent parvovirus strains. The pathology is thought to be attributed to septicemia and endotoxemia and is believed to originate from enteric bacteria. Several enteric bacterial species are known to have neuraminidase activity including  Escherichia coli, Campylobacterium, Salmonella, Shigella, Staphylococcus  and  Clostridium . From the list, at least two of these species,  E. coli  and  Clostridium , have been associated with morbidity and mortality in dogs with parvovirus. 
     In addition, germ-free kittens and germ-free puppies when exposed to pathogenic strains of feline and canine parvovirus, did not develop any clinical signs. It is known to those skilled in the art that the commensal microflora of puppies contains neuraminidase dependent bacteria (Strep.,  E. coli , Staph.,  Clostridium, peptostreptococci, lactobacilli ). According to the present invention, it has been shown that  E. coli  and  Clostridium  have been associated with morbidity and mortality in dogs with parvovirus. In addition, neuraminidases have been demonstrated to enhance pathogenicity in a synergistic fashion in some viral and bacterial superinfections involving mucosal surfaces. Still further, the role of sialic acid metabolism in commensal and pathogenic strains of neuraminidase dependent bacteria provides support for the methods used in accordance with the present invention. Further evidence supporting the role of neuraminidases in infectious diseases includes knowing that the histopathological lesions associated with canine parvoviral enteritis were typical of those created by bacterial septicemia and endotoxemia. 
     In addition, most if not all of these commensal bacteria produce neuraminidase in order to provide sialic acid to use in their metabolic pathways. When canine parvovirus exits an infected gastrointestinal(GI) epithelial cell, sialic acid is released into the GI tract. The commensal bacteria begins to colonize and proliferate and produce their own neuraminidase. This excess neuraminidase can provide additional sialic acid and can also dissolve the neuraminic acid in intercellular cement providing a portal to submucosal tissue. In addition, neuraminidase can also displace epithelial cells&#39; IgA. 
     Interleukin-8 is known as a cytokine produced by many cell types including endothelial cells, fibroblast, respiratory epithelial cells, macrophages and PMNs. With the release of IL-8, the PMNs can mobilize intracellular sialidases that move to their cell membrane and causes the release of sialic acid from the membrane surface. The removal of sialic acid residues from the PMN&#39;s cell membrane allows them to attach to the endotheial cell wall and move by diapedesis towards the tissues containing high levels of IL-8. 
     High levels of neuraminidase can also stimulate dendritic cells to interact with macraphages. Both CD4 and CD8 lymphocytes can also be stimulated to produce Th1 and Th2 cytokines. 
     Thus, in a preferred embodiment of the present invention, canine and feline parvoviral enteritis is shown to be a superinfection (requiring a virus+neuraminidase dependent bacteria living on a mucous substrate). The pathology seen at necropsy is solely due to endo and exotoxins produced by the commensal bacteria turned pathogenic. In a preferred embodiment of the present invention, parvoenteritis is not known as a viral disease, but that the pathobiology is due to excess neuraminidase. Thus, when a neuraminidase inhibitor like TAMIFLU is administered early in the course of the disease or as a prophylactic, one can prevent the production of neuraminidase (sialidase) and one can prevent the commensal bacteria from becoming pathogenic. 
     As used herein, “neuraminidase dependent bacteria” includes “neuraminidase producing bacteria.” 
     In still yet another preferred embodiment of the present invention, the neuraminidase inhibitors can be used to target neuraminidase dependent bacterial infections, superinfections, and coinfections and not dependent on viral neuraminidase. 
     In still yet another preferred embodiment of the present invention, the neuraminidase inhibitors can be used to target neuraminidase dependent fungal, yeast and protozoan infections. 
     In one preferred embodiment of the present infection, “superinfection”, as used herein, means that an infection requires both virus and bacteria combined together to produce pathology more severe than either can alone. 
     “Coinfection”, as used herein, means two or more different bacterial strains together to produce pathology of a disease more severe than either can alone. 
     As used herein, the term “pathogen” refers to a microbe producing one or more virulence factors of which neuraminidase is one of. According to the present invention, the difference between pathogen and commensal bacteria is that commensal bacteria are not producing neuraminidase as virulence factors. 
     By the term “animal”, as used herein, can be any animal species, warm blooded or cold blooded, including a human being, who is infected with, or is likely to be infected with, microorganism producing disease, which are believed to be pathogenic. Animal includes but is not limited to human beings, canine, feline, bovine, equine, avian, porcine and any other species known to those skilled in the art, for example, sheep goats and rabbits. 
     The inhibitors of interest in this invention are neuraminidase dependent bacteria inhibitors. Of particular interest are those which are specific for the neuraminidase enzyme. Since many commensal and pathogenic bacteria also used environmental (hosts) sialic acids as sources of carbon, nitrogen, energy and amino sugars for cell wall synthesis, microbial sialic acid metabolism has been established as a virulence determinant in a range of infectious diseases. Both commensal and pathogen bacteria have been known to modify their cell membranes with sialic acids in order to masquerade as “self” to avoid, obvert or inhibit host&#39;s innate immunity. Dehydration at the sialic acid reducing ends, leading to formation of a planar structure known as N-acetyl-2,3-didehydro-2-deoxyneuraminic acid (diddeoxyNeu5Ac [Neu5Ac2en]. The flattened Neu5Ac2en ring mimics the transition state during hydrolysis of sialoglycoconjugates (Sia-O-acceptors) by glycosylhydrolases designated sialidases (synonymous with neuraminidase). Neu5Ac2en is typically known as a sialidase or neuraminidase inhibitor. In particular, a preferred group of inhibitors are those neuraminidase inhibitors which are similar in structure to Neu5Ac2en. For example, Neu5Ac2en has been known to those skilled in the art, to serve as the lead compound for synthesis of one of the most well known sialidase inhibitor, zanamivir (RELENZA). Most preferably, the neuraminidase inhibitors according to the present invention are those compounds that hydrolyze sialic acid. 
     In yet a more preferred embodiment of the present invention, the neuraminidase inhibitor is any compound that is a structural homologue of sialic acid. 
     “Structural homologue” as used herein, is defined as any compound that is corresponding in structure and origin but not necessary in function of sialic acid. As used herein, neuraminidase inhibitors are structural homologues to each other and of sialic acid. 
     “Neuraminidase dependent infections” as used herein, are based on the metabolism of sialic acid, which is dependent on one enzymatic reaction, and can be controlled using a neuraminidase inhibitor from any source, since neuraminidase inhibitors are homologues of each other and sialic acid. The enzymatic reaction in which neuraminidase initiates and controls the rate of a chemical reaction that involves the cleavage of glucosidic linkage between a sialic acid residue and a hexose or hexoamine residue at the non-reducing terminal of oligosaccharides in glycoproteins, glycoplipids and proteoglycans, and is a single specific enzymatic reaction that is not influenced by the animal species or sex. A “neuraminidase inhibitor”, as used herein, is any compound that is a homologue of sialic acid, and can inhibit this specific enzymatic reaction. 
     Specifically, with respect to “Theory of Biological Intervention” where one can treat infectious diseases by suppressing or inhibiting one ore more of the pathogen&#39;s virulence factors, it is known to those skilled in the art that protozoan ( Tritrichomonas  spp) and yeast ( Candida  spp), are neuraminidase producers and produce neuraminidase as a virulence factor. 
     In yet another preferred embodiment, the present invention also provides the use of neuraminidase inhibitor to treat, inhibit and prevent diseases involving neuraminidase as a virulence factor including but not limited to fungi, including yeast, protozoan and bacterial infections in which the pathogen is neuraminidase producer. Evidence to support this theory includes the following. Several fungal and protozoan species are known to have neuraminidase activity including  Candida fumata  for yeast; and  Tritrichomonas foetus  for protozoan. 
       Candida  infections typically are reported in areas that contain a layer of mucin between the epithelial cells of the organ and lumen of the organ system. Historically, they can be very difficult to treat requiring months of therapy using different antifungal drugs. 
     Antifungal drugs are known to those skilled in the art to be toxic to the host&#39;s liver and kidney, and so any therapy that shortens the treatment period is significant. 
     The introduction of oseltamivir phosphate to suppress the pathogen&#39;s ( Candida famata ) production of neuraminidase greatly shortened the clinical disease from weeks to 72 hours. This case is an example of using the Theory of Biological Intervention in a clinical yeast/fungal infection. The Theory of Biological Intervention states that one can treat most infections by suppressing one of more of the pathogen&#39;s virulence factors. In this case, neuraminidase is a virulence factor of  Candida famata  ( C. famata ). 
     It is known to those skilled in the art that  Candida  is a genus of yeast. The use of the term  Candida  often refers to a complex with broad spectrum of symptoms, the majority which center around, for example, gastrointestinal distress, rashes, and sore gums. Other  Candida  species include but are not limited to  C. famata; Candida albicans  ( C. albicans , also known to those skilled in the art as thrush);  C. glabrata  and  C. rugosa.    
     Preferably, since bacteria, protozoan and fungi (yeast) produce neuraminidase as virulence factors, according to the “Theory of Biological Intervention”, protozoan, fungi, yeast, bacterial and viral infections can be treated, inhibited and prevented using a therapeutically effective amount of a composition comprising one or more compounds. Preferably, one of the compounds comprises neuraminidase inhibitors. 
     With respect to  Candida  spp, neuraminidase can degrade protective mucin layer in a gastro intestinal (GI) tract and allows  Candida  spp to attach to the tissues. Neuraminidase inhibitors of the present invention, can block the production of neuraminidase by  Candida  spp and suppress the  Candida  infection. Moreover, neuraminidase inhibitors (not limited to oseltamivir phosphate, for example) can be used in combination with an antifungal drug (such as Itraconazole, for example). Typical antifungal treatments typically can take months of various antifungal drugs, each with potential harm to the animal&#39;s liver and kidneys. 
     According to an embodiment of the invention, protozoan infections (such as  Tritrichomonas  spp) can be treated with neuraminidase inhibitors.  Tritrichomonas  spp preferably can include  Tritrichomonas foetus  ( T. foetus ).  T. foetus  typically is known to those skilled in the art as an obligate parasite of the bovine urogenital tract producing infection associated with inflammatory changes, abortion and infertility. Typically, although the two  tritrichomonas  have different habitats, both protozoans are known to use lectins with sialic acid specificity for adhesion to mucosal surfaces. Typically, the drug, Ronidazole is effective to treat  T. foetus  in cats. However, Ronidazole, a nitroimidazole, has many side effects and is known to be carcinogenic. Cats that have been given Ronidazole have been known to develop ataxia, nystagmus and behaviour changes. These signs of neurotoxicity have shown to be reversible when Ronidazole was discontinued. 
     One of the virulence factors produced by  T. foetus  is neuraminidase. Neuraminidase is an enzyme that when exposed to glycoproteins found in body tissues can release a nine carbon compound called neuramic or sialic acid. This compound typically is found in every living thing and therefore is known as a basic building block in nature.  T. foetus  secrets neuraminidase into the gastrointestinal (GI) lumen and it can dissolve the mucin layer between the GI contents and the GI epithelial cells. Neuraminidase also is known to denature IgA attached to the GI epithelial cell and also alters the GI epithelial cell membrane to allow  T. foetus  to colonize and reproduce by using the freed neuramic acid molecules. 
     Oseltamivir phosphate is a neuraminidase inhibitor that has been shown to inhibit neuraminidases produced by GI organisms in parvoenteritis. Given the choice of using ronidazole or bloody diarrhea for up to two years, it was decided to use oseltamivir phosphate to see what suppressing  T. foetus &#39; ability to secrete neuraminidase would do to the clinical course of this infection. 
     In a preferred embodiment the use of a neuraminidase inhibitor has been used to inhibit, treat and prevent neuraminidase dependent bacterial infections that are not viral generated dependent infections, from a disease causing microorganism dependent on sialic acid metabolism, comprising administering to an animal in need thereof a therapeutically effective amount of composition comprising one or more compounds, wherein one of the compounds comprises a neuraminidase inhibitor, wherein the neuraminidase inhibitor is any compound that is a structural homologue of sialic acid. 
     More preferably, structural homologue can defined as any compound that is corresponding in structure and origin but not necessary in function of sialic acid. 
     Also included are resistant bacteria where the pathogen can be a gram (+) rod bacteria and where potential drugs alone were ineffective (for example, the bacteria were resistant). Also included in an embodiment of the present invention are bacterial infections in the frontal sinus regions which can be difficult to treat. 
     In a preferred embodiment, the present invention provides the use of neuraminidase inhibitor to treat a neuraminidase dependent bacterial infection, selected from the group consisting of  Enterococcus faecalis , ( E. faecalis , which affects the sinuses),  E. coli  in the kidney  Clostridium perfringens  (Necrotic enteritis) and antibiotic resistant bacteria. 
     Preferably, the animal can include cold blooded animals and warm blooded animals. Animal includes but is not limited to human beings, canine, feline, bovine, equine, avian, porcine and any other species known to those skilled in the art, for example, sheep goats and rabbits. 
     In a preferred embodiment of the present invention, the use of a neuraminidase inhibitor has been used to treat necrotic enteritis (NE) in poultry. More preferably, the neuraminidase inhibitor comprises  Tamerindus Indicus  and  Combretum fragrans.    
     In yet another preferred embodiment of the present invention, the use of a neuraminidase inhibitor has been used to treat feline  Enterobacteria faecalis  sinusitis. More preferably, the neuraminidase inhibitor is oseltamivir (TAMIFLU®). 
     According to a preferred embodiment of the present invention, Theory of Biological Intervention states that one can treat many infections by suppressing one or more of the pathogen&#39;s virulence factors. By suppressing one or more of the pathogen&#39;s virulence factors does not kill the organism, but does prevent the invasion of the host&#39;s body tissues while also denying or reducing the supply of carbon compounds normally used by the organism for energy and building blocks to reproduce and colonize on the host&#39;s tissues. 
     Treatment 
     According to one embodiment of the present invention, an effective amount of compound, preferably a neuraminidase inhibitor can be administered to an animal. Typically, when a parvovirus infected animal presents symptoms such as vomiting/nausea and pain, traditional treatment involves administering fluids and cortisone for shock, antibiotics therapy and medicine for pain. In addition, anti-emetics can be administered to help alleviate nausea and vomiting. 
     The neuraminidase inhibitor can be administered in several ways: i) at the start of or during the course of the neuraminidase dependent bacterial infection, or some part thereof; or ii) at the start of or during the course of a superinfection infection or some part thereof; or iii) at the start of or during the course of a coinfection or some part thereof. In addition, the inhibitor can be administered prior to the onset of a neuraminidase dependent bacterial infection, superinfection or coinfection, and preferably continued for some period during the course of the bacterial infection, superinfection or coinfection. In a most preferred embodiment of the present invention, the neuraminidase inhibitor can be administered during the entire, or part of the length of a bacterial infection, a superinfection or a co-infection. 
     The neuraminidase inhibitor can also be administered in several ways: i) at the start of or during the course of the neuraminidase dependent bacterial, fungal, yeast and protozoan infection, or some part thereof; or ii) at the start of or during the course of a superinfection infection or some part thereof; or iii) at the start of or during the course of a coinfection or some part thereof. In addition, the inhibitor can be administered prior to the onset of a neuraminidase dependent bacterial, fungal, yeast and protozoan infection, superinfection or coinfection, and preferably continued for some period during the course of the bacterial, fungal, yeast and protozoan infection, superinfection or coinfection. In a most preferred embodiment of the present invention, the neuraminidase inhibitor can be administered during the entire, or part of the length of a bacterial, fungal, yeast and protozoan infection, a superinfection or a co-infection. 
     Most preferably, the neuraminidase inhibitor is administered within 48 hours of onset of first clinical signs. 
     By the term “an effective amount” is meant an amount of the compound in question which will in a majority of animals have either the effect that the disease caused by the pathogen is cured or, if the substance has been given prophylactically, the effect that the disease is prevented from manifesting itself. The term “an effective amount” also implies that the substance is given in an amount which only causes mild or no adverse effects in the animal to whom it has been administered, or that the adverse effects may be tolerated from a medical and pharmaceutical point of view in the light of the severity of the disease for which the substance has been given. 
     For the purposes of this invention, it is preferred to administer an effective amount of the neuraminidase inhibitor in an amount from about 0.6 mg/lb to 12 mg/lb, more preferably 0.3 mg/lb to 10 mg/lb, and most preferably 1 mg/lb of the active ingredient. Too high a dose of neuraminidase inhibitor can be toxic. Too low of a dose may not be effective enough to treat or prevent the neuraminidase dependent disease. 
     The neuraminidase inhibitor can be administered by any route. The route of administration of the substance could be any conventional route of administration, i.e. oral, intravenous, intramuscular, intradermal, subcutaneous etc. A preferred formulation will be the oral route; oral immediate release tablet or an oral controlled release tablet. For treatment of a disease caused by a microorganism, the neuraminidase inhibitor can be administered up to 6 times per day, though twice or once a day dosing regime is preferred. More preferably, 10 doses over a period of 5 days. Most preferably, 6 doses over a period of 3 days or until the animal&#39;s health improves. 
     In yet another preferred embodiment of the present invention, for prevention of a disease caused by a microorganism, the neuraminidase inhibitor can be administered once a day for 5 days. Typically, with animals infected with parvovirus, administering the neuraminidase inhibitor with the first dose will stop the vomiting. After the 2 nd  dose, the diarrhea will cease. By the 6 th  dose, most clinical signs of the infection will have ceased. 
     In one preferred embodiment, a composition can be administered to an animal, the composition comprising a compound. The compound preferably is a selective neuraminidase inhibitor. The neuraminidase inhibitor can be used alone or in combination with any other neuraminidase inhibitor. More preferably, the compound is a neuraminidase inhibitor which is selective towards neuraminidase dependent bacteria. Preferably, the neuraminidase inhibitor can be selected from the group consisting of zanamivir (RELENZA®, Glaxo Wellcome, Inc.), oseltamivir (TAMIFLU®, F. Hoffmann La Roche, Switzerland), rimantadine, rimantadine hydrochloride, amantadine, ribavirin, and leaves and stem bark from  Tamarindus indicus  ( T. indicus ) and  Combreton fragrans  ( C. fragrans ), and the like and any drug that are synthetic sialic acid analogs that can inhibit action of viral, bacterial, fungal, yeast, protozoan and eukaryotic neuraminidases. Preferably, the neuraminidase inhibitor is any compound that is a structural homologue of sialic acid. More preferably, the structural homologue is any compound that is corresponding in structure and origin, but not necessary in function, of sialic acid. Most preferably, the compound is a neuraminidase inhibitor that is oseltamivir. Oseltamivir (TAMIFLU®) is available from Roche Pharma™ AG (Switzerland). Alternatively, oseltamivir can be prepared according to the methods described in U.S. Pat. No. 5,763,483 to Bischofberger et al and U.S. Pat. No. 5,866,601 to Lew et al., the disclosures of which are hereby incorporated by reference. Preferably, the neuraminidase inhibitor comprises  Tamerindus indicus  and  Combretum fragrans.    
     While the administration of neuraminidase inhibitor as the sole compound of the composition is most preferred, one or more of these neuraminidase inhibitors can be combined with other compounds for treating bacterial infections, fungal infections, yeast infections, protozoan infections, superinfections and coinfections. For example, a neuraminidase inhibitor could be co-administered with a treatment during the course of the neuraminidase dependent infection. Examples of drugs that can also be used in combination with one or more other compounds without limitation, are anti-infective agents and/or other agents used to treat other acute or chronic ailments which include, antimicrobial compounds (such as antibiotics), antifungal compounds, antiviral compounds, anticancer compounds, vitamins, trace metal supplements, or ionic buffers designed to maintain or correct proper ionic balance in blood or other tissues, such drugs are alpha and beta interferon, Inosine pranobex, moroxydine hydrochloride and the like. If antibiotics are used, preferably, the antibiotic is selected from the group consisting of penicillins, benzylpenicillin, amoxycillin, ampicillin, cephalosporins, erythromycin and co-trimoxazole. 
     Typically, Itraconazole can be used as an antifungal. 
     Appropriate dose ratio between a compound of the present invention and a second therapeutic compound for co-administration to an animal will be readily appreciated by those skilled in the art. Clearly, the combination therapies described herein are merely exemplary and are not meant to limit possibilities for other combination treatments or co-administration regimens. 
     EXAMPLES 
     The following examples show the importance of neuraminidase dependent bacteria in mucosal infections in several animal species. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Veterinary Diseases 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Dog 
                 Cat 
                 Cow 
                 Pig 
                 Horse 
                 Avian 
                 Other 
               
               
                   
               
               
                 
                   Actinobacillus 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
                   
               
               
                 
                   Actinomyces 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Aeromonas 
                 
                 + 
                   
                 + 
                 + 
                   
                 + 
                 + 
               
               
                 
                   Bacteroides 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
                 + 
               
               
                 
                   Bordetella 
                 
                 + 
                 + 
                   
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Brucella 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
                 + 
               
               
                 
                   Campylobacter 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Clostridium 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Corynebacterium 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Enterobacter 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
                   
               
               
                 
                   E. coli 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Erysipelothrix 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Fusobacterium 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
               
               
                 
                   Klebsiella 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
                   
               
               
                 
                   Pasturella 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Mannheimia 
                 
                   
                   
                 + 
                   
                   
                   
                 + 
               
               
                 
                   Peptostreptococcus 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
               
               
                 
                   Proteus 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Pseudomonas 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Rhodococcus 
                 
                   
                 + 
                   
                   
                 + 
                   
                   
               
               
                 
                   Salmonella 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Serratia 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Shigella 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                   
                 + 
               
               
                 
                   Staphlococcus 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Streptococcus 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Vibrio 
                 
                   
                   
                   
                   
                   
                 + 
                 + 
               
               
                 
                   Haemophilus 
                 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
                 + 
               
               
                 
                   Arcanobacterium 
                 
                 + 
                 + 
                 + 
                 + 
                   
                   
                 + 
               
               
                   
               
            
           
         
       
     
     Neuraminidase dependent bacteria are those known to use sialiac acid (neuraminic acid) either as a source for carbon, nitrogen, energy and amino acids for cell wall synthesis. This microbial sialic acid metabolism is known to be a virulence factor in a number of infectious diseases. Tables (9-14) representing specific diseases in the various species are included. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Superinfections in Veterinary Medicine 
               
            
           
           
               
               
               
               
               
            
               
                 Species: 
                 Disease 
                 Virus 
                 Bacteria 
                 Other 
               
               
                   
               
               
                 Canine 
                 Parvoviral Enteritis 
                 Canine Parvovirus 
                 
                   Clostridium 
                 
                 
                   Salmonella 
                 
               
               
                   
                   
                 CPV-2b &gt; CPV-2a 
                 
                   E. coli 
                 
                 
                   Peptostreptococcus 
                 
               
               
                   
                   
                   
                 
                   Streptococcus 
                 
                   
               
               
                   
                   
                   
                 
                   Staphylococcus 
                 
                   
               
               
                   
                 Tracheobronchitis 
                 Canine Adenovirus-1 
                 
                   Bordetella bronchiseptica 
                 
                 
                   Streptococcus 
                 
               
               
                   
                 (Kennel Cough) 
                 Canine Adenovirus-2 
                   
                 
                   Pasturella 
                 
               
               
                   
                   
                 Canine Parainfluenza 
                   
                 
                   Pseudomonas 
                 
               
               
                   
                   
                   
                   
                 
                   Klebsiella 
                 
               
               
                   
                   
                   
                   
                 
                   E. coli 
                 
               
               
                 Feline 
                 Parvoviral Enteritis 
                 Feline Parvovirus 
                 
                   Clostridium 
                 
                   
               
               
                   
                 (Panleukopenia) 
                   
                 
                   E. coli 
                 
                   
               
               
                   
                   
                   
                 
                   Streptococcus 
                 
                   
               
               
                   
                   
                   
                 
                   Staphylococcus 
                 
                   
               
               
                   
                   
                   
                 
                   Peptostreptococcus 
                 
                   
               
               
                 URI 
                 Feline Rhinotracheitis 
                 Feline Herpesvirus-1 
                 
                   Bordetella bronchiseptica 
                 
                 
                   Streptococcus 
                 
               
               
                 Complex 
                   
                   
                   
                 
                   Pasturella 
                 
               
               
                   
                   
                   
                   
                 
                   Pseudomonas 
                 
               
               
                   
                 Feline Calicivirus 
                 Feline Calicivirus 
                 
                   Bordetella bronchiseptica 
                 
                 
                   Klebsiella 
                 
               
               
                   
                   
                   
                   
                 
                   E. coli 
                 
               
               
                   
                   
                   
                   
                 
                   Chlamydia 
                 
               
               
                 Bovine 
                 Enzootic Pneumonia 
                 Parainfluenza-3 (Pi-3) 
                 
                   Pasturella multocida 
                 
                 
                   Mycoplasma dispar 
                 
               
               
                   
                   
                 Bovine Respiratory 
                 
                   Arcanobacterium 
                 
                 
                   Mycoplasma bovis 
                 
               
               
                   
                   
                 Syncytial Virus (BRSV) 
                 
                   pyognes 
                 
                 
                   Ureaplasma 
                 
               
               
                   
                   
                 Bovine Herpes -1 
                 
                   Haemophilus somnus 
                 
                 
                   Chlamydia 
                 
               
               
                   
                   
                 Reoviruses 
                 
                   E. coli 
                 
                   
               
               
                   
                   
                 Rhinoviruses 
                   
                   
               
               
                   
                 Shipping Fever or 
                 Pi-3 
                 
                   Mannheimia haemolytica 
                 
                 
                   Pasteurella multocida 
                 
               
               
                   
                 Pneumonic pasteurellosis 
                 BRSV 
                   
                   
               
               
                   
                   
                 BHV-1 
                   
                   
               
               
                   
                 Infectious Bovine 
                 Bovine Herpes-1 
                 
                   Mannheimia haemolytica 
                 
                 
                   Pasteurella multocida 
                 
               
               
                   
                 Rhinotracheitis (IBR) 
                   
                   
                   
               
               
                   
                 Bovine Viral Diarrhea 
                 BVD-1 
                 
                   Clostridium 
                 
                   
               
               
                   
                   
                 BVD-2 
                 
                   E. coli 
                 
                   
               
               
                   
                   
                   
                 
                   Streptococcus 
                 
                   
               
               
                   
                   
                   
                 
                   Staphylococcus 
                 
                   
               
               
                   
                   
                   
                 
                   Peptostreptococcus 
                 
                   
               
               
                 Porcine 
                 Swine Influenza 
                 Swine Influenza-A 
                 
                   Pasturella multocida 
                 
                 
                   Arcanobacterium 
                 
               
               
                   
                   
                   
                   
                 
                   pyogenes 
                 
               
               
                   
                   
                   
                   
                 
                   Haemophilus 
                 
               
               
                   
                 Inclusion Body Rhinitis 
                 Porcine Cytomegalovirus 
                 
                   Bordetella bronchiseptica 
                 
                   
               
               
                   
                 (Atrophic Rhinitis) 
                 (PCMV) 
                 
                   Pasturella multocida 
                 
                   
               
               
                   
                 Porcine Reproductive 
                 PRRSV 
                 
                   Streptococcus suis 
                 
                   
               
               
                   
                 and Respiratory Syndrome 
                   
                 
                   Haemophilus parasuis 
                 
                   
               
               
                   
                 (PRRS) 
                   
                 
                   Arcanobacterium suis 
                 
                   
               
               
                   
                   
                   
                 
                   E. coli 
                 
                   
               
               
                   
                 Transmissible 
                 TGEV 
                 
                   E. coli 
                 
                 
                   Streptococcus 
                 
               
               
                   
                 Gastroenteritis (TGE) 
                   
                 
                   Clostridium 
                 
                 
                   Staphlococcus 
                 
               
               
                 Equine 
                 Equine Influenza 
                 EIV-1 
                 
                   Streptococcus 
                 
                   
               
               
                   
                   
                 EIV-2 
                 
                   zooepidermicis 
                 
                   
               
               
                   
                   
                   
                 
                   Staphlococcus aureus 
                 
                   
               
               
                 Avian 
                   
                   
                   
                   
               
               
                 Chicken 
                 Infectious Bronchitis 
                 IBV 
                 Respiratory E. coli   
                   
               
               
                 Turkey 
                 Hemorrhagic Enteritis 
                 Adenovirus 
                 Enteropathic E. coli   
                   
               
               
                   
                   
                   
                 Enteropathic E. coli   
                   
               
               
                   
                 Poult Enteritis 
                 Coronavirus 
                 Enteropathic E. coli   
                   
               
               
                 Ovine 
                 Pneumonic Pasturellosis 
                 ORSV 
                 
                   Mannheimia haemolytica 
                 
                 
                   Pasturella multocida 
                 
               
               
                   
                   
                 Pi-3 
                   
                   
               
               
                   
                   
                 Adenovirus 
                   
                   
               
               
                   
                   
                 Reovirus 
               
               
                   
               
            
           
         
       
     
     Table 2 represents a partial list of infectious diseases in veterinary medicine known to be superinfections. Superinfections are those diseases requiring at least 2 different infectious microbes, that together produce a disease that neither are capable of doing alone. In these cases, one or more virus are associated with one or more neuraminidase dependent bacteria. 
     Feline Parvovirus and Upper Respiratory Complex and canine Parvoviral Enteritis and Tracheobronchitis have proven to be responsive to neuraminidase inhibitors. There is no reason, the other superinfections will not respond in the same manner. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Parvo Cases at Chihuahua Kennel 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Case 
                   
                   
                   
                   
                 IV 
                 Tamiflu 
                 Days to 
               
               
                 Number 
                 Town State 
                 Breed 
                 Age 
                 Parvo Test 
                 Drugs 
                 1 mg/lb 
                 Recover 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 1 
                 DC County Loving 
                 Chihuahua 
                 6 wks 
                 (+) 
                 Yes 
                 None 
                 Died 
               
               
                 2 
                 Kennel, Purdon, TX 
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 3 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 4 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 5 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 6 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 7 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 8 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 9 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 10 
                 Changed Veterinarian 
                 Chihuahua 
                 6 wks 
                 (+) 
                 None 
                 AM/PM 
                 5 
               
               
                 11 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 12 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 13 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 14 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 15 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 16 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 17 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 18 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 19 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 20 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 21 
                 Exposed—Preventive 
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 22 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 23 
                   
                 Chihuahua 
                 6 wks 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 24 
                   
                 Chihuahua 
                 Adult 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 25 
                   
                 Chihuahua 
                 Adult 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 26 
                   
                 Chihuahua 
                 Adult 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 27 
                   
                 Chihuahua 
                 Adult 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 28 
                   
                 Chihuahua 
                 Adult 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                   
               
            
           
         
       
     
     Table 3 represents 28 Chihuahua dogs and puppies that experienced an outbreak of canine parvoviral enteritis within their kennel. The initial treatment lasted one week and was consistent with traditional therapy. (IV fluids, antibiotics and antiemetics). During the first week, 9 puppies died and a second veterinarian was consulted. 
     The second veterinarian removed all IV treatment and started oral TAMIFLU and AmoxiDrops on 11 puppies. This treatment was administered by the kennel staff with the veterinarian consulting by phone. All puppies survived with the new protocol. 
     The exposed dogs received 1 mg/lb of TAMIFLU once a day for 5 days. Although exposed, these dogs remained healthy. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Canine Parvo Cases at Sandcastle Kennels 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Case 
                   
                   
                   
                 Parvo 
                 IV 
                 Tamiflu 
                 Days to 
               
               
                 Number 
                 Town State 
                 Breed 
                 Age 
                 Test 
                 Drugs 
                 1 mg/lb 
                 Recover 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Foyil Oklahoma 
                 Cocker 
                 6 
                 wk 
                 (+) 
                 Yes 
                 None 
                 Died 
               
               
                 2 
                   
                 Cocker 
                 6 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 3 
                   
                 Cocker 
                 6 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 4 
                   
                 Cocker 
                 6 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 5 
                   
                 Cocker 
                 6 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 6 
                   
                 Cocker 
                 8 
                 wk 
                 (+) 
                 Yes 
                 None 
                 Died 
               
               
                 7 
                   
                 Cocker 
                 8 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 8 
                   
                 Cocker 
                 8 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 9 
                   
                 Cocker 
                 8 
                 wk 
                 No 
                 Yes 
                 None 
                 Died 
               
               
                 10 
                 Changed Veterinarian 
                 Cocker 
                 6 
                 wk 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                 11 
                   
                 Cocker 
                 6 
                 wk 
                 No 
                 None 
                 AM/PM 
                 5 
               
               
                 12 
                   
                 Cocker 
                 8 
                 wk 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                 13 
                   
                 Cocker 
                 8 
                 wk 
                 No 
                 None 
                 AM/PM 
                 5 
               
               
                 14 
                   
                 Cocker 
                 8 
                 wk 
                 No 
                 Yes 
                 AM/PM 
                 5 
               
               
                 15 
                   
                 Cocker 
                 10 
                 wk 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                 16 
                   
                 Cocker 
                 11 
                 wk 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 17 
                   
                 Cocker 
                 12 
                 wk 
                 (+) 
                 None 
                 AM/PM 
                 4 
               
               
                 18 
                   
                 Cocker 
                 12 
                 wk 
                 No 
                 None 
                 AM/PM 
                 5 
               
               
                 19 
                   
                 Cocker 
                 12 
                 wk 
                 No 
                 None 
                 AM/PM 
                 3 
               
               
                 20 
                   
                 Cocker 
                 12 
                 wk 
                 (+) 
                 Yes 
                 AM/PM 
                 4 
               
               
                 21 
                   
                 Cocker 
                 14 
                 wk 
                 (+) 
                 None 
                 AM/PM 
                 5 
               
               
                 22 
                 Exposed—Preventive 
                 Cocker 
                 7 
                 month 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 23 
                   
                 Cocker 
                 7 
                 month 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 24 
                   
                 Cocker 
                 10 
                 month 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                 25 
                   
                 Cocker 
                 10 
                 month 
                 No 
                 None 
                 AM 
                 Healthy 
               
               
                   
               
            
           
         
       
     
     Table 4 represents of 25 cocker spaniel dogs and puppies that experienced an outbreak of canine parvoviral enteritis within their kennel. The initial treatment lasted one week and was consistent with traditional therapy consisting of IV fluids and antibiotics, antiemetics and steroids. During this period of time, 9 puppies died, and a second veterinarian was consulted. 
     The second veterinarian removed all IV treatment and oral TAMIFLU and sulfadimethoxine/ormetoprim (antibiotic) were the only drugs administered to 11 of the puppies. The 12th puppy was taken to the veterinarian&#39;s clinic and received IV therapy. Those puppies remaining at the kennel were treated by the kennel staff. 
     The exposed dogs received 1 mg/lb of TAMIFLU once a day for 5 days and did not develop canine parvoviral enteritis. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Canine Parvoviral Enteritis Treated With Tamiflu 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Case 
                   
                   
                   
                 Parvo 
                 IV 
                 Tamiflu 
                 Days to 
               
               
                 Number 
                 Town State 
                 Breed 
                 Age 
                 Test 
                 Drugs  
                 1 mg/lb 
                 Recover 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                  1-10 
                 Pinehurst, NC 
                 Mix 
                 6-12 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 3 to 5 
               
               
                 11 
                 Griffin, GA 
                 Mix 
                 11 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                 12 
                   
                 Mix 
                 14 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 13 
                   
                 Mix 
                 14 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 14 
                 Rockford, IL 
                 GSH 
                 8 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 15 
                 Clayton, NC 
                 JRT 
                 7 
                 months 
                 (+) 
                 Yes 
                 AM/PM 
                 5 
               
               
                 16 
                 Carthage, NC 
                 Mix 
                 19 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                 17 
                   
                 Mix 
                 20 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 4 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 18 
                 Apple Valley, CA 
                 Beagle 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 19 
                 Millington, TN 
                 GSH 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 20 
                 Douglas, GA 
                 Basset 
                 12 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 21 
                   
                 It. Greyh. 
                 12 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 22 
                   
                 Boxer 
                 12 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 23 
                 Canton, OH 
                 Rotti-x 
                 6 
                 months 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 24 
                 Griffin, GA 
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 25 
                   
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 26 
                   
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 27 
                 Salisbury, MD 
                 Pit Bull-x 
                 6 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 2 
               
               
                 28 
                 Redford, MI 
                 Pit Bull 
                 9  
                 months 
                 Corona 
                 Yes 
                 AM/PM 
                 4 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 29 
                 Grand Rapids, MI 
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 30 
                   
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 31 
                   
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 32 
                 Bend, OR 
                 Bost. Terr. 
                 6 
                 months 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 33 
                 Mishawaka, IN 
                 Eng. Sett. 
                 14 
                 wks 
                 None 
                 Yes 
                 AM/PM 
                 4 
               
               
                 34 
                 Vancouver, WA 
                 Rotti 
                 8 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 5 
               
               
                 35 
                 Atlanta, GA 
                 Mix 
                 7 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 36 
                 Jonesboro, AR 
                 Min. Sch. 
                 6 
                 months 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 37 
                   
                 Beagle-x 
                 5 
                 months 
                 (+) 
                 Yes 
                 AM/PM 
                 4 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 38 
                 Columbia, MO 
                 Mix 
                 Pup 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 39 
                 Ocoee, FL 
                 Shar Pei 
                 4 
                 months 
                 (+) 
                 None 
                 AM/PM 
                 2 
               
               
                 40 
                 Mishawaka, IN 
                 Mix 
                 14 
                 wks 
                 (weak) 
                 Yes 
                 AM/PM 
                 4 
               
               
                 41 
                   
                 Mix 
                 4 
                 months 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 42 
                   
                 Mix 
                 12 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 43 
                 Atlanta, GA 
                 Mix 
                 10 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                 44 
                   
                 Gold. Ret. 
                 8 
                 wks 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 45 
                 Los Angeles, CA 
                 St. Ber. mix 
                 10 
                 wks 
                 (+) 
                 None 
                 AM/PM 
                 2 
               
               
                 46-48 
                 Garden City, KS 
                 Lab 
                 6 
                 months 
                 (+) 
                 None 
                 AM/PM 
                 3 
               
               
                   
                 (exposed) 
                 B. CollieX 
                 12 
                 weeks 
                 (weak) 
                 None 
                 AM/PM 
                 Normal 
               
               
                   
                   
                 B. CollieX 
                 12 
                 weeks 
                 (+) 
                 None 
                 AM/PM 
                 4 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Summary: 
                   
                   
               
               
                 States 
                 15 
                   
               
               
                 DVMS 
                 20 
                   
               
               
                 Puppies 
                 48 
                   
               
            
           
         
       
     
     Table 5 represents 48 individual cases of Canine Parvoviral Enteritis treated with 1 mg/lb TAMIFLU AM/PM for 10 treatments. Cases posted VIN&#39;s Infectious Dz Board by 20 veterinarians practicing in 15 states. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Feline Parvoenteritis Treated with Tamiflu 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Case 
                   
                   
                   
                 Parvo 
                 IV 
                 Tamiflu 
                 Days to 
               
               
                 Number 
                 Town State 
                 Breed 
                 AgeSex 
                 Test 
                 Drugs 
                 1 mg/lb  
                 Recover 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 Smithfield, NC 
                 Siamese 
                 5 
                 M/m 
                 (+) 
                 Yes 
                 AM/PM 
                 2 
               
               
                 2 
                   
                 Siamese 
                 5 
                 M/fem 
                 (+) 
                 Yes 
                 AM/PM 
                 3 
               
               
                 3 
                 Alberta, Canada 
                 DSH 
                 14 
                 wk/m 
                 no WBCs 
                 Yes 
                 AM/PM 
                 3 
               
               
                 4 
                 (Exposed) 
                 DSH 
                 20 
                 wk/fem 
                 condomate 
                 None 
                 AM 
                 Normal 
               
               
                 5 
                 Phoenix, AZ 
                 DSH 
                 10 
                 wk/fem 
                 (+) 
                 SQ fluids 
                 AM/PM 
                 4 
               
               
                 6 
                   
                 DSH 
                 10 
                 wk/fem 
                 (+) 
                 SQ fluids 
                 AM/PM 
                 4 
               
               
                   
               
            
           
         
       
     
     Table 6 represents 5 cases of Feline Parvoviral Enteritis with TAMIFLU at 1 mg/lb AM/PM for 10 treatments. One kitten exposed, remained normal when given TAMIFLU at 1 mg/lb once a day for 5 days. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Raccoon Parvoenteritis/Distemper Treated with Tamiflu 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Case 
                   
                   
                   
                   
                   
                 Tamiflu 
                 Days to 
               
               
                 Number 
                 Town State 
                 Breed 
                 Age 
                 Parvo Test 
                 IV Drugs 
                 1 mg/lb 
                 Recover 
               
               
                   
               
               
                 1 
                 Hudson, IL 
                 Raccoon 
                 Adult/Male 
                 none 
                 none 
                 AM/PM 
                 3 
               
               
                 2 
                   
                 Raccoon 
                 Adult/Fem 
                 none 
                 none 
                 AM/PM 
                 3 
               
               
                 3 
                 Chiefland, FL 
                 Raccoon 
                 Adult 
                 none 
                 none 
                 AM/PM 
                 3 
               
               
                 4 
                   
                 Raccoon 
                 Adult 
                 none 
                 none 
                 AM/PM 
                 3 
               
               
                 5 
                   
                 Raccoon 
                 Adult 
                 none 
                 none 
                 AM/PM 
                 3 
               
               
                   
               
            
           
         
       
     
     Table 7 represents 5 raccoons treated with TAMIFLU at 1 mg/lb given every 12 hrs for 10 treatments. Treatment administered by civilian rehabbers at their homes. Granules mixed with pancake syrup. 
     Raccoons represent the 5th species (cow, dog, cat, mice) in which a neuraminidase inhibitor has been successful in treating or preventing a disease associated with neuraminidase dependent bacteria. Before using TAMIFLU, the hemorrhagic gastroenteritis (Parvo) in raccoon was 100% fatal. While the numbers are small they are significant as they prove the pathobiology seen in hemorrhagic gastroenteritis of raccoon is neuraminidase driven. Treatment was administered by untrained lay personnel at the rehab centers. 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Canine Kennel Cough Cases Treated With Tamiflu 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Case 
                   
                   
                   
                   
                 Oral 
                 Cough 
                 Tamiflu 
                 Days to 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Number 
                 Town State 
                 Breed 
                 Age 
                 Antibiotic 
                 Suppressant 
                 AM/PM 
                 Recover 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Holding Kennels for Pet Stores 
                 1 mg/lb 
                   
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                  1-175 
                 Lynbrook, NY 
                 Mixed 
                 8-12 
                 wks 
                 Doxy 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                 1-65 
                 New Hyde Park, NY 
                 Mixed 
                 8-12 
                 wks 
                 Doxy 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                 1-60 
                 Lawrence, NY 
                 Mixed 
                 8-12 
                 wks 
                 Doxy 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Racing Greyhounds at Race Tracks 
                 1 mg/lb 
                   
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1, 2, 3 
                 Miami, Florida 
                 Greyhound 
                 1.5-4 
                 yr. 
                 None 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                 1-46 
                 Group A 
                 Greyhound 
                 1.5-4 
                 yr. 
                 Doxy 
                 Dextromet 
                 none 
                 No Change 
               
               
                 1-46 
                 Group B 
                 Greyhound 
                 1.5-4 
                 yr. 
                 Cephalexin 
                 Torbutrol 
                 none 
                 No Change 
               
               
                 1-47 
                 Group C 
                 Greyhound 
                 1.5-4 
                 yr. 
                 Clamamox 
                 Hycodan 
                 none 
                 No Change 
               
            
           
           
               
            
               
                 ***After 5 days, DVM stopped antibiotics and cough suppressants and started Tamiflu 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1-46 
                 Group A 
                 Greyhound 
                 1.5-4 
                 yr. 
                 None 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                 1-46 
                 Group B 
                 Greyhound 
                 1.5-4 
                 yr. 
                 None 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                 1-47 
                 Group C 
                 Greyhound 
                 1.5-4 
                 yr. 
                 None 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                 1-70 
                 Kan. City, Kansas 
                 Greyhound 
                 1.5-4 
                 yr. 
                 Doxy 
                 None 
                 AM/PM 
                 3-5 days 
               
               
                   
               
            
           
           
               
               
               
            
               
                 ***Track Veterinarian had to use 0.5 mg/lb due to cost 
                 0.5 mg/lb   
                   
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 1-72 
                 Mobile, Alabama 
                 Greyhound 
                 11.5-4 
                 yr. 
                 Pen—G 
                 None 
                 (+) 
                 5-10 days  
               
               
                   
               
            
           
         
       
     
     Infectious Canine Tracheobronchitis (ICT) or Kennel Cough is a highly infectious superinfection spread by aerosol droplets. The 3 holding kennels represent the first attempt at a herd health plan. The sick dogs were given TAMIFLU at 1 mg/lb AM/PM for 5 days. They recovered in 3-5 days. Those not showing clinical signs and any new puppy entering the kennel were given 1 mg/lb once a day for 5 days. This program reduced illness to below 5 percent, and cost of veterinary care by over 75%. 
     Kennel Cough outbreaks at Greyhound racing tracks result in the tracks being closed. In Miami, a total of 142 dogs became infected with ICT. They were separated into 4 groups: Group A, B and C received a different combination of antibiotic/cough suppressant. Three dogs were given TAMIFLU at 1 mg/lb AM/PM for 10 treatments. Groups A, B and C&#39;s clinical course was unchanged after 5 days of conventional therapy. Started TAMIFLU, and dogs recovered in 3-5 days. 
     The Miami experiment was the basis for treatment during a similar ICT outbreak at a Kansas City track. 
     Cost of TAMIFLU was a factor during an ITC outbreak in Mobil, Ala. They The DVM decided to give half the recommended dose (0.5 mg/lb). The results were better than conventional, but longer than when the recommended dose is used. This trial demonstrates that the response is dose related. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Canine Diseases 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinomyces 
                 
                 Pyothorax 
                   
                   
                 Deep Wounds 
               
               
                   
                 Peritonitis 
                   
                   
                   
               
               
                 
                   Aeromonas 
                 
                   
                   
                   
                 Septicemia 
               
               
                 
                   Bacteroides 
                 
                   
                   
                   
                 Bone Infect. 
               
               
                 
                   Bordetella 
                 
                 Kennel Cough 
                   
                   
                   
               
               
                   
                 Distemper 
                   
                   
                   
               
               
                   
                 Upper Resp. Infect. 
                   
                   
                   
               
               
                 
                   Brucella 
                 
                   
                 Abortion 
                   
                   
               
               
                   
                   
                 Infertility 
                   
                   
               
               
                 
                   Campylobacter 
                 
                   
                   
                 Gastroenteritis 
                   
               
               
                 
                   Clostridium 
                 
                   
                   
                 Gastroenteritis 
                 Tetnus 
               
               
                   
                   
                   
                 Parvoenteritis 
                 Botulism 
               
               
                 
                   Corynebacterium 
                 
                   
                   
                   
                   
               
               
                 
                   Enterobacter 
                 
                   
                   
                   
                   
               
               
                 
                   E. coli 
                 
                 Upper Respiratory 
                 Pyometra 
                 Colibacillosis 
                   
               
               
                   
                 Pneumonia 
                 Mastitis 
                 Parvoenteritis 
                   
               
               
                   
                   
                 Renal Infections 
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Erysipelothrix 
                 
                   
                   
                   
                 Endocarditis 
               
               
                 
                   Fusobacterium 
                 
                   
                   
                   
                   
               
               
                 
                   Klebsiella 
                 
                 Upper Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                   
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Pasturella 
                 
                 Upper Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                   
                   
                   
               
               
                 
                   Peptostreptococcus 
                 
                   
                   
                   
                 Abscesses 
               
               
                 
                   Proteus 
                 
                   
                 Upper and Lower 
                 Gastroenteritis 
                 Otitis 
               
               
                   
                   
                 Urinary Tract 
                   
                   
               
               
                 
                   Pseudomonas 
                 
                 Upper Respiratory 
                 Pyometra 
                   
                 Otitis 
               
               
                   
                 Pneumonia 
                 Cystitis 
                   
                 Dermatitis 
               
               
                 
                   Rhodococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Salmonella 
                 
                   
                   
                 Gastroenteritis 
                   
               
               
                 
                   Serratia 
                 
                   
                   
                   
                   
               
               
                 
                   Shigella 
                 
                   
                   
                 Gastroenteritis 
                   
               
               
                 
                   Staphlococci 
                 
                 Upper Respiratory 
                 Pyometra 
                   
                 Otitis 
               
               
                   
                 Pneumonia 
                 Mastitis 
                   
                 Dermatitis 
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Streptococci 
                 
                 Pneumonia 
                 Pyometra 
                 Parvoenteritis 
                 Septicemia 
               
               
                   
                   
                 Mastitis 
                   
                 Puppy Strangles 
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Haemophilus 
                 
                   
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
               
               
                   
               
            
           
         
       
     
     Table 9 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated with them in the dog. 
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Feline Diseases 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinomyces 
                 
                 Pyothorax 
                   
                   
                 Abscess 
               
               
                   
                 Peritonitis 
                   
                   
                   
               
               
                 
                   Aeromonas 
                 
                   
                   
                   
                   
               
               
                 
                   Bacteroides 
                 
                 Emphyema 
                   
                   
                 Abscess 
               
               
                 
                   Bordetella 
                 
                 Upper  
                   
                   
                   
               
               
                   
                 Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                   
                   
                   
               
               
                 
                   Brucella 
                 
                   
                   
                   
                   
               
               
                 
                   Campylobacter 
                 
                   
                   
                 Gastroenteritis 
                   
               
               
                 
                   Clostridium 
                 
                   
                   
                 Gastroenteritis 
                 Tetnus 
               
               
                   
                   
                   
                 Panleukopenia 
                   
               
               
                 
                   Corynebacterium 
                 
                   
                   
                   
                   
               
               
                 
                   Enterobacter 
                 
                   
                   
                   
                   
               
               
                 
                   E. coli 
                 
                   
                 Pyometra 
                 Colibacillosis 
                   
               
               
                   
                   
                 Mastitis 
                 Panleukopenia 
                   
               
               
                   
                   
                 Renal  
                   
                   
               
               
                   
                   
                 Infections 
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Erysipelothrix 
                 
                   
                   
                   
                   
               
               
                 
                   Fusobacterium 
                 
                   
                   
                   
                   
               
               
                 
                   Klebsiella 
                 
                 Upper  
                   
                   
                   
               
               
                   
                 Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                   
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Pasturella 
                 
                 Upper  
                   
                   
                   
               
               
                   
                 Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                   
                   
                   
               
               
                   Peptostrepto - 
                   
                   
                   
                   
               
               
                 
                   coccus 
                 
                   
                   
                   
                   
               
               
                 
                   Proteus 
                 
                   
                   
                   
                 Otitis 
               
               
                 
                   Pseudomonas 
                 
                 Upper  
                 Pyometra 
                   
                 Otitis 
               
               
                   
                 Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                 Cystitis 
                   
                 Abscess 
               
               
                 
                   Rhodococcus 
                 
                 Pyothorax 
                   
                   
                 Abscess 
               
               
                 
                   Salmonella 
                 
                   
                   
                 Gastroenteritis 
                   
               
               
                 
                   Serratia 
                 
                   
                   
                   
                   
               
               
                 
                   Shigella 
                 
                   
                   
                 Gastroenteritis 
                   
               
               
                 
                   Staphlococci 
                 
                 Upper  
                 Pyometra 
                   
                 Otitis 
               
               
                   
                 Respiratory 
                   
                   
                   
               
               
                   
                 Pneumonia 
                 Mastitis 
                   
                 Dermatitis 
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Streptococci 
                 
                 Pneumonia 
                 Pyometra 
                 Panleukopenia 
                 Septicemia 
               
               
                   
                   
                 Mastitis 
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Haemophilus 
                 
                   
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
               
               
                   
               
            
           
         
       
     
     Table 10 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated with them in the cat. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Bovine Diseases 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinomyces 
                 
                 Pneumonia 
                 Mastitis 
                   
                 “Lumpy Jaw” 
               
               
                   
                   
                 Endometritis 
                   
                 Arthritis 
               
               
                   
                   
                 Umbilical Infections 
                   
                 Endocarditis 
               
               
                   
                   
                 Seminal Vesiculitis 
                   
                 Abscess 
               
               
                 
                   Aeromonas 
                 
                   
                 Mastitis 
                   
                   
               
               
                 
                   Bacteroides 
                 
                   
                 Mastitis 
                 Gastroenteritis 
                 Foot Rot 
               
               
                   
                   
                   
                   
                 Osteomyelitis 
               
               
                 
                   Brucella 
                 
                   
                 Abortion 
                   
                   
               
               
                   
                   
                 Orchitis 
                   
                   
               
               
                 
                   Campylobacter 
                 
                   
                 Epizootic Infertility 
                   
                   
               
               
                   
                   
                 Embryonic Death 
                   
                   
               
               
                   
                   
                 Abortion 
                   
                   
               
               
                 
                   Clostridium 
                 
                   
                 Gangrenous Mastitis 
                 Enterotoxaemia 
                 Tetanus 
               
               
                   
                   
                   
                   
                 Botulism 
               
               
                   
                   
                   
                   
                 Blackleg 
               
               
                   
                   
                   
                   
                 Malignant Edema 
               
               
                   
                   
                   
                   
                 Gas Gangrene 
               
               
                   
                   
                   
                   
                 Bacillary Haemoglobinuria 
               
               
                 
                   Corynebacterium 
                 
                   
                 Pyelonephritis 
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                   
                   
                 Mastitis 
                   
                   
               
               
                 
                   Enterobacter 
                 
                   
                 Coliform Mastitis 
                   
                   
               
               
                 
                   E. coli 
                 
                   
                 Mastitis 
                 “White Scours” 
                 Septicemia 
               
               
                   
                   
                   
                 Colibacillosis 
                 Joint III 
               
               
                 
                   Fusobacterium 
                 
                 Calf Diphtheria 
                 Mastitis 
                 Liver Abscess in Feedlot 
                   
               
               
                   
                   
                 Metritis 
                 Hepatic Necrobacillosis 
                   
               
               
                 
                   Klebsiella 
                 
                   
                 Mastitis 
                   
                   
               
               
                 
                   Pasturella 
                 
                 “Shipping Fever ” 
                   
                   
                 Hemorrhagic 
               
               
                   
                 “Enzootic Pneumonia” 
                   
                   
                 Septicemia 
               
               
                   
                   
                   
                   
                 Fibrogranulomatous Disease 
               
               
                 
                   Peptostreptococcus 
                 
                   
                 Summer Mastitis 
                   
                   
               
               
                 
                   Proteus 
                 
                   
                   
                 Enteritis 
                   
               
               
                 
                   Pseudomonas 
                 
                 Focal Pneumonia 
                 Mastitis 
                 Enteritis 
                 Dermatitis 
               
               
                   
                   
                 Uterine Infections 
                   
                 Abscess 
               
               
                   
                   
                   
                   
                 Arthritis 
               
               
                 
                   Salmonella 
                 
                   
                 Abortion 
                 Enteritis 
                 Septicaemia 
               
               
                   
                   
                   
                   
                 Meningitis 
               
               
                   
                   
                   
                   
                 Joint III 
               
               
                   
                   
                   
                   
                 Dry Gangrene 
               
               
                 
                   Serratia 
                 
                   
                 Mastitis 
                   
                 in Calves 
               
               
                 
                   Staphlococci 
                 
                   
                 Mastitis 
                   
                   
               
               
                   
                   
                 Udder impetigo 
                   
                   
               
               
                 
                   Streptococci 
                 
                   
                 Mastitis/Metritis 
                   
                   
               
               
                 
                   Haemophilus 
                 
                 Pneumonia 
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
                 Pneumonia 
                 Mastitis 
                 Liver Abscess 
                 Foot Rot 
               
               
                   
               
            
           
         
       
     
     Table 11 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated with them in the cow. 
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Porcine Diseases 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinomyces 
                 
                 Pneumonia 
                 Pyogranulomatous 
                   
                 Arthritis 
               
               
                   
                   
                 Mastitis 
                   
                 Lymphadenitis 
               
               
                   
                   
                 Endometritis 
                   
                   
               
               
                   
                   
                 Umbilical Infections 
                   
                   
               
               
                   
                   
                 Seminal Vesiculitis 
                   
                   
               
               
                 
                   Aeromonas 
                 
                   
                   
                 Diarrhea 
                   
               
               
                 
                   Bacteroides 
                 
                   
                   
                 Diarrhea in Piglets 
                 Abscess 
               
               
                 
                   Bordetella 
                 
                 Atrophic Rhinitis 
                   
                   
                   
               
               
                   
                 Bronchopneumonia in  
                   
                   
                   
               
               
                   
                 Young Piglets 
                   
                   
                   
               
               
                 
                   Brucella 
                 
                   
                 Abortion 
                   
                 Arthritis 
               
               
                   
                   
                 Orchitis 
                   
                 Spondylitis 
               
               
                   
                   
                 Infertility 
                   
                   
               
               
                 
                   Campylobacter 
                 
                   
                 Intestinal Adenomatosis 
                 Diarrhea 
                   
               
               
                 
                   Clostridium 
                 
                   
                   
                   
                 Tetnus 
               
               
                   
                   
                   
                   
                 Botulinum 
               
               
                   
                   
                   
                   
                 Black Leg 
               
               
                   
                   
                   
                   
                 Maligant Edema 
               
               
                   
                   
                   
                   
                 Hemorrhagic Enterotoxemia 
               
               
                 
                   Corynebacterium 
                 
                   
                 Pyelonephritis 
                   
                   
               
               
                 
                   Enterobacter 
                 
                   
                 Mastitis-Metritis 
                   
                   
               
               
                   
                   
                 Agalactia Complex(MMA) 
                   
                   
               
               
                 
                   E. coli 
                 
                 Associated with PRRSV 
                 Mastitis 
                 Neonatal Diarrhea 
                 Piglet 
               
               
                   
                   
                 Mastitis-Metritis 
                 Colisepticemia 
                 Meningitis 
               
               
                   
                   
                 Agalactia Complex(MMA) 
                 Weaning Enteritis 
                 Sudden 
               
               
                   
                   
                   
                   
                 Edema/death 
               
               
                 
                   Erysipelothrix 
                 
                   
                 Acute Abortion 
                   
                 “Diamond Skin Disease” 
               
               
                   
                   
                   
                   
                 Vegetative Endocarditis 
               
               
                   
                   
                   
                   
                 Polyarthritis 
               
               
                 
                   Fusobacterium 
                 
                 “Bull-Nose” 
                   
                 Necrotic Enteritis 
                 Liver Abscess 
               
               
                 
                   Pasturella 
                 
                 Pneumonia Assoc. w/PRRSV 
                   
                   
                   
               
               
                   
                 Atrophic Rhinitis 
                   
                   
                   
               
               
                 
                   Peptostreptococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Pseudomonas 
                 
                 Respiratory Infections 
                 Abortion 
                 Enteritis 
                 Otitis 
               
               
                   
                   
                   
                   
                 Arthritis 
               
               
                 
                   Rhodococcus 
                 
                   
                   
                   
                 Cervical Lymphadenitis 
               
               
                 
                   Salmonella 
                 
                   
                   
                 Hog Cholera 
                   
               
               
                   
                   
                   
                 Chronic Enteritis 
                 Septicemia 
               
               
                 
                   Serpulina 
                 
                   
                   
                 Swine Dysentery 
                   
               
               
                 
                   Staphlococci 
                 
                   
                 Mastitis 
                   
                 Exudative Epidermitis or 
               
               
                   
                   
                 Endometritis 
                   
                 Greasy Pig Disease 
               
               
                   
                   
                 Udder Impetigo 
                   
                   
               
               
                 
                   Streptococci 
                 
                 Rhinitis, Pneumonia 
                   
                   
                 Lymphadenitis 
               
               
                   
                 assoc. w/Porcine Reproductive  
                   
                   
                 Arthritis 
               
               
                   
                 and Respiratory Syndrome 
                   
                   
                   
               
               
                 
                   Haemophilus influenzae 
                 
                 Porcine Reproductive and  
                   
                   
                   
               
               
                   
                 Respiratory Syndrome 
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
                 Pneumonia 
               
               
                   
               
            
           
         
       
     
     Table 12 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated with them in the pig. 
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Equine Diseases 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinomyces 
                 
                   
                   
                   
                 Poll Evil 
               
               
                   
                   
                   
                   
                 Fistulous Withers 
               
               
                 
                   Aeromonas 
                 
                   
                   
                   
                   
               
               
                 
                   Bacteroides 
                 
                   
                   
                 Diarrhea in Foals 
                 Osteomylitis 
               
               
                   
                   
                   
                   
                 Buccal Cavity Lesions 
               
               
                 
                   Bordetella 
                 
                 Respiratory Infections 
                   
                   
                   
               
               
                 
                   Brucella 
                 
                   
                   
                   
                 Poll Evil 
               
               
                   
                   
                   
                   
                 Fistulous Withers 
               
               
                 
                   Campylobacter 
                 
                   
                   
                   
                   
               
               
                 
                   Clostridium 
                 
                   
                   
                 Enteritis 
                 Tetanus 
               
               
                   
                   
                   
                   
                 Botulism 
               
               
                 
                   Corynebacterium 
                 
                   
                   
                   
                 Ulcerative Lymphangitis 
               
               
                 
                   Enterobacter 
                 
                   
                 Metritis 
                   
                   
               
               
                 
                   E. coli 
                 
                   
                   
                 Enteritis 
                   
               
               
                 
                   Erysipelothrix 
                 
                   
                   
                   
                   
               
               
                 
                   Fusobacterium 
                 
                   
                   
                   
                 “Thrush” involving the frog 
               
               
                 
                   Klebsiella 
                 
                 Pneumonia in Foals 
                 Metritis 
                   
                 Abscess 
               
               
                   
                   
                 Cervicitis 
                   
                   
               
               
                 
                   Pasturella 
                 
                 Respiratory Infections 
                   
                   
                   
               
               
                   
                 Pneumonia 
                   
                   
                   
               
               
                 
                   Peptostreptococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Proteus 
                 
                   
                 Kidney infections 
                   
                   
               
               
                   
                   
                 Cystitis 
                   
                   
               
               
                 
                   Pseudomonas 
                 
                 Lung Abscesses 
                 Metritis 
                   
                 Eye Infections 
               
               
                   
                 Glanders 
                   
                   
                 Lymphangitiswith ulcers 
               
               
                   
                   
                   
                   
                 along lymphatics(Farcy) 
               
               
                 
                   Rhodococcus 
                 
                 Bronchopneumonia 
                   
                   
                   
               
               
                 
                   Salmonella 
                 
                   
                 Abortion 
                 Sever Enteritis 
                 Septicemia 
               
               
                 
                   Serratia 
                 
                   
                   
                   
                   
               
               
                 
                   Shigella 
                 
                   
                   
                   
                   
               
               
                 
                   Staphlococci 
                 
                   
                 Mastitis 
                   
                   
               
               
                   
                   
                 Botryomycosis after 
                   
                   
               
               
                   
                   
                 Castration 
                   
                   
               
               
                 
                   Streptococci 
                 
                 Pneumonia 
                 Endometritis 
                   
                 Foal Lymphangitis 
               
               
                   
                   
                 Mastitis 
                   
                 Abscess 
               
               
                   
                   
                 Abortion 
                   
                 Strangles 
               
               
                   
                   
                 Navel Infections 
                   
                 Purpura Hemorrhagica 
               
               
                   
                   
                 Genital Infections 
                   
                   
               
               
                 
                   Haemophilus 
                 
                   
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
               
               
                   
               
            
           
         
       
     
     Table 13 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated with them in the horse. 
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Avian Diseases 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinobacillus 
                 
                   
                   
                   
                   
               
               
                 
                   Actinomyese 
                 
                   
                   
                   
                   
               
               
                 
                   Aeromonas 
                 
                   
                   
                   
                 Septicemia 
               
               
                 
                   Bacteroides 
                 
                   
                   
                   
                   
               
               
                 
                   Bordetella 
                 
                 Turkey Coryza 
                   
                   
                   
               
               
                   
                 Rhinotracheitis 
                   
                   
                   
               
               
                   
                 Sinusitis 
                   
                   
                   
               
               
                 
                   Campylobacter 
                 
                   
                   
                 Avian Vibrionic Hepatitis 
                   
               
               
                 
                   Clostridium 
                 
                   
                   
                 Necrotic Enteritis 
                 Tetanus 
               
               
                   
                   
                   
                 Ulcerative Enteritis 
                 Botulism 
               
               
                   
                   
                   
                   
                 Necrotic Dermatitis 
               
               
                   
                   
                   
                   
                 “Struck” 
               
               
                 
                   Corynebacterium 
                 
                   
                   
                   
                   
               
               
                 
                   Enterobacter 
                 
                   
                   
                   
                   
               
               
                 
                   E. coli 
                 
                 Airsacculitis 
                 Ovarian Infection 
                 Peritonitis 
                 Omphalitis 
               
               
                   
                 Infectious Bronchitis 
                   
                 Hemorrhagic Enteritis 
                   
               
               
                   
                   
                   
                 Turkey Poult Enteritis 
                   
               
               
                   
                   
                   
                 Colibacillosis 
                   
               
               
                   
                   
                   
                 Coligranuloma in liver 
                   
               
               
                   
                   
                   
                 and intestines 
                   
               
               
                 
                   Erysipelothrix 
                 
                   
                   
                   
                 Spleenitis 
               
               
                   
                   
                   
                   
                 Endocarditis 
               
               
                   
                   
                   
                   
                 Arthritis 
               
               
                 
                   Fusobacterium 
                 
                 Avian Diphtheria secondary  
                   
                   
                   
               
               
                   
                 to Fowl Pox 
                   
                   
                   
               
               
                 
                   Klebsiella 
                 
                   
                   
                   
                   
               
               
                 
                   Pasturella 
                 
                 Fowl Plague 
                   
                 Fowl Cholera 
                 Fibrinous 
               
               
                   
                 Pasteurellosis 
                   
                   
                 Polyserositis 
               
               
                 
                   Peptostreptococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Proteus 
                 
                   
                   
                   
                   
               
               
                 
                   Pseudomonas 
                 
                   
                   
                   
                   
               
               
                 
                   Rhodococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Salmonella 
                 
                   
                   
                 Pullorum Disease 
                 Fowl 
               
               
                   
                   
                   
                 White Diarrhea 
                 Typhoid 
               
               
                   
                   
                   
                   
                 Paratyphoid 
               
               
                 
                   Serratia 
                 
                   
                   
                   
                 Septicemia 
               
               
                 
                   Staphlococci 
                 
                   
                   
                   
                 Bumble-Foot 
               
               
                   
                   
                   
                   
                 Arthritis 
               
               
                   
                   
                   
                   
                 Breast Blister 
               
               
                 
                   Streptococci 
                 
                   
                   
                   
                 Septisemia 
               
               
                   
                   
                   
                   
                 Endocarditis 
               
               
                 
                   Vibrio 
                 
                   
                   
                 Cholera-like Enteric Disease 
                   
               
               
                 
                   Haemophilus 
                 
                 Infectious Coryza 
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
               
               
                   
               
            
           
         
       
     
     Table 14 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated with them in chickens, turkeys, ducks. 
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Neuraminidase Dependent Bacteria and Other Species&#39; Diseases  
               
               
                 Sheep, Goats and Rabbits 
               
            
           
           
               
               
               
               
               
            
               
                 Bacteria spp: 
                 Respiratory 
                 Urogenital 
                 Gastrointestinal 
                 Other 
               
               
                   
               
               
                 
                   Actinomyces 
                 
                   
                   
                   
                   
               
               
                 
                   Aeromonas 
                 
                   
                   
                   
                   
               
               
                 
                   Bacteroides 
                 
                   
                   
                   
                 Contagious Foot Rot 
               
               
                   
                   
                   
                 Enterotoxic Diarrhea 
                   
               
               
                 
                   Bordetella 
                 
                 “Snuffles” in Rabbits 
                   
                   
                   
               
               
                   
                 Bronchopneumonia 
                   
                   
                 Septicemia 
               
               
                 
                   Brucella 
                 
                   
                 Abortion 
                   
                   
               
               
                   
                   
                 Epididymitis 
                   
                   
               
               
                 
                   Campylobacter 
                 
                   
                 Abortion 
                   
                   
               
               
                   
                   
                 Ovine Genital  
                   
                   
               
               
                   
                   
                 Campylobacteriosis 
                   
                   
               
               
                 
                   Clostridium 
                 
                   
                 Pulpy Kidney Disease 
                 Enterotoxemia 
                 Tetanus 
               
               
                   
                   
                 Gangrenous Mastitis 
                 Mucoid Enteritis/Rabbits 
                 Botulism 
               
               
                   
                   
                   
                   
                 Maligant Edema 
               
               
                   
                   
                   
                 Braxy 
                 Big Head 
               
               
                   
                   
                   
                   
                 Hemorrhagic Enterotoxemia 
               
               
                   
                   
                   
                   
                 Struck 
               
               
                 
                   Corynebacterium 
                 
                   
                   
                   
                 Caseous Lymphadenitis 
               
               
                 
                   Enterobacter 
                 
                   
                   
                   
                   
               
               
                 
                   E. coli 
                 
                   
                 Mastitis 
                 Colibacillosis 
                   
               
               
                   
                   
                   
                 Colisepticemia 
                   
               
               
                   
                   
                   
                 “Watery Mouth” in Nenatal  
                   
               
               
                   
                   
                   
                 Lambs 
                   
               
               
                 
                   Erysipelothrix 
                 
                   
                   
                   
                 Septicemia 
               
               
                   
                   
                   
                   
                 Arthritis 
               
               
                   
                   
                   
                   
                 Endocarditis 
               
               
                 
                   Fusobacterium 
                 
                   
                   
                   
                 Foot Abscess 
               
               
                   
                   
                   
                   
                 Necrobacillosis of lips and  
               
               
                   
                   
                   
                   
                 mouth 
               
               
                 
                   Klebsiella 
                 
                   
                   
                   
                   
               
               
                 
                   Pasturella 
                 
                 Pleuropneumonia 
                 Mastitis 
                   
                 Septicemia 
               
               
                 
                   Peptostreptococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Proteus 
                 
                   
                   
                 Diarrhea in Goats. Lambs 
                   
               
               
                 
                   Pseudomonas 
                 
                   
                   
                   
                 Arthritis 
               
               
                   
                   
                   
                   
                 Lymphangitis 
               
               
                 
                   Rhodococcus 
                 
                   
                   
                   
                   
               
               
                 
                   Salmonella 
                 
                   
                 Abortion in Ewes 
                 Enteritis 
                 Septicemia 
               
               
                 
                   Serratia 
                 
                   
                   
                   
                   
               
               
                 
                   Shigella 
                 
                   
                   
                   
                   
               
               
                 
                   Staphlococci 
                 
                   
                 Mastitis 
                   
                 Dermatitis 
               
               
                   
                   
                   
                   
                 Abscess 
               
               
                   
                   
                   
                   
                 Periorbital Eczema 
               
               
                   
                   
                   
                   
                 Conjunctivitis 
               
               
                 
                   Streptococci 
                 
                 Pneumonia 
                 Chronic Mastitis 
                   
                 Arthritis 
               
               
                 
                   Haemophilus 
                 
                   
                   
                   
                   
               
               
                 
                   Arcanobacterium 
                 
                   
                 Mastitis 
                   
                 Foot Abscess 
               
               
                   
               
            
           
         
       
     
     Table 15 is a partial listing of known neuraminidase dependent bacteria and the infectious diseases associated in sheep, goats, rabbits. 
     
       
         
           
               
             
               
                 TABLE 16 
               
               
                   
               
               
                 Clinical Trial: Tamiflu and  E. coli   
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Veterinarian or Clinic:  
                   
                 Cat Health Clinic 
                   
                 Phone: 
                 ( 910 ) 295-2287 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Address:  
                 2212 Midland Road 
                   
                 Pinehurst 
                   
                 NC 
                 28374 
               
               
                   
                   
                 Street 
                   
                 City 
                   
                 State 
                 Zip 
               
            
           
           
               
               
               
               
               
               
            
               
                 Patient: 
                 Owner:  
                 Vince and Peggy Meads 
                   
                   
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Name: 
                 Pinga 
                 Age:  
                 Oct. 19, 1998 
                 Breed: Siamese 
               
               
                   
                   
                   
                 Sex:  
                 FS 
                   
               
            
           
           
               
               
            
               
                 Medical History: 
                   
               
            
           
           
               
            
               
                 Presented Nov. 22, 2004 for vomiting beginning on Nov. 19, 2004. Blood for CBC/Chem Profile submitted along with 
               
               
                 urine for culture sensitivity. Started Zeniquin at 12.5 mg/day dissolved in Rebound electrolyte solution. Reglan was 
               
               
                 given for nausea. 
               
               
                 When seen on Nov. 24, 2004, was presented on a blanket in lateral recumbancy. Had urinated blood tinged urine 
               
               
                 on bedding. Lab reported isolating  E. coli , sensitivity pending. Other abnormal values: BUN (55 mg/dl), Phos (10.6 
               
               
                 mg/dl), Sodium (162 mEq/L), Osm (340 mOs/L and WBC elevated at 19,100. Since Pinga had gotten progressively 
               
               
                 worse over the course of antibiotic therapy, and now appeared to be approaching endotoxic shock Tamiflu was 
               
               
                 begun at 2 PM.  E. coli  is a neuraminidase dependent bacteria. 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Physical Exam: 
                 Temp:  
                 99.9 F. 
                 Pulse:  
                 140/min 
                 Weight:  
                 8.06 lbs. 
               
               
                   
                 Resp: 
                   
                 % Dehy:  
                 Slight 
                 Parvo Test:  
                 Not Done 
               
            
           
           
               
               
            
               
                   
                 Pinga was presented laying on her side unable to sit or stand. 
               
               
                   
                 She had a decreased capillary refilling time and temperature was subnormal. 
               
            
           
           
               
            
               
                 Tamiflu dose: 1 mg/lb . . . that dose given every 12 hours for a total of 10 treatments 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Treatment 
                 Drugs/Fluids 
                 Observations 
               
               
                   
               
               
                 1st. 
                 Dissolved 12.5 mg Zeiniquin in 12 cc of 
                 Can not sit or stand, urinated in bed this 
               
               
                 Date: 
                 Rebound and gave PO 
                 morning . . . urine was blood tinged. E.coli 
               
               
                 Nov. 24, 2004 
                 Gave 12 mg Tamiflu (1 cc)/PO at 2:00 PM 
                 cultured . . . sensitivity pending. 
               
               
                 Temp: 
                   
                   
               
               
                 99.8 F. 
                   
                   
               
               
                 2nd. 
                 Gave 12 mg Tamiflu (1 cc) at 5:35 PM 
                 Pinga is more alert and has not vomited 
               
               
                 Date: 
                   
                 since receiving Tamiflu. Can not stand, 
               
               
                 Nov. 24, 2004 
                   
                 but can sit upright. 
               
               
                 3rd. 
                 Dissolved 12.5 mg Zeniquin in 12 cc of 
                 No vomiting since starting Tamiflu..is 
               
               
                 Date: 
                 Rebound and gave PO 
                 drinking water . . . walked 20 feet and urinated 
               
               
                 Nov. 25,2004 
                 Gave 12 mg Tamiflu/PO at 10:15 AM 
                 a clear yellow colored urine next to litter box. 
               
               
                 Temp: 
                   
                 About 1:30 AM, left bed, walked to owner&#39;s 
               
               
                 99.5 F. 
                   
                 bed, jumped up and began to purr 
               
               
                 4th. 
                 Tamiflu and Parvo Clinical Trial 
                 Urinated, was normal yellow color . . . has 
               
               
                 Date: 
                 Gave 12 mg Tamiflu/PO at 5:30 PM 
                 begun to walk around house . . . jumped 
               
               
                 Nov. 25, 2004 
                   
                 and ran when attempted to brush . . . Pinga 
               
               
                 Temp: 
                   
                 is more alert in clinic 
               
               
                 98.9 F. 
                   
                   
               
               
                 5th. 
                 Dissolved 12.5 mg Zeniquin in 15 cc 
                 Pinga is walking around house . . . slept in 
               
               
                 Date: 
                 Rebound and gave PO at 10:30 AM 
                 owner&#39;s bed..refused being given Rebound 
               
               
                 Nov. 26, 2004 
                 Gave 12 mg Tamiflu/PO 
                 by syringe . . . comes when called . . . Physical 
               
               
                 Temp: 
                   
                 exam is normal 
               
               
                 98.8 F. 
                   
                   
               
               
                 6th. 
                 Gave 12 mg Tamiflu/PO at 5 PM 
                 Urinated normal urine . . . passed 3 small 
               
               
                 Date: 
                   
                 firm BMs . . . jumped up to help iron clothes, 
               
               
                 Nov. 26, 2004 
                   
                 vocal . . . First time temperature has been 
               
               
                 Temp: 
                   
                 above 100 F. 
               
               
                 100.6 F. 
                   
                   
               
               
                 7th. 
                 Dissolved 12.5 mg Zeniquin in 15 cc 
                 Beginning 3rd day of Tamiflu . . . Pinga is 
               
               
                 Date: 
                 Rebound 
                 more alert . . . began to eat Wellness dry 
               
               
                 Nov. 27, 2004 
                 Gave 12 mg Tamiflu/PO at 10:30 AM 
                 cat food . . . had BM in litter box . . . continues 
               
               
                 Temp: 
                   
                 to be given Rebound via syringe at home 
               
               
                 98.8 F. 
                   
                   
               
               
                 8th. 
                 Gave 12 mg Tamiflu/PO at 5 PM 
                 Appears to be “normal”, alert, active and 
               
               
                 Date: 
                   
                 interested in surroundings . . . Dispensed 
               
               
                 Nov. 27, 2004 
                   
                 CNM-EN as a semi-soft food to try at home 
               
               
                 Temp: 
                   
                   
               
               
                 Not Taken 
                   
                   
               
               
                 9th. 
                 Dissolved 12.5 mg Zeniquin in 15 cc 
                 Ate CMN-EN last night, urinated normally, 
               
               
                 Date: 
                 Rebound 
                 almost “normal” . . . maybe weak in rear 
               
               
                 Nov. 28, 2004 
                 Gave 12 mg Tamiflu/PO at 10:30 AM 
                 when playing with ball . . . shows interest 
               
               
                 Temp: 
                   
                 when Jerry is tying shoe strings . . . this is 
               
               
                 100.1 F. 
                   
                 a normal activity for Pinga 
               
               
                 10th. 
                 Gave 12 mg Tamiflu/PO at 5:30 PM 
                 Pinga appears to be normal . . . this is his 
               
               
                 Date: 
                   
                 last treatment with Tamiflu. 
               
               
                 Temp: 
                   
                   
               
               
                 Not Taken 
               
               
                   
               
            
           
         
       
     
     In Table 16,  E. coli , a neuraminidase dependent bacteria, was cultured from Pinga&#39;s urine followingan acute onset of vomiting and hematuria. She failed to respond to Zeniquin, but had a dramatic reversal when TAMIFLU was started on Nov. 24, 2005 when she presented in an endotoxic condition. This case demonstrates the success of TAMIFLU in cases of  E. coli  enterotoxemia. 
     Oral Nasal  Candida famata  in an Adult Male Cat 
     An adult neutered male domestic shorthair white cat was seen at the Cat Health Clinic for a second opinion. During the past 2 weeks, the cat had been seen and treated by three other veterinary clinics and one emergency veterinary clinic for an upper respiratory infection. Typically, most feline upper respiratory infections are caused by a combination of a virus and one or more bacteria. The lesions seen in these infections are usually ulcerative and painful. This cat&#39;s presentation was different in that there were no ulcers with the primary complaint was the excessive mucous being produced resulting in a reduced ability to get air into the lungs. This excessive mucous also prevent any intake of food, leading to weight loss poor tissue oxygenation. This mucous was very viscous and tenacious leading the cat to collapse from lack of oxygen and had been kept in an oxygen cage prior to entry. Each veterinarian had placed an esophageal-gastric feeding tube only to have it fall out due to the slickness of the mucous. 
     Physical examination found the cat to be emaciated (5.1 lbs) who was anemic (PCV 20%), elevated liver enzymes and total bilirubin. Both FeLV/FIV tests were negative and stress induced hypothyroidism. In-house cytology mixed rod and cocci bacteria and degenerate neutrophils in the oral cavity. The most significant finding was the presence of long non-septed pseudohyphae and blastospores typical of  Candida  spp in samples taken from the nares, oral cavity and anterior esophagus. (photo of blastospores). There had been no response to either Doxycycline or Zithromax given during the previous 2 weeks. Typically, it is known to those skilled in the art that the use of antibiotics can have enhanced the growth of the yeast. 
     A tentative diagnosis of  Candida  spp. Infection was offered. Since  Candida  spp use neuraminidase as a virulence factor, oseltamivir phosphate was started at 2 mg/lb given every 12 hours. Oral Zeniquin/Molasses suspension was started to treat the mixed bacterial flora present on the cytology slides. Daily nebulization to reduce the viscosity of the exudate and Marinol was given to stimulate his appetite. 
     There was a dramatic decrease in the production of the oral-nasal discharge 12 hours after therapy was initiated. The patient began to eat canned cat food after 12 hrs of treatment. Within 48 hrs of treatment, the patient began to clean himself. 
     Itraconazole was continued for 3 weeks and the Zeniquin/Molasses was stopped after 14 days. The oseltamivir phosphate was given for 3 weeks even though the clinical signs had been resolved after 72 hours of treatment. 
     This case is an example of using the Theory of Biological Intervention in a clinical yeast/fungal infection. The Theory of Biological Intervention states that one can treat most infections by suppressing one of more of the pathogen&#39;s virulence factors. In this case, neuraminidase is a virulence factor of  Candida famata.    
       Tritrichomonas Foetus  in a Cat Treated with Oseltamivir Phosphate 
     History: Calorie was a six-year-old red tabby neutered domestic shorthair cat when he was first presented to a veterinarian for diarrhea. Both direct and flotation exams for fecal parasites were negative and he was dismissed with the gastrointestinal antibiotic Flagyl. Five weeks later, Calorie was seen by a second veterinarian where he underwent endoscopy. These studies failed to find any pathology and he was dismissed with a special GI diet and an oral antibiotic. A fecal sample was submitted to the North Carolina State College Of Veterinary Medicine (NCSCVM) to be tested for  Tritrichomonas foetus.    
     Two days later, Calorie was seen at the Cat Health Clinic for a second opinion. A tentative diagnosis of Inflammatory Bowel Disease was offered. Treatment consisted of a SQ injection of 4 mg Azium/5 mg Vetalog, a SQ inj of Vitamin B-12 and home with oral Zithromax to treat possible  Bartonella  spp. Calorie returned six days later with bloody diarrhea, and a positive test for  Tritrichomonas foetus  from NCSCVM. 
     Trichomonads are spindle to pear-shaped, highly motile protozoan that divide by binary fission and are transmitted directly via the fecal-oral route. Cats that are infected with  T. foetus  are generally young and presented for a waxing and waning large bowel diarrhea that contains fresh blood and mucus. The diarrhea is semi formed and malodorous. 
     Cats infected with  T. foetus  have failed when treated with numerous antimicrobial drugs. Despite this failure to eradicate  T. foetus , the stools always improve while taking antibiotics, only to relapse once the drug is discontinued. Cats that have failed antibiotic treatments do tend to improve after a period of infection lasting over two years. Ronidazole, a nitroimidazole, has been shown to be effective in curing cats with  T. foetus  infections. Unfortunately, ronidazole can be potentially carcinogenic and humans should avoid exposure to this drug. In cats given ronidazole have developed ataxia, nystagmus and behavior changes. These signs of neurotoxicity are reversible when ronidazole is discontinued. Given the choice of their cat developing signs of neurotoxicity and a good chance of a spontaneous resolution of  T. foetus  in two years, most clients choose not to treat with ronidazole. 
     Oseltamivir phosphate was given at the dose of 2 mg/lb every 12 hours for a total of 10 treatments. Photographs were taken of every stool during the treatment. The stool went from a bloody gravy (Bristol 6) to a non-bloody formed stool (Bristol 4) after the 5th treatment. The treatments were completed and there has been no relapse in over four years. 
     Calorie is a typical case of feline  T. foetus  with relapsing bloody diarrhea over a period of six months. Once the diagnosis of  T. foetus  was made, the decision was made to not try and kill the  T. foetus  organism with ronidazole, but to intervene biologically by suppressing  T. foetus &#39; ability to secrete neuraminidase and thus prevent it from harvesting neuramic molecules from the host. By suppressing one of  T. foetus &#39; virulence factors, we were able to stop the infection. Suppressing  T. foetus &#39; ability to secrete neuraminidase proved to be a safe economical treatment for a clinical disease. 
     Resistant Bacteria 
     In yet another example illustrating the use of oseltamivir phosphate to treat a bacterial infections resistant to antibiotics, such as  Enterococcus faccalis , in which the pathogen is a neuraminidase producer, specifically where the most of the potential drugs were ineffective (bacteria was resistant). In addition, bacterial sinusitis infections in the frontal sinuses can be almost impossible to treat. 
     The pathogen was a gram (+) rod bacteria that produces neuraminidase as a virulence factor. By using a neuraminidase inhibitor, for example, oseltamivir phosphate to suppress bacterial salidase, we were able to totally resolve this problem by administering 1 mg/ml, q. 12 h of oseltamivir phosphate for ten consecutive treatments. 
     A shelter cat with a bulging area in the area of the frontal sinuses due to pus from a very resistant bacteria. Frontal sinus infections typically can be extremely difficult to treat due to the location (a cavity in the skull surrounded by bone). Most of these cases require surgical removal of the nasal bone followed inserting tubes that allow the area to be flushed daily for weeks usually with little progress. 
     Oseltamivir phosphate was given to the cat, in addition to an antibiotic, that changed the course of the disease. 
     Necrotic Enteritis ( Clostridium perfringens ) in Poultry Treated with  Tamerindus indicus  and  Combretum fragrans    
     Materials and Methods 
     A. Experimental Ration An unmedicated commercial type chicken started compounded with feedstuffs commonly used in the United States was formulated. This ration (in mash forms) was fed ad libitum from the date of chick arrival until Day 28 of the study. The diet formulation was included in the source data. Experimental treatment feeds were prepare from this basal starter feed. Quantities of all basal feed and test articles used to prepare treatment batches were documented. Treatment feeds were mixed at SPR to assure a uniform distribution of respective test article. The feed was transferred to Building #2 and distributed among cages of the same treatment.
 
Feed samples: One each from the beginning, middle and end of each batch of treatment diet were collected an mixed to form a composite sample. One composite sample was taken from the composite for each treatment and sent to Jack J. Broadhurst, DVM.
 
B. Animals: On Jul. 18, 2013, day of hatch male broiler chicks were obtained from Cobb-Vantress, Cleveland, Ga. The strain was Cobb X Cobb 500. Breeder flock information was recorded. At the hatchery, the birds were sexed and received routine vaccinations. Only healthy appearing chicks were used in the study. Number and disposition of all birds not used for allocation were documented.
 
C. Housing: Upon arrival, chicks were raised in Petersime battery cages. At placement the birds were fed the treatment feeds. The Petersime batteries were located in Building #2 at SPR, an insulated, concrete floored, metal structure that measures 40 ft by 100 ft in a north-south direction. The floor space per animal was 0.63 sq.ft/bird. The feeder space per bird was 8 birds/24×3.5 inch feeder. Thermostatically controlled gas furnace/air conditioner maintained uniform temperature. Even illumination was provided.
 
     Procedures 
     A. Bird Allocation and Cage Randomization: Assignment of treatments to cages was performed by SPR. Cages were blocked by location in the battery with block size equal to treatments (6 cages per block). The study began when the birds were placed (day of hatch) (DOT 0) at which time they were allocated to the experimental cages. Only healthy birds were selected. On DOT 0, group body weights were recorded by cage. No birds were replaced during the course of stay.
 
B. Disease Induction: Feed and water were available ad libitum throughout the trial. On DOT 14, all birds were orally inoculated with coccidial inoculum containing approximately 5,000 oocysts of  E. maxima  per bird. Coccidial oocyst inoculation procedures are described in SPR SOP. Starting on DOT 19, all birds, except Treatment 1, were given a broth culture of  C. perfringens  10 8  cfu/ml. The birds were administered a fresh broth culture once daily for 3 days (on DOTs 19, 20 and 21).
 
C. DOT 0, 14, 21 and 28 Weights: All birds weighed by cage on DOT 0, 14, 21 and 28. Feed was weighed in on DOT 0 and remaining feed was weighed on DOT 14, 21 and 28. The trial was terminated on DOT 28.
 
D. Necrotic Enteritis Intestinal Lesion Scoring: On DOT 21, three birds from each cage were selected, sacrificed, weighed and examined for the degree of presence of Necrotic Enteritis lesion. The scoring was based on a 0 to 3 score, with 0 being normal and 3 being the most sever.
 
     E. Management: 
     1. The facility was checked thoroughly to assure that all cages had water and that feed was available in every cage. The building temperature&#39;s range was maintained at an appropriate temperature for the age of the birds. 
     2. Even, continuous illumination was provided by fluorescent lamps hung vertically along the wall. 
     3. Feed and water were given ad libitum. 
     4. In accordance with SPR&#39;s standard operating procedures (SOPs), the cages were checked twice daily. Observations included were the availability of feed and water, temperature control, and any unusual conditions. The birds were watched closely for any abnormal reactions. 
     5. When mortality birds were removed from cages, the cage number, date, weight of the bird, sex and probably cause of death were recorded. 
     DATA ANALYSIS: Means for cage, weight gain, feed consumption, feed conversion, lesion scores, and mortality were calculated.
 
DISPOSAL of ANIMALS and Feed: All birds were buried in SPR&#39;s pit as described in SPR SOPs. Records of disposition were included in the source data.
 
     
       
         
           
               
             
               
                 TABLE 17 
               
               
                   
               
               
                 Comparative Efficacy of a 50/50 combination of  Tamerindus indicus  and  Combretum   
               
               
                   fragrans  to AGP administered in the feed for the Control of Necrotic Enteritis caused by 
               
               
                   Clostridium perfringens  in Broiler Chickens 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Feed Consumption 
                 Feed Conversion 
                 Weight Gain 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Treatment 
                 Day 0-21 
                 Day 14-21 
                 Day 0-21 
                 Day 14-21 
                 Day 0-21 
                 Day 14-21 
               
               
                   
               
               
                 1) Nonmed, Noninfect 
                 6.694 bc 
                 3.187 c 
                 1.764 d 
                 1.827 c 
                 0.482 a 
                 0.226 a 
               
               
                 2) Nonmed, Infected 
                 7.080 ab 
                 3.513 ab 
                 2.157 a 
                 2.713 a 
                 0.418 b 
                 0.174 d 
               
               
                 3) Virginamyein 20 g/t 
                 7.151 a 
                 3.468 a 
                 1.894 c 
                 2.141 b 
                 0.480 a 
                 0.213 ab 
               
               
                 4) Tamerindus (0.25%) &amp;  
                 6.915 abc 
                 3.342 abc 
                 2.044 ab 
                 2.381 b 
                 0.435 b 
                 0.188 bcd 
               
               
                 Combretum (0.25%) 
                   
                   
                   
                   
                   
                   
               
               
                 5) Tamerindus (0.50%) &amp;  
                 6.479 c 
                 3.153 c 
                 2.020 bc 
                 2.191 b 
                 0.404 b 
                 0.183 cd 
               
               
                 Combretum (0.50%) 
                   
                   
                   
                   
                   
                   
               
               
                 6) Tamerindus (1.0%) &amp; 
                 6.740 bc 
                 3.279 bc 
                 1.998 bc 
                 2.129 ab 
                 0.432 b 
                 0.203 abc 
               
               
                 Combretum (1.0%) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Feed Consumption 
                 Feed Conversion 
                 Weight Gain 
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Treatment 
                 Day 0-28 
                 Day 14-28 
                 Day 0-28 
                 Day 14-28 
                 Day 0-28 
                 Day 14-28 
               
               
                   
               
               
                 1) Nonmed, Noninfect 
                 8.915 ab 
                 5.408 a 
                 1.818 c 
                 1.902 b 
                 0.746 a 
                 0.490 a 
               
               
                 2) Nonmed, Infected 
                 8.802 ab 
                 5.235 a 
                 2.140 a 
                 2.458 a 
                 0.651 c 
                 0.406 c 
               
               
                 3) Virginamyein 20 g/t 
                 9.406 a 
                 5.723 a 
                 1.878 bc 
                 1.999 b 
                 0.747 a 
                 0.480 ab 
               
               
                 4) Tamerindus (0.25%) &amp;  
                 8.543 ab 
                 4.970 a 
                 1.913 bc 
                 2.016 b 
                 0.702 ab 
                 0.454 ab 
               
               
                 Combretum (0.25%) 
                   
                   
                   
                   
                   
                   
               
               
                 5) Tamerindus (0.50%) &amp;  
                 8.295 b 
                 4.969 a 
                 1.954 b 
                 2.015 b 
                 0.630 c 
                 0.409 c 
               
               
                 Combretum (0.50%) 
                   
                   
                   
                   
                   
                   
               
               
                 6) Tamerindus (1.0%) &amp; 
                 8.467 b 
                 5.006 a 
                 1.887 bc 
                 1.882 b 
                 0.672 bc 
                 0.444 bc 
               
               
                 Combretum (1.0%) 
               
               
                   
               
            
           
           
               
               
               
            
               
                   
                 NE (0-3) 
                 % NE 
               
               
                 Treatment 
                 Lesion Score 
                 Mortality 
               
               
                   
               
               
                 1) Nonmed, Noninfect 
                 0.0 b 
                  0.0 b 
               
               
                 2) Nonmed, Infected 
                 0.4 a 
                 14.1 a 
               
               
                 3) Virginamvein 20 g/t 
                 0.2 ab 
                  0.0 b 
               
               
                 4) Tamerindus (0.25%) &amp; Combretum (0.25%) 
                 0.3 ab 
                 10.9 a 
               
               
                 5) Tamerindus (0.50%) &amp; Combretum (0.50%) 
                 0.3 ab 
                  4.7 ab 
               
               
                 6) Tamerindus (1.0%) &amp; Combretum (1.0%) 
                 0.1 ab 
                  1.6 b 
               
               
                   
               
            
           
         
       
     
     Anaerobic Antibiotic Resistant Nosocomial Infection 
     History: On Aug. 20, 2013, a forty-three years old Caucasian male living in Lyon, France underwent an arthroscopic procedure on his right knee. The patient was instructed to begin Paracetamol to control pain associated with the surgery. Paracetamol is a French OTC product that contains acetaminophen). 
     He returned on Sep. 13, 2013 complaining that his right knee was swollen and painful. An aerobic bacterial culture was submitted on the synovial fluid that was removed during an arthroscopic procedure that also removed an osseous spur.  Staphylococcus lugdunensis  was isolated from the sample submitted.  Staphylococcus lugdunensis  is an aerobic Gram positive cocci frequently associated with orthopedic surgery and is susceptible to multiple antibiotics. On Sep. 20, 2013, the patient was started on two oral antibiotics known to effective against  Staphylococcus lugdunesis : Pyostacine (500 mg) and Oflocet (200 mg). Pyostacine (Pristinamycin) is effective against  Staphylococcus  and  Streptococcus  infections. Oflocet (Ofloxacine) is effective against  Staphylococcus, Streptococcus, Proteus, Neisseria, Chlamydia, Escherichia, Klebsiella, Pseudomonas  and  Citrobacteria  infections. 
     On Oct. 1, 2013, a third arthroscopic procedure was done and synovial fluid removed and submitted for culture. This second aerobic culture was reported out as “No Growth”. There had been no change in the degree of pain and swelling while taking Pyostacine and Oflocet. The patient was told to remain sedentary and continue to use a crutch if he needed to move around his apartment. Paracetamol was replaced with oral Bi-Profenid (ketoprofene, an NSAID used for pain secondary to osteoarthritis). 
     A recheck on Oct. 13, 2013 found that there had been no change in the degree of pain and swelling. The patient was ordered to stop Pyostacine and Oflocet. Arrangements were made for a nurse to come to the patient&#39;s apartment once a day and to administer 2 gm of Rocephine once a day by a slow drip of IV fluids. This treatment began on Oct. 18, 2013 and ended on Oct. 30, 2013. 
     Rocephine (Cetriaxone) has proven to be effective against: Gram negative bacteria:  Acinetobacter, Enterobacter, Escherichia, Klebsilella, Moraxella, Neisseria, Proteus, Pseudomonas  and  Serratia  spp. 
     Gram positive bacteria:  Staphylococcus  and  Streptococcus  spp.
 
Anaerobic bacteria:  Bacteroides, Clostridium  and  Peptostreptococcus  spp.
 
     No antibiotics were given after the last Rocephine infusion on Oct. 30, 2013. In an attempt to better control the patient&#39;s pain, Bi-Profenid was replaced with Lamoline (combination of acetaminophen+opiate+caffeine) and Tramadol which is a mild narcotic used for moderate to sever pain. 
     On Nov. 17, 2013, a recheck examination found that there had been no change in the degree of pain and swelling. A third aerobic culture was submitted using synovial fluid removed from the knee joint. This was reported out as a “No Growth”. The patient was ordered to continue to take Lamoline and Tramadol to control pain and to limit activity to his apartment and use crutches when required to walk. The doctors discussed amputation as the last resort to remove the source of pain and swelling. 
     On Nov. 26, 2013, the patient contacted Dr. Jack Broadhurst and asked if there were any alternatives to amputation. After reviewing his medical history, Dr. Broadhurst suggested that the French doctors had not ruled out an anaerobic, antibiotic resistant nosocomial (hospital source) infection. 
     In the United States,  Enterococcus faecalis  is one of the leading causes of nosocomial infection and in many cases has been reported to resistant to all available antibiotics. Dr. Broadhurst has had success treating  E. faecalis  with a neuraminidase inhibitor (Oseltamivir Phosphate). He suggested that the patient locate a source of Oseltamivir Phosphate and start taking 1 mg/lb (0.5 mg/kg) every 12 hours. If there was no change in the degree of swelling or pain, after two doses, the patient should increase the dose for the remaining doses to 2 mg/lb (1 mg/kg). 
     On Nov. 29, 2013, the patient obtained Oseltamivir Phosphate and began taking 150 mg every 12 hours. 
     
       
         
           
               
               
               
             
               
                   
               
               
                 Date 
                 AM/PM 
                 Clinical Response 
               
               
                   
               
             
            
               
                 Nov. 29, 2013 
                 PM 
                 Initial dose of 150 mg (PO) 
               
               
                 Nov. 30, 2013 
                 AM/PM 
                 All pain gone, swelling 
               
               
                   
                   
                 reduced 30% 
               
               
                 Dec. 1, 2013 
                 AM/PM 
                 Got out of bed, able to stand 
               
               
                   
                   
                 without crutches, walked 
               
               
                 Dec. 2, 2013 
                 AM/PM 
                 Walked down stairs, walk 
               
               
                   
                   
                 to local park, kicked soccer 
               
               
                   
                   
                 ball 
               
               
                 Dec. 3, 2013 
                 AM/PM 
                 Biked to park, normal gait 
               
               
                   
                   
                 played goalie in soccer 
               
               
                   
                   
                 game 
               
               
                 Dec. 4-5, 2013 
                 AM/PM 
                 Normal gait and activity 
               
               
                 Dec. 6-13, 2013 
                 AM 
                 Reduced to 150 mg per day 
               
               
                 Dec. 14, 2013-Current Date 
                   
                 No relapse 
               
               
                   
               
            
           
         
       
     
     The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds and the particular embodiments. Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention. Thus, the true scope of the present invention is not limited to any one of the foregoing exemplary embodiments.