Lanoxin

Sarah M. Creighton, MD, FRCOS

Consultant Gynaecologist,
University College Hospital,
London, United Kingdom

The inoculum size and the biology of the pathogen arteria carotis interna order lanoxin 0.25 mg mastercard, of progression to persistent diarrhea (Moore and others in particular pulse pressure nursing purchase cheap lanoxin on-line, its virulence attributes 2010) heart attack young man buy 0.25 mg lanoxin mastercard. The susceptibility of the host arrhythmia cardiac discount 0.25 mg lanoxin free shipping, including previous diarrhea accounted for only 11 heart attack people discount 0.25mg lanoxin with mastercard. The health and nutritional status of the individual at acute to prolonged diarrhea increased the overall risk of the time of exposure heart attack left or right order 0.25mg lanoxin mastercard. As a result, natural history following infection can Once diarrhea is persistent, mortality rates increase vary from no symptoms, to mild moderate self limited sharply (Grimwood and Forbes 2009), in some settings illness, to severe life threatening disease. Individuals who accounting for as much as 50 percent of overall diar are healthier and better nourished at exposure are less rhea mortality. Continuing reductions in acute diarrhea likely to develop severe illness after a given inoculum of deaths has increased attention to mortality associated a specific pathogen. Early and appropriate management with persistent diarrhea, which is relatively heightened of clinical manifestations improves outcomes and can be as a consequence. A few pathogens have been particularly associated with persistence or are preferentially identified when Watery Diarrhea an episode becomes persistent, including a subgroup of Watery diarrhea is classified according to stool volume: diarrhea causing E. Serial exposure to these 166 Reproductive, Maternal, Newborn, and Child Health or other pathogens may also be involved. As the duration in Peruvian infants are also associated with slower of illness extends, malnutrition becomes increasingly weight gain compared with uninfected infants, albeit to prominent because of ongoing mucosal injury, anorexia, a lesser extent than infants with symptomatic infections malabsorption, and nutrient losses (Newman and others (Checkley and others 1997). Shigella infection, characterized by intense tis tomatic infections were twice as common as diarrhea, sue catabolism and nutrient losses, almost doubles the their ultimate effects might exceed those of clinical diar risk of persistent diarrhea (Ahmed and others 2001). Moreover, infants infected with Cryptosporidium As the frequency of Shigella infection dropped from during the first six months of life remained stunted at age 1991 to 2010 in Bangladesh, the frequency of persistent one year, despite some interval catch up growth (Bushen diarrhea diminished as well (Das and others 2012). Early coloni Mucosal injury also explains why the manifestations of zation with H. Limited biopsies from infants and young children cal and structural alterations of the gut with adverse con revealed normal, slender finger like villi at birth, but sequences on child nutrition and growth. For example, a jejunum of older infants and children resembled the handwashing intervention not only reduced the number adult gut, suggesting these changes were acquired after of diarrhea episodes by 31 percent (4. This constellation of findings was called tive of abnormal mucosal permeability had significantly tropical or subclinical enteropathy/jejunitis/malabsorp lower height for age z scores (p= 0. However, Although the malabsorption may be limited, chronicity the significance of enteropathy remained unclear, and may be sufficient to produce overt malnutrition over interest waned because no relationship to pathogenesis time, especially when dietary nutrient intake is marginal. Subclinical infections with intestinal pathogens have In retrospect, the extent of the weight loss associated been shown to underlie growth faltering (Guerrant and with enteropathy in adults was dismissed too quickly; others 1999). Giardia intestinalis, which causes diarrhea the same decrement occurring in young infants would associated with growth retardation in infants (Newman raise concerns about incipient malnutrition. Recently, and others 2001), is often identified in the stools of investigators in Sub Saharan Africa, using newer assess asymptomatic children in endemic areas, and a cor ments of intestinal permeability, identified alterations in relation between asymptomatic Giardia infection and young infants associated with altered gut histology and growth faltering has been reported (Prado and others poor growth in early childhood (Campbell, Lunn, and 2005). Asymptomatic first Cryptosporidium infections Elia 2002; Campbell and others 2004). Inflammatory Diarrheal Diseases 167 cells present in the intestinal mucosa were identified as or immune activation have been identified (Kosek immunoreactive T cells (Veitch and others 1991), linked and others 2013). A composite activity score of three to strong pro inflammatory local cytokine responses stool biomarkers of intestinal inflammation (neopterin, (Campbell and others 2003). These findings have rekin alpha1 antitrypsin, and myeloperoxidase) during peri dled interest in their physiological significance, anal ods without diarrhea is inversely correlated with linear ogous to inflammatory bowel disease. If changes in intestinal structure and function sodes restrict the capacity for catch up growth (Salomon, develop in young infants in impoverished communities Mata, and Gordon 1968). The effects of diarrheal diseases early in life, presumably due to environmental exposure can be both short term and long term. In the short term, to still unknown inciting factors, the consequence may patients experience adverse systemic impacts on appetite, be initial malabsorption leading to early malnutrition, metabolism, and nutrition due to the infection. In the growth faltering, and increased susceptibility to diarrheal longer term, mucosal changes can alter digestion, absorp disease (Keusch and others 2013). Some interven Vaccines tions, such as nutritional support and zinc supplemen Improved nutrition: tation, can be beneficial for both purposes. Interventions vitamin A, zinc can also be classified by scale: individuals, households, or communities. Some depend on infrastructure; others are behavioral, determined by understanding and compli ance at the level of the household, community, or health contradictory, of poor reliability, or difficult to interpret. Although most interventions are not new, Similarly, the use of drugs to restore physiological func innovations to make them more accessible or effective tions of the intestine is not considered because of limited can have adverse unintended consequences, such as reliable data in target human populations. In the Democratic Republic of Congo, ondansetron, is limited because safety and efficacy data more practitioners relied on pharmaceutical companies in poorly nourished children under age five years are for prescribing recommendations (73. Parental expectations of treatment reporting leftover antibiotics at home said they would are also influenced by previous experience. Experts agree that anti Limited information precludes rigorous assessment of biotics are usually unnecessary for acute watery diar the impact of community case management on mortal rhea; most episodes are mild and self limited, and many ity, but trends suggest a decrease of 63 percent among are due to viruses, especially among young children children ages 0?4 years (95 percent confidence interval (Kotloff and others 2013). It is time to abandon rou 7?85 percent) and 92 percent (95 percent confidence tine use of antibiotics to shorten duration of illness in interval 13?100 percent) among children age 0?1 year. Overuse is fostered by multiple causes: caregiver tially transferable to other enteric pathogens as well expectations; lack of knowledge; prescriber behavior; (Kruse and others 1995). The emergence of resistance lack of etiology specific point of care diagnostics; fail in V. Routine use of when prescriptions are required (Adriaenssens and oth quinolone may be appropriate in certain circumstances. Improved practitioner and parent knowledge these include treatment of the most severely purging 170 Reproductive, Maternal, Newborn, and Child Health cases (Harris and others 2012), during epidemics that Preventive Interventions overwhelm clinical capacity (Ernst and others 2011), or Preventive measures to reduce exposure to enteric patho when elimination of viable V. Morbidity and mortality Vaccines to improve immunity are presently limited due to inflammatory diarrheas, most often caused by to rotavirus, the only vaccine approved and increas Shigella invading the intestinal mucosa, are not caused ingly available to prevent moderate to severe rotavirus by dehydration but rather by tissue damage. Improving health and immune function by bers of leukocytes are recruited to the invasion site, lead improving nutritional status is another effective measure. These metabolic responses persist Vaccines for weeks after acute infection, and drive continuing For public health, prevention is always preferable to malnutrition (Raqib and others 1995), a major reason treatment, but effective treatment is necessary when why post shigellosis mortality remains high for months prevention fails. The ics are indicated include grossly bloody stools or dysen complexity for diarrheal disease is that vaccines are tery, usually with accompanying fever. Most episodes are pathogen specific and often serotype or serogroup bacterial in etiology, and Shigella or sometimes related specific. Unfortunately, vaccines for diarrheal diarrhea is bacterial in origin and antibiotics appro diseases have met with developmental challenges, in priate for shigellosis should be initiated. This regimen part because the basis of effective immunity is poorly will likely be adequate for other possible bacterial eti understood, and because diarrheal disease is most ologies. Two vaccines produced by Merck and tial to guide therapeutic decisions (O?Ryan, Prado, GlaxoSmithKline are widely used in high income and Pickering 2005). Ciprofloxacin, azithromycin, rus vaccines have been licensed in China or Vietnam for or pivmecillinam, where available, are reasonable initial local use only. The well beyond the known timing of vaccine related intus challenge is to increase adherence to current principles susception, and so were unlikely to be vaccine related. In the first two years, 604,634 cases?with 329,697 hospitalizations and 7,436 deaths?were reported. However, analyses concluded it should not be Gavi, the Vaccine Alliance has added rotavirus to deployed because of serious obstacles, including lim its support program, and 19 of the 35 Gavi eligible ited vaccine availability, complex logistics, operational countries now include rotavirus vaccine in their rou challenges of a multidose regimen, and population tine immunization programs; this number is expected displacement and potential civil unrest (Kashmira and to increase to 30 during 2015 (Gavi Alliance 2014). Universal implementation of rotavirus vaccine talized patients (Steenland and others 2013). A subse could prevent many episodes of severe diarrhea (Fischer quent vaccine demonstration trial in Haiti showed that Walker and Black 2011) and reduce the number of high coverage with two doses of vaccine was, in fact, diarrhea deaths under age five years by 70,000?85,000 feasible (Rouzier and others 2013). This paved the way per year, and reduce hospitalizations and associated for an ambitious immunization program, justified by costs by an average of 94 percent (Munos, Fischer the dreadful state of water and sanitation facilities in Walker, and Black 2010). The potential of vaccines to mitigate the sion for rotavirus diarrhea in India may be as much as extent of epidemic cholera and improve the impact 5. The global burden of morbidity and mortality and Clemens 2010); this plan is being implemented of cholera is high; an estimated 2. Incidence is highest in children under age five years, who may account for as much as 50 percent Other pathogens. It is notable that 67 percent of inpa remain under research and development; no licensed tient cholera deaths in Bangladesh were actually associ products are available, particularly for agents highly ated with pneumonia rather than dehydration (Ryan and associated with moderate to severe diarrhea, including others 2000), increasing to 80 percent in children under enterotoxigenic E. Identification and appropriate treatment of More recently, norovirus has been identified as a poten these patients will reduce mortality. Modeling based on clinical trials in disease (Feachem and Koblinsky 1983), presumably Bangladesh suggests a herd immunity effect with as high because measles is immunosuppressive and exacer as a 93 percent reduction in incidence if only 50 percent bates malnutrition. The current campaign for measles of the population is immunized (Longini and others elimination through universal immunization not only 2007). Reduced incidence would also reduce the use of addresses measles, but has additional beneficial effects antibiotics (Okeke 2009). Malnutrition is a consequence of and a risk ferentiation, and immune function, and promotes factor for diarrheal disease (Mondal and others 2012). Dietary management of acute diarrhea with hospital admissions (Fischer Walker and Black 2010). A pooled analysis of the effect reduced susceptibility to diarrheal disease and other of supplementary oral zinc in children under age five infections (Bhutta and others 2013; Dey and others years with persistent diarrhea reduced the probability 2013; Strand and others 2012). Strand and others (2012) conclude that breast development of children, with or without diarrhea. Bottlenecks billion in 2005 dollars through 2014 for water and san include limited knowledge among care providers itation, respectively, exclusive of programmatic costs and parents, price, and availability. Scaling up use of beyond the intervention delivery point (Hutton and zinc, including promotion and distribution through Bartram 2008). Once built, however, water and sanitation infrastructure need to be maintained; this ongoing requirement leads to Water, Sanitation, and Hygiene substantial additional financial as well as human capacity Because diarrhea is ultimately transmitted from infected investments, without which infrastructure deteriorates stools, clean water and safe disposal of feces have major and the initial investment can be lost. If improved practices document greater effectiveness of combinations over became the norm, risk of diarrhea and morbidity and single interventions (Fewtrell and others 2005). Each of these behaviors assessments are not sufficiently robust to influence may be difficult to sustain, but each would have a major investment decisions in one strategy over another, impact. Handwashing As infrastructure projects, water and sanitation the transfer of infectious agents via the hands directly improvements can be built at the community, neighbor between individuals or indirectly through contamination hood, or individual household levels; may be more or less of inanimate objects (fomites), such as dishes, utensils, and technically complex; and may be more or less expensive. Contaminated hands seafood sources may become contaminated (Hutton and readily inoculate food or water, allowing high inoculum Chase, forthcoming, volume 7). Simple handwashing procedures 174 Reproductive, Maternal, Newborn, and Child Health significantly reduce transmission rates in health care or water disinfection groups. When reenrolled in a facilities (Bolon 2011); households (Bloomfield 2003); follow up surveillance 18 months later, handwashing schools (Lee and Greig 2010); and even day care and pre intervention households were still 1. During weekly follow up throughout the 14 Provision of soap to an urban squatter community months without active educational intervention there in Karachi, Pakistan, supported by weekly meetings with was no difference between the groups in the proportion trained health care workers from the same communities of person days with diarrhea (1. In the critical question is not whether improving hand Bangladesh, the risk of diarrhea diminished when care washing practices is effective, but rather how to best givers washed both hands with water before preparing promote consistent behavior. Risk from health care workers is useful, but how much is was also reduced when caregivers washed hands with feasible and affordable remains in question. Increasingly, soap after defecation, but not with water alone (odds integrated behavioral models will be needed to improve ratio 0. Direct observations identified more than To ensure optimal care of infants and children with 20 opportunities per day for handwashing, a frequency diarrheal disease, caregivers must recognize there is a considered impossible to achieve, especially when the problem, know what to do and do it, be alert to signs added cost of soap is considered. Handwashing after of clinical deterioration needing professional care, and contact with feces is poorly practiced globally (Freeman know how to access such care without delay. Knowledge and others 2014), and Luby and others (2011) recom and experience are necessary but not sufficient; caregivers mended prioritizing handwashing before food prepara must also have the authority to act promptly. Initiatives tion because it was the single most effective opportunity to scale up prompt decision making and action generally to reduce diarrhea risk. These factors may influence whether a caregiver pared provision of soap for handwashing with a method recognizes that fluid losses are beyond normal limits, are to disinfect water or no intervention, including weekly becoming dangerous, and require professional interven visits over nine months to encourage either practice tion (Larrea Killinger and Munoz 2013). The study documented a Higher levels of education promote quicker care 55 percent reduction in diarrhea (95 percent confidence seeking action; however, cultural influences, for example, interval 17 percent to 80 percent) compared with con gender discrimination, can delay action for female infants trol neighborhoods, but no difference between the soap (Malhotra and Upadhyay 2013). In rural Burkina Faso Diarrheal Diseases 175 caregivers failed to recognize mild diarrhea, especially toddlers must be handled safely as well. Because water among infants, and made intervention choices that were and sanitation improvements are often implemented not clinically based and recommended (Wilson and together, separating the influence of each, and under others 2012). In rural Kenya, where munities mobilize to achieve total abandonment of open caregivers understood the significance of diarrhea and defecation and replace it with subsidized construction of dehydration, their primary concern was stopping the facilities, household by household. Cost of treatment is the understand the health implications of open defecation, major pragmatic impediment to care seeking outside and convince the community to join together, without of the home (Nasrin and others 2013). Anthropological external resources except guidance and facilitation, to and ethnographic approaches may help improve edu agree on and act to completely eliminate open defe cational messaging and responses, but cost, travel and cation and build a community sanitary infrastructure access to facilities, and wait times are likely to be critical (Kar 2003). Its relevance is suggested by an analysis of determinants of behavior, and these require very differ Demographic and Health Survey data indicating that ent inputs to address. A 20 percent reduction in open defecation pre care workers means that many children fail to receive dicted a 0. However, a systematic review (Das, Lassi, nity or village to promote understanding of the link and others 2013) concludes that community based between open defecation and illness. Initial engagement interventions improve care seeking by 9 percent (rela is followed by a survey and mapping of actual practices, tive risk 1. In the process, the 29 fold increase in use of zinc supplements (relative risk facilitator may provoke people through? tactics that 29. Although the practices of neighbors and communities, a systems some have criticized the use of shame or social stigma approach to increase attention to multiple transmis to promote compliance (Bartram and others 2012), sion pathways, and highlight the need to widen the others have noted that shame, social pressure, and peer causal lens and pay more conceptual attention to socio monitoring with government subsidies to build latrines economic status, gender, remoteness, and ecosystem markedly increases the adoption of improved sanitation changes? (Eisenberg and others 2012, 242) can improve (Pattanayak and others 2009). For how to promote learning by doing; careful training of full impact, children and adults must learn to consistently facilitators; cultural changes in institutional environ use improved sanitation, and stools from infants and ments to a more participatory, responsive, transparent, 176 Reproductive, Maternal, Newborn, and Child Health and downward accountability approach; and changing the following is a brief discussion of the from a top down to a bottom up development model cost effectiveness of selected diarrhea interventions. The sec others 2006), the ranking of various modalities has ond most cost effective group includes rural sanitation, changed because of new evidence on the benefits of piped water, and in selected countries, cholera vaccine. Such evident that breastfeeding promotion reduces diarrhea, interventions tend to have very heterogeneous results; this practice has not been as high on the research and the one reviewed here (see table 10. Diarrheal Diseases 177 (Borghi and others 2002), falls into the most cost effective Most of the results in tables 9.

However prehypertension hypertension purchase 0.25mg lanoxin overnight delivery, there are instances in the family Pseudoviridae and the family Metaviridae in which one fnds two closely related viruses inhabiting the same host species blood pressure systolic diastolic buy lanoxin no prescription. The question then arises whether these represent different species or more sub tle variants blood pressure young living purchase lanoxin from india. We have considered such viruses separate species if at least one of the major coding regions blood pressure of athletes generic 0.25mg lanoxin with amex. However arteria3d - fortress construction pack order 0.25mg lanoxin with mastercard, the C terminal deletion mutant containing residues 1?381 of the Gag protein is less het erodisperse than the wild type blood pressure medication that does not cause joint pain purchase lanoxin with a visa, and cryo electron micrographs of these particles reveal a surface structure with icosahedral symmetry (Figure 1). The mean radius of the virions is 20?30 nm for wild type and 20 nm for the much better characterized and more uniform 1 381 mutant. A second minor transcript is reported to be 3? coterminal with the major transcript and is most clearly observed in yeast strains with spt3 mutations. These spt3 mutations eliminate or greatly reduce the abundance of the full length transcript. Biological properties Retrotransposon Ty1 is best thought of as a genome parasite of Saccharomyces cerevisiae. In typical wild strains of this yeast, 3?15 copies of Ty1 are found per haploid genome, whereas in typical lab oratory isolates, there are 25?40 copies. Ty1 appears to be restricted to this host species and to very closely related species of Saccharomyces, but is absent from more distant species of the genus. Transmission is likely to be exclusively vertical, and horizontally through conjugation. Ty1 and/or the closely related species, Ty2, has been found in virtually all isolates of S. Some strains contain large numbers of Ty1 virus particles and are otherwise normal in every way. However, overexpression of Ty1 proteins leads to slow growth, but this phenotype is poorly characterized. List of other related viruses which may be members of the genus Pseudovirus but have not been approved as species None reported. However, rela tively little is known about the detailed mechanism of this reaction. Both Gag and Gag Pol primary translation products are processed by the cognate protease into fnal products. Their mode of transmis sion is unknown although presumed to be through vertical inheritance. List of other related viruses which may be members of the genus Hemivirus but have not been approved as species None reported. A reverse transcriptase phy logenetic tree separates the sireviruses from pseudoviruses and hemiviruses (Figure 4). However, stop codon suppression does not seem to be utilized by the other viruses. A unifying characteristic of this genus is that in all members, the gag gene is nearly twice the size of gag encoded by pseudovi ruses and hemiviruses. Sirevirus rice maize gag pol (Opie 2) gag pol gag pol env like gag pol env like gag pol env like Figure 3: Examples of variability in the genome organization of members of the genus Sirevirus. Members of the genus Pseudovirus are shown in red, Hemivirus in blue and Sirevirus in green. Tpv2 6 is an unassigned species and Osr7 and Osr8 have not yet been classifed but clearly belong with the sireviruses. Bousios, Institute of Agrobiotechnology, Centre for Research and Technology Hellas, Thessaloniki, 57001, Greece. Similarity with other taxa Like the families Hepadnaviridae and Metaviridae, the Pseudoviridae are clearly related to the family Retroviridae. All four families are linked by reverse transcription and a viral core structure made up of Gag like proteins. An important and controversial question is the extent of the relationship between the families Pseudoviridae, Metaviridae and the Retroviridae. Because the genomic structures of viruses in fam ilies Pseudoviridae and Metaviridae are clearly related to , but typically simpler than the viruses in the family Retroviridae, many authors who have considered the problem have concluded that the families Pseudoviridae and Metaviridae represent more primitive groups; the family Metaviridae probably spawned the members of the family Retroviridae (presumably by incorpo rating genes encoding ligands for cell surface receptors). An alternative viewpoint that cannot be ruled out, but for which there is less support, is that members of the family Metaviridae represent degenerate forms of the family Retroviridae. While over 100 reverse transcriptase sequence were used to generate this phylogeny, to simplify visual comparison of the major topologies of the tree, viruses from the same class that are located on the same branch of the tree are indicated by an oval. The length of the oval corresponds to the most divergent viruses within that oval. Pseudo: from Greek pseudo, false?, to connote some uncertainty as to whether these are true viruses. Origin and evolution of retroelements based on their reverse transcriptase sequences. The apparently spherical nucleocapsid (nucleoid) is eccentric for members of the genus Betaretrovirus, concentric for members Figure 1: Structure of retrovirus particles. Historically, a nomenclature based on electron micros copy classifed members of the Alpharetrovirus and Gammaretrovirus genera, which assemble their immature capsids at the plasma membrane, as C type viruses. There are 3?6 internal, non glyco sylated structural proteins (encoded by the gag gene). Members of the Spumaretrovirinae encode only a single Gag protein which is cleaved once near the carboxyl terminus in about half of the proteins. The complex retroviruses in the Deltaretrovirus, Epsilonretrovirus, Lentivirus and Spumavirus genera also encode non structural proteins. Infectious viruses have four main genes coding for the virion proteins in the order: 5? Some retroviruses contain genes encoding non structural proteins important for the regula tion of gene expression and virus replication. These cellular sequences are inserted either into a complete retrovirus genome. Such deletions render the virus replication defective and dependent on non transforming helper viruses for production of infectious progeny. In many cases the cell derived sequences form a fused gene with a viral structural gene that is then translated into one chimeric protein. The receptors for gammaretroviruses are involved in the transport of small molecules and have a complex struc ture with multiple transmembrane domains. Subsequent early events are carried out in the context of a nucleoprotein complex derived from the capsid. Reverse transcription is thought to follow the same pathway in members of the subfamily Spumaretrovirinae, but the timing is different as it occurs during viral assembly and/ or release from the cell. The mechanism of reverse transcription allows for high rates of recom bination and genetic diversity for many of the retroviruses. The high rate of genetic variation in vivo can lead to formation of a quasispecies consisting of a large number of genetically diverse virions. However, once integrated, a sequence is apparently incapable of further transposition within the same cell. Most primary translation products in retrovirus infections are polyproteins that require proteolytic cleavage before becoming functional. The gag, pro and pol gene products are generally produced from a nested set of primary translation products. For pro and pol, translation involves bypassing translational termination signals by ribosomal frameshift ing or by readthrough at the Gag Pro and/or the Pro Pol boundaries. Capsids assemble either at the plasma membrane (for a majority of the genera), or as intracyto plasmic particles (for members of the genera Betaretrovirus and Spumavirus) and are released from the cell by a process of budding. Budding appears to occur preferentially at specialized membrane microdomains known as lipid rafts. Polyprotein processing of the internal proteins occurs concomitant with or just sub sequent to the maturation of virions of members of the subfamily Orthoretrovirinae. Antigenic properties Virion proteins contain type specifc and group specifc determinants. Some type specifc determi nants of the envelope glycoproteins are involved in antibody mediated virus neutralization. Group specifc determinants are shared by members of a serogroup and may be shared between members of different serogroups within a particular genus. There is evidence for weak cross reactivities between members of different genera. Epitopes that elicit T cell responses are found on many of the structural proteins. Antigenic properties are not used in classifcation of members of the family Retroviridae. Biological properties Retroviruses are widely distributed as exogenous infectious agents of vertebrates. Endogenous proviruses that have resulted at some time from infection of germ line cells are inherited as Mendelian genes. The vast majority have suffered inactivating mutations and cannot produce infectious virus. A few can exert signifcant biological effects following activation, either by replication in a manner indistinguishable from exogenous viruses or following recombination with replication competent virus. Transmission of retroviruses is horizontal via a number of routes, including blood, saliva, sexual contact, etc. The viruses have a widespread distribution and include both exogenous (vertical and horizontal transmission) and endogenous viruses of chickens and some other birds. Virus infections are asso ciated with malignancies and some other diseases such as wasting, and osteopetrosis. Species demarcation criteria in the genus the list of species demarcation criteria is: l Differences in genome sequence l Differences in gene product sequences DaneshGroup. For example, isolates of avian leukosis virus can be readily distinguished from those of Rous sar coma virus because they lack oncogene sequences while encoding gag, pol and env. The replication defective alpharetroviruses can be distinguished from Rous sarcoma virus by the variable deletion of portions of the gag, pol and env genes and the presence of a unique oncogene in each species. Rous sarcoma virus strains encode the src oncogene, whereas avian myeloblastosis virus, for exam ple, encodes the myb oncogene. List of other related viruses which may be members of the genus Alpharetrovirus but have not been approved as species None reported. Other members of the genus have a D type? mor phology with fewer dense surface spikes and a cylindrical core. Capsid assembly occurs within the cytoplasm (to yield structures previously termed A type? particles) prior to transport to , and bud ding from, the plasma membrane. The sag gene is absent from other members of the genus, but several other viruses encode activities analogous to Rem. The R sequence (15 nt) and the U5 region (95?120 nt) are of similar length in all members of the genus. Viruses assigned to this genus include exogenous (milk transmitted) and endogenous viruses of mice, as well as exogenous, horizontally transmitted and endogenous viruses of New and Old World pri mates and sheep. Murine viruses are associated with mammary carcinoma and T lymphomas, whereas the exogenous primate viruses are associated with immunodefciency diseases; Jaagsiekte sheep retro virus is associated with pulmonary cancer of sheep. Species demarcation criteria in the genus the list of species demarcation criteria is: l Differences in genome sequence l Differences in gene product sequences l Differences in natural host range. Several primate retroviruses have been described that appear to be divergent members of a single virus that arose from a recombination event in which the env gene of a primate gammaretrovirus was captured. Several serologically distinct strains exist within the species Mason?Pfzer monkey virus. Jaagsiekte sheep retrovirus is also assigned to a separate species on the degree of nucleotide sequence divergence. Related endogenous proviruses have been identifed in other mammalian species (rodents and primates). List of other related viruses which may be members of the genus Betaretrovirus but have not been approved as species None reported. Capsid assembly occurs at the inner surface of the membrane at the same time as budding. The pro pol region is translated following ribos omal readthrough at the gag gene termination codon. Some gammaretroviruses additionally trans late the gag region from an upstream initiation codon, yielding a larger, glycosylated form of Gag protein, glyco gag. The viruses are widely distributed; exogenous (vertical and horizontal transmission) and endog enous viruses are found in many mammals. The reticuloendotheliosis viruses comprise a few iso lates from birds with no known corresponding endogenous relatives. The viruses are associated with a variety of diseases, including malignancies, immunosuppression, neurological disorders. Many oncogene containing members of the mammalian and reticuloendotheliosis virus groups have been isolated. Viruses resulting from recombination between exogenous and endogenous viruses are frequently encountered. Species demarcation criteria in the genus the list of species demarcation criteria is: l Differences in genome sequence and viral oncogenes l Differences in antigenic properties l Differences in natural host range l Differences in pathogenicity There are mammalian, reptilian and avian (reticuloendotheliosis) viruses. The mammalian viruses include replication competent viruses, which lack cell derived oncogenes, and replication defective viruses, which have acquired a variety of oncogenes from their hosts. Murine sarcoma viruses, which are invariably replica tion defective, can be distinguished from the murine leukemia viruses and from one another by the presence of distinct cell derived oncogenes. The exogenous viruses (horizontal transmission) in this genus are found in only a few groups of mammals.

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As such arrhythmia beta blockers purchase 0.25mg lanoxin with mastercard, the meat pieces can vary in pH at the higher end of endpoint cooking temperatures blood pressure glucose chart 0.25 mg lanoxin with visa, some and myoglobin content prehypertension lisinopril buy lanoxin 0.25 mg low price. Color reversion also can occur as the result of the formation of the persistent pink associated with undenatured pigments is reduced prehypertension pubmed purchase generic lanoxin pills, denatured globin hemochromes blood pressure record card purchase lanoxin canada. When storing cooked blood pressure 88 over 60 discount lanoxin 0.25 mg overnight delivery, primarily an issue with the internal color of the product because intact beef in the absence of oxygen, this pigment can form the outer regions of the product would be more thoroughly as a result of the cooking that denatures myoglobin (binding cooked than the internal area. In contrast, persistent pink site on heme iron more available) and reaction with various formed by reduced, denatured globin hemochromes may be an nitrogen containing compounds, as described in the occurrence issue on the surface as well as internally in the cooked product. Color Pink color present on the outer surface and extending only a Photo 3: Example of Color Reversion 10 Minutes After Cooking and Slicing. Nitrogen dioxide may be present as breast meat during fuel combustion byproducts in gas fred ovens leading to the refrigerated storage formation of a pink ring (Cornforth et al. If the pink color is within the beef product, species, cytochrome c nitrosylhemochrome may also be present as a result of may be involved (Ahn unintended contamination of the product with nitrite in water and Maurer, 1990). Cytochrome c can An internal pink color can also be formed by the reaction of undergo color reversion various nitrogen containing substances with the denatured meat Picture courtesy of the University of after heat processing and pigment. Nicotimamide denatured globin hemochromes found Wisconsin Madison Meat Science and the product is cooled and in tuna and poultry (Brown and Tappel, 1957; Claus et al. For these types of reduced, color reversion in beef because beef contains signifcantly higher denatured globin hemochromes to form, the native structure of levels of myoglobin and hemoglobin, which dominate the color the protein portion must be denatured to open up the binding site of the meat. In addition, the iron in the heme ring must be in the reduced Conclusions state (ferrous iron) in order to bind these compounds. Color and heat affect the color include: pigment concentration, chemical state denaturation of myoglobin forms in ground beef. Effects of endpoint temperature, pH, and storage time on safety risk on their own. Using color as an indicator of adequate cooked internal color reversion of pork longissimus chops. Internal a meat thermometer and knowledge of recommended internal premature browning in cooked ground beef patties from high temperatures remains the most accurate method to determine a oxygen modifed atmosphere packaging. The storage life of beef and pork packaged in an atmosphere with low carbon References monoxide and high carbon dioxide. Pink color oxidative state affects internal cooked color development in development in turkey meat as affected by nicotinamide, ground beef patties. Carbon monoxide, nitric oxide, and nitrogen dioxide levels in gas ovens related to surface pinking of cooked beef and turkey. Most causes can simply be seen as pinkish urine, but other times it can are not serious, but some could be, like cancer. With hematuria, you may Hematuria can be from a non serious (benign) cause: not have other symptoms, or you may feel pain. Sickle cell disease from anywhere in the urinary tract, from the kidney to the urethra. Hematuria is managed by treating its underlying cause: Health care providers will frst ask about your health. A menstruation (period), kidney stones, drugs, smoking or follow up urinalysis should be done after treatment. Urine tests will be ordered, maybe over a important to confrm that the infection is gone. Then the urine must be or blood disorders, then your treatment plan should be looked at under a high powered microscope to diagnose followed carefully. The urine can be tested to fnd cancer cells, oncologist or oncology surgeon may help. For example, this test bladder tumor is found early, the cancer can often be cured. For American Urological Association example, high levels of the protein creatinine, shows Asymptomatic Microhematuria Guideline kidney disease. If blood You may download this fact sheet and print it at is still seen, tests may be repeated until the cause is found. For copies of other printed materials about urologic conditions, visit UrologyHealth. It helps to work closely with your health care provider to learn the cause to treat the problem. Anemia is a readily identifiable surrogate associated with high rates of adverse clinical outcomes. Maintains fuid and electrolyte balance pizza, canned soups, table salt Pregnancy: 1,500 mg. Breast feeding: 1,500 mg and muscle contraction the tolerable upper intake level for sodium is 2,300 mg, Adults over 50: 1,300 mg. Adults over 70: 1,200 mg * the amount found in about 2/3 tsp of table salt Zinc Oysters, beef, crab meat, dark meat chicken Men: 11 mg. Assists in hundreds of enzyme reactions and turkey, pork, yogurt, milk, cashews, Women: 8 mg. Assists in hemoglobin production chickpeas, almonds, peanuts, cheese Pregnancy: 11 mg. Describe the distribution & morphology of cells in certain common Blood Pictures? Clinical Diagnostic Laboratories offer: 1. It will include preconceptual screening and antenatal, intrapartum and postnatal management. All of these genotypes will give a similar clinical phenotype of varying severity. These cells are prone to increased breakdown, which causes the haemolytic anaemia, and to vaso occlusion in the small blood vessels, which causes most of the other clinical features, including acute painful crises. The National Library for Health and the National Guidelines Clearing House were also searched for relevant guidelines. Where possible, recommendations are based on available evidence; areas where evidence is lacking are annotated as good practice points (designated by a tick). This consultation should include optimisation of management and screening for end organ damage. Primary care physicians have a key role in preconceptual screening, including the provision of P contraceptive advice. P Reproductive planning and contraceptive choice should be part of the regular outpatient consultation in the sickle cell clinic. Renal and liver function tests should be performed annually to identify sickle nephropathy and/or deranged hepatic function. In women who have been multiply transfused in the past or who have a high ferritin level, T2* cardiac magnetic resonance imaging may be helpful to assess body iron loading. Aggressive iron chelation before conception is advisable in women who are significantly iron loaded. Red cell antibodies may indicate an increased risk of haemolytic disease of the newborn. If identified as an at risk couple?, as per National Screening Committee guidance, they should receive counselling and advice about reproductive options. General practitioners have a key role to play in partner screening and genetic counselling. Women should be encouraged to have the haemoglobinopathy status of their partner tested. If a partner is a carrier of, or affected by, a major haemoglobinopathy, the couple should receive appropriate counselling regarding the risk of having affected offspring (Table 1). Partners will not always be available or willing to undergo preconceptual testing. Folic acid (5 mg) should be given once daily both preconceptually and throughout pregnancy. D 39 Evidence Folic acid is recommended in all pregnant women to prevent neural tube defects. Hydroxycarbamide (hydroxyurea) should be stopped at least 3 months before conception. D Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be stopped before D conception. Persistent vomiting can lead to dehydration and sickle cell crisis and women should be advised to seek D medical advice early. The influenza vaccine should be recommended if it has not been administered in the previous year. Therefore, all of the actions outlined in section 4, including vaccinations, review of iron overload and red cell autoantibodies, should take place as early as possible during antenatal care. The development of multidisciplinary care seems to be associated with an improvement in maternal and fetal outcomes. If there is a relevant multidisciplinary team available within reasonable travelling distance, women should go there. If this is not available, women should be cared for by high risk? teams who have shared care arrangements and shared protocols with the specialist teams. Partner status and subsequent counselling should be clearly documented in the notes. The objective of the screening programme is to ensure that screening tests are offered by 8?10 weeks of pregnancy by primary care or maternity services. If women have not undergone a preconceptual review, they should be advised to take daily folic acid and D prophylactic antibiotics (if not contraindicated). Iron supplementation should be given only if there is laboratory evidence of iron deficiency. Women who are at increased risk of pre eclampsia are advised to take low dose aspirin 75 mg from 12 weeks of gestation, unless they have aspirin sensitivity. Blood pressure and urinalysis should be performed at each consultation, and midstream urine for C culture performed monthly. Women with pre existing proteinuria or known renal impairment will require more frequent monitoring. Studies have also demonstrated an increase in the incidence of urinary tract infection and asymptomatic bacteriuria,26 so urinalysis should be performed at each antenatal visit and midstream urine should be sent for culture and sensitivity monthly. At each appointment, opportunities should be offered for information and education. P Women should be offered the routine first trimester scan (11?14 weeks of gestation) and a detailed P anomaly scan at 20 weeks of gestation. In addition, women should be offered serial fetal biometry scans (growth scans) every 4 weeks from 24 weeks of gestation. Serial growth scans allow early detection of fetal growth restriction and hence aid level 2+ appropriate timing of delivery to reduce perinatal mortality and morbidity. A If acute exchange transfusion is required for the treatment of a sickle complication, it may be D appropriate to continue the transfusion regimen for the remainder of the pregnancy. Blood should be matched for an extended phenotype including full rhesus typing (C, D and E) as well A as Kell typing. P Early studies recommended prophylactic transfusion during pregnancy as there was a decrease in Evidence maternal morbidity and perinatal mortality among transfused women compared with historical level 1 controls. A randomised controlled trial59 and a retrospective study25 have Evidence demonstrated that prophylactic transfusion decreased the incidence of maternal painful crises but level 1 did not influence fetal or maternal outcome. A systematic review60 indicated that there is insufficient evidence to draw conclusions about the role of transfusion in pregnancy. There is no absolute level at which transfusion should be level 4 undertaken and the decision must be made in conjunction with clinical findings, but haemoglobin under 6 g/dl or a fall of over 2 g/dl from baseline is often used as a guide to transfusion requirement. Alloimmunisation is clinically important as it can lead to delayed haemolytic transfusion reactions or haemolytic disease of the newborn62 and can render patients Evidence untransfusable. D Pregnant women presenting with acute painful crisis should be rapidly assessed by the D multidisciplinary team and appropriate analgesia should be administered. Women admitted with sickle cell crisis should be looked after by the multidisciplinary team, involving D obstetricians, midwives, haematologists and anaesthetists. The requirement for fluids and oxygen should be assessed, and fluids and oxygen administered if D required. Thromboprophylaxis should be given to women admitted to hospital with acute painful crisis. Primary care physicians should have a low threshold for referring women to secondary care; all women with pain which does not settle with simple analgesia, who are febrile, have atypical pain or chest pain or symptoms of shortness of breath should be referred to hospital. History should ascertain if this is typical sickle pain or not, and if there are precipitating factors. Examination should focus on the site of pain, any atypical features of the pain and any precipitating factors, in particular whether there are any signs of infection. Initial investigations should include full blood count, reticulocyte count and renal function. Other investigations will depend on the clinical scenario but may include blood cultures, chest X ray, urine culture and liver function tests. Initial analgesia should be given within 30 minutes of arriving at hospital and effective analgesia Evidence should be achieved within 1 hour. Weak opioids such as co dydramol, co codamol or dihydrocodeine can be used for moderate pain, and stronger opiates such as morphine can be used for severe pain. Parenteral opiates can be given by intermittent bolus or patient controlled administration systems. If the women need strong opiate therapy, they will need to be admitted to hospital: to a medical ward in early pregnancy, or to a level 2 antenatal bed in later pregnancy, under the joint care of obstetricians and haematologists. Assessments of pain score, sedation score and oxygen saturation should be performed at least 2 hourly using a modified obstetric early warning chart. Outline of management of acute pain Rapid clinical assessment If pain is severe and oral analgesia is not effective, give strong opioids.

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The members of the Group as well as the terms of reference are shown on pages 2 and 7 blood pressure on forearm buy lanoxin 0.25 mg lowest price. Acknowledgements the Ad Hoc Group wishes to thank all the organisations and individuals heart attack nightcore order discount lanoxin on line, detailed at Annex 1 blood pressure medication and zinc buy cheap lanoxin line, who provided it with information or gave oral evidence blood pressure gradient lanoxin 0.25mg low price. Where the Ad Hoc Group considered that a recommendation from the previous report needed to be re iterated this is shown on the enclosed table heart attack zippy demi generic lanoxin 0.25mg. We strongly recommend that hypertension yeast infection purchase cheap lanoxin line, for cases of infection fulfilling Kaplan criteria, control measures are instituted immediately without waiting for laboratory confirmation although confirmation of diagnosis in due course is desirable. For example, In practice there appears to be continuing uncertainty on the level of evidence needed to initiate control measures (such as closure of oyster production areas). In practice this investigation and reporting of recommendation appears not to cases of food poisoning in the have been addressed. The most commonly identified pathogens were norovirus (16% of samples tested), Page 14 of 136 sapovirus (9. Chapter 4: : Detection methods for viruses in clinical samples and foods Recommendation R4. In addition, certificated Pathology Accreditation reference materials are now scheme. These advances should be utilised by food testing laboratories to ensure robust analysis. Page 15 of 136 Chapter 5: Viral contamination of food, routes of spread and vehicles, prevention and control measures Recommendation R5. If necessary, there should be more research into the effectiveness of viral inactivation. It is already investigate the effect of washing on virus funding work on viruses and removal from a range of fruit and on methods for cleaning fruit vegetables. There is a need to review the available literature in this area to assess the likely effectiveness of measures such as physical and chemical treatment for controlling norovirus in the food chain: We will also consider objectives within the foodborne virus research programme and future Agency work in this area. They generally effective enforcement and have limited information on the use of such guides supports the Industry Guides to Good measures relevant to food virus proportionate, consistent and effective Hygiene Practice have to play contamination. The main specific application of food hygiene legislation and in public health protection. The Mail Order Guide talks about removing infected food handlers from handling food but does not include information on exclusion times or reference further details. They should provide clear interpretation of exactly what is needed by way of training, personal hygiene standards and effective exclusion of symptomatic and post symptomatic food handlers. Guides which do not provide clear guidance in these areas should not be recognised. A Government setting out the process and criteria for the Guide and the Catering Guide Template provides guidance development and recognition of these Ships. Information on personal hygiene tends to be basic and often does Page 18 of 136 not consider what is needed in terms of good hand washing. As this is a key infection control measure this should be addressed in new guides and addressed separately where there are existing guides. The major omission is the Catering Guide and given the risk of viral infection on ships, the Ships Guide. We understand that the latest version of the Fresh Produce Guide was published in 2009. The status, enforceability and effectiveness of guides should be kept under review. Its main focus is on Where a food business operator is copies of Guides are also outbreak management. It notes following a recognised industry guide, the provided to all local authority Occasionally food may be enforcement authority must take this into environmental health implicated in viral trans mission. It account when assessing compliance with departments with a request to identifies the need to exclude the legislation. Investments to meet guideline) still seems a remote bathing waters or the Urban Waste Water Treatment prospect for the majority of areas. The percentage of prohibited and class C Environment Agency is harvesting areas from 34% in 1998 to required, for discharges 10% Class C beds in 2012. We deterioration in water quality recognise that this could go further and should normally be allowed Defra commissioned a research contract which would be expected to to clarify the relationships between cause deterioration in microbial levels in the water column and classification. This reported in in the quality of bathing waters Spring 2013 and showed that shellfish and implementation of the biomagnify microbial pollution significantly Urban Waste Water Treatment more than expected. Previously, and a formal Working Group has meetings have been held on not been established. However, announced further designation kept a broad match between harvesting it remains unclear what protection of shellfish waters in Scotland areas and shellfish waters in terms of and improvement will result from under the Shellfish Waters areas covered. The commitment in the Water for Life white Government considers that the paper to maintain a similar level of protection of shellfish protection under the Water Framework populations can be most Directive. It is set as 10 spills per annum, formulation of a Government policy programme of prioritising annualised over a 10 year period to allow in line with the recommendation. This is of existing unsatisfactory particular concern considering discharges improved. Water companies should provide the local Food Authorities with summaries of the operation of storm discharges in the vicinity of shellfish beds and of all emergency discharges immediately they occur. Following a discharge, Food Authorities should take sufficient samples to determine the extent of contamination so that, if necessary, they can prevent harvesting for a period, either by voluntary agreement from harvesters or by using statutory powers. Some programme provides research programme is available at: aspects, for example the behaviour opportunity for collaborative of viruses during depuration, could. The Government standardised quantitative methods ramme/ would welcome relevant for norovirus are available. B04002: Development of procedures for improved viral reduction in oysters during commercial depuration (published April 2004). Delegates attending this event were also given the opportunity to comment on the research presented but also on future concerns and areas for investigation. A summary note of the B16 Programme Review including the key outputs is available at: This project addressed a major issue regarding foodborne viruses and the lack of effective risk management strategies and prevention measures against food and environment contamination. The current epidemiological surveillance systems can only react to and provide information on disease outbreaks that occur through contamination of food. It is important to note these actions will still not guarantee freedom from noroviruses, but should help minimise risks. Characteristics of viruses Viruses are very small micro organisms ranging in size from 20nm to 400nm in diameter. Unlike bacteria they are not free living and only replicate within the living cells of humans, animals, plants or bacteria. Foodborne viruses of concern the important viruses linked to foodborne transmission are shown in Table 2. Norovirus gastroenteritis is the most commonly recognised foodborne viral infection through consumption of shellfish and fresh produce and following contamination by infected food handlers. Hepatitis A has also been linked to these routes of transmission but has been infrequently recognised in recent times. Hepatitis E is an increasingly recognised foodborne illness associated with the consumption of processed pork and has also been associated with the consumption of game meat (Legrand Abravanel et al, 2010) and shellfish (Said, 2009). These viruses are shed in high concentrations in faeces and vomit and remain infectious in the environment for several days or months (Koo, Ajami et al, 2010). Animal viruses often replicate poorly in the human host but the incidental co infection of a host with animal and human viruses may result in the mixing of virus genes, through recombination or reassortment (Iturriza Gomara, Isherwood et al, 2001; Banerjee, Iturriza Gomara et al, 2007). This may allow the emergence of progeny viruses with the replicative advantage of the human virus and possessing novel antigens conferred by the animal virus. A wide range of other viruses are shed in faecal specimens and therefore may have the potential to cause foodborne illness. These will not be considered further because their role in human infection and disease is not established. Viruses falling into this category include: aichi virus, bocavirus, cardiovirus, cosavirus, klassevirus, picobirnavirus and torovirus (Van Leeuwen, 2010; Neilson, 2013; Kapusinszky, 2012). Gastroenteritis viruses Virus Clinical Epidemiology routes of Burden of Considered or not Presentation transmission foodborne illness considered in report Norovirus Gastroenteritis Faecal oral transmission Estimate 200,000 Considered because mostly person to person. Shellfish, fresh produce and food handler related outbreaks are commonly reported. Rotavirus Gastroenteritis Routes of transmission as Few case reports Not considered Astrovirus Gastroenteritis norovirus, but most Sapovirus Gastroenteritis infection is found in Adenovirus Gastroenteritis infants. Outbreaks are Group F rarely recognised because of acquired immunity in childhood. Hepatitis viruses Virus Clinical Epidemiology routes of Burden of Considered or not Presentation transmission foodborne illness considered in report Hepatitis A Acute hepatitis Faecal oral transmission, Well documented Considered because now low incidence in west outbreaks. Sporadic high burden of disease Europe, but high cases linked to fresh population susceptibility, produce increasingly commonly travel and recognised. Picornaviruses Virus Clinical Epidemiology routes of Burden of Considered or not Presentation transmission foodborne illness considered in report Coxsackie A, Meningitis, Faecal oral transmission Not considered B Upper but outbreaks not Enteroviruses Respiratory recognised because of Paraechovirus Tract Infection, low clinical attack rate. New and Emerging viruses Virus Clinical Epidemiology routes of Burden of Considered or not Presentation transmission foodborne illness considered in report Nipah virus Encephalitis All can be found in animal Considered because tissues; main risk is direct of potential risks. All 3 viruses Influenza Tract Infection cause severe illness high mortality but limited human to human transmission reported. The virus is non enveloped, 30 35nm in diameter and has an icosahedral structure (Gray and Desselberger, 2009). The viruses are very diverse and characterised into 5 genogroups of which 3 infect humans. The virus is stable in the environment and may be resistant to inactivation by solvents and many disinfectants (Duizer, Bijkerk et al, 2004). Norovirus is highly infectious with a low infectious dose of approximately 10 virus particles. During the Page 28 of 136 7 acute phase of the illness virus is excreted in faeces at concentrations of ~10 particles per gram or ml. It can be transmitted by person to person spread, waterborne infection following exposure to contaminated drinking or recreational waters, the ingestion of contaminated foods such as uncooked shellfish, berries and salads or contact with contaminated surfaces. The incubation period for norovirus infection is 10 50 hours and symptoms include the rapid onset of nausea, headache and abdominal cramps followed by diarrhoea and vomiting, often projectile, and lasts for only 12 to 48 hours. Immunity, even with homologous viral challenge, is short lasting with infected individuals becoming susceptible to subsequent norovirus infections after ~6 12 months. The sapovirus genome, which can be divided into at least five genogroups (I to V) based on complete capsid sequences, is highly diverse. Sapovirus epidemiology shows some similarity to that of norovirus, but a much lower scale of foodborne infection is recognised. It is serologically monotypic but classified by sequence variation into genotypes, at least 5 (1A, 1B, 3A, 3B, 7) of which are seen in human infections. Virions are non enveloped, 27nm in diameter and have an icosahedral structure (Harrison et al, 2009). Anicteric or asymptomatic infections are common in children, whereas, infection in Page 29 of 136 adults results in acute icteric hepatitis in >70% of those infected with a case fatality rate of 0. Prodromal symptoms include fever and headache followed by fatigue, anorexia and myalgia with the development of jaundice of the sclera and skin. The development of jaundice usually heralds a rapid subjective improvement in symptoms. In industrialised countries person to person transmission is rare and outbreaks of hepatitis A infection are associated with spread via contaminated food. The large number of virus particles shed in faeces and the long incubation period in which shedding occurs contributes significantly to outbreaks, particularly those associated with food handlers. Outbreaks are often associated with the consumption of raw or inadequately cooked shellfish cultivated in contaminated waters. Virions are non enveloped 32 34nm in diameter, and are calicivirus like in morphology. Genotype 1 has been isolated from humans in Asia, genotype 2 from humans in Mexico, genotype 3 from humans, swine and other animal species such as wild boar, deer and rodents in Europe and North America, and genotype 4 from humans and swine in East Asia (Teo, 2006). Virus infectivity was completely inactivated after boiling or stir frying for 5 minutes. However, incubation of o contaminated livers at 56 C for 1 hour, equivalent to medium to rare cooking conditions in a restaurant, did not inactivate the virus (Feagins et al, 2008). Heating o to an internal temperature of 71 C for at least 5 minutes (see Section 8. Babies born to women with acute disease are at risk of vertical transmission and associated morbidity and mortality. Page 30 of 136 Recently, sporadic cases of hepatitis E have been reported in individuals with no history of travel to highly endemic areas (Ijaz, 2005). Cases of hepatitis E caused by genotype 3 virus are typically observed in older men and have been related to various animal reservoirs including swine, wild boar, deer and rodents. Emerging viruses In recent years there have been several newly recognised viruses which have raised concern about the risk of transmission through the food chain. Although both pose a theoretical risk it is likely that direct contact with infected animals is the main risk. Similarly, zoonotic viruses such as simian herpes viruses, simian immunodeficiency virus and simian foamy viruses may enter the food chain through the butchering of wildlife to provide bush meat (Cutler et al, 2010; Smith et al, 2012). It is probable that butchering the animal is the high risk activity, as viruses are likely to be inactivated by cooking.

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