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Pregunte a su proveedor de atenciуn mйdica si su hijo necesita recibir medicina para los ojos. Asegъrese de lavar cuidadosamente cualquier cosa que se ponga en contacto con los ojos del niсos (tales como toallitas, toallas, binoculares de juguete y cбmaras fotogrбficas de juguete). If your child develops severe diarrhea, diarrhea with blood or mucous, fever, or vomiting, do not send him/her to the center. The germs are then swallowed by the other person, multiply in their intestines, and cause an infection. This is critical for family or household members who handle or prepare food as a job. Si su niсos contrae una diarrea severa, diarrea con sangre o mucosidad, fiebre o vуmitos, no lo envнe al centro. Lleve a su niсos a su mйdico y pida que se le haga una prueba de heces para detetcar E. Йl/ella probablemente querrб hacer tambiйn una prueba a otros miembros de la familia que tambiйn tengan diarrea. Por favor, mantйnganos informados de cуmo se siente su niсo y sobre las pruebas positivas o tratamiento. Los gйrmenes pueden luego ser esparcidos en los alimentos y bebidas u objetos, y eventualmente, a las manos y bocas de otras personas. Los gйrmenes luego son tragados por otra persona, se multiplican en los intestinos y causan la infecciуn. Esto es crнtico para su familia o miembros del hogar que tratan o preparan alimentos como parte de su trabajo. Fifth disease is a benign rash illness of childhood sometimes called erythema infectious. The illness begins with prodromal phase of mild fever with non-specific symptoms of headache, malaise and muscle aches. The rash begins as a red, flushed appearance on the cheeks, giving a "slapped cheek" appearance. The virus can cause stillbirth and fetal hydrops in pregnant women experiencing a primary infection. La Quinta Enfermedad es una enfermedad de la niсez con erupciуn benigna, algunas veces llamada eritema infecciosa. La enfermedad comienza con una fase prodrуmica de fiebre moderada con sнntomas no especнficos de dolor de cabeza, malestar y dolor de mъsculos. Por favor consulte con su mйdico si estб embarazada y un niсos tiene la quinta enfermedad. El virus puede tambiйn esparcirse en objetos inanimados a niсos que son susceptibles. Las mujeres embarazadas deben consultar con su mйdico para recibir consejo para el tratamiento. Los niсos con la quinta enfermedad no necesitan ser excluidos de la guarderнa, ya que es improbable que sean infecciosos despuйs de la apariciуn de la erupciуn, y el diagnуstico clнnico sea realizado. Watch your child and members of your family for diarrhea, stomach cramps, gas and nausea. If your child develops diarrhea or diarrhea with fever or vomiting, do not send him/her to the center. If the test is positive keep your child home until any serious diarrhea or illness is over and your child has received medication. Giardia is a very small (microscopic) parasite that can infect the intestines and stools. Giardia germs live in the intestines and are passed out of the body into the stools. Obviously, it can spread easily among small children who normally get their hands into everything and may not wash their hands well. Giardia can be diagnosed by a test called "stool culture for ova and parasites", in which the stool is examined under a microscope.

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The licensee shall provide for the safe disposal of water and other chemicals used for cleaning purposes. Disinfectants, cleaning solutions, poisons, and other items which could pose a danger if readily available to clients shall be stored where inaccessible to clients. General permanent or portable storage space shall be available for the storage of equipment and supplies. Pool covers shall be strong enough to completely support the weight of an adult and shall be placed on the pool and locked while the pool is not in use. Where an above-ground pool structure is used as the fence or where the fence is mounted on top of the pool structure, the pool shall be made inaccessible when not in use by removing or making the ladder inaccessible or erecting a barricade to prevent access to decking. If a barricade is used, the barricade shall meet the requirements of Section 82087(f)(1). Sufficient parking area shall be available for safe arrival and departure of participants clients. A space shall be provided for clients not actively participating in the planned activity programs. There shall be space available for storage of equipment and supplies necessary to implement the planned activity program. There shall be space available on the premises for storage of the program records as specified in Sections 82066, Personnel Records, 82068(e), 82068. The licensee shall ensure that the fire clearance includes approval of delayed egress devices. Fire and earthquake drills shall be conducted at least once every three months on each shift and shall include, at a minimum, all direct care staff. Without violating Section 82072(a)(6), program staff shall attempt to redirect a client who attempts to leave the program. Clients who continue to indicate a desire to leave the program site following redirection shall be permitted to do so. The report shall be made by telephone no later than the next working day and in writing within seven calendar days. Delayed egress devices shall not substitute for trained staff in sufficient numbers to meet the care and supervision needs of all clients and to escort clients who leave the program. All toilets, hand washing and bathing facilities shall be maintained in safe and sanitary operating condition. Additional equipment, aids, and/or conveniences shall be provided in day programs accommodating physically handicapped clients who need such items. Each movable bin shall provide for suitable access and a drainage device to allow complete cleaning at the storage area. Based upon the total licensed capacity, one handwashing facility, and one toilet providing individual privacy, shall be maintained for every 15 clients, or fraction thereof. If beds are provided for resting, they shall be arranged to allow for unobstructed passage of personnel and of clients with assistive devices including, but not limited to, wheelchairs and walkers. Bottled water or portable containers shall be permitted provided that: (A) (B) (3) the water and containers are kept free of contaminations. The Department may grant an exception allowing acceptance or retention of a client who has a medical or health condition not listed in Section 82092, Restricted Health Conditions, if all of the following requirements are met: (1) Either the condition is chronic and stable, or it is temporary in nature and is expected to return to a condition normal for that client. The licensee has developed a plan of care for the client as specified in Sections 82068. If the client is unable to care for all aspects of the condition, a licensed professional, or facility staff who receive supervision and training from a licensed professional, may assist the client in the care of the condition. The licensee obtains from the licensed professional written documentation outlining the procedures and the names of facility staff who received the training. The licensee ensures that the licensed professional reviews staff performance as the licensed professional deems necessary, but at least once a year. Any other condition or care requirements which would require the day program to be licensed as a health facility as defined by Health and Safety Code Section 1250. Care for the following health conditions must be provided only as specified in Sections 82092. Requirement for fecal impaction removal, enemas, and suppositories, only as specified in Section 82092. Prior to admission of a client with a restricted health condition specified in Section 82092, the licensee shall: (A) Communicate with all other persons who provide care to that client to ensure consistency of care for the medical condition. Training shall include hands-on instruction in both general procedures and client-specific procedures.

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Conta minated water may also be highly infectious for humans and domestic animals. Depending on the location, size and duration of the outbreak, it can be helpful to establish a field laboratory. This may be a mobile laboratory which is brought in or a local labora tory which is additionally equipped for diagnosing tularaemia. In addition, simple instruments for genetic detection of pathogens under field conditions and biosensors are currently under development. In addition, the field laboratory will be the focal point for the collection and registration of the samples. It may also prepare samples for shipment to specialized laboratories for confirmation or further research such as molecular characterization (see section 6. Although currently not available, vaccination of the human population against tularaemia in endemic regions would be most effective. This pathogen is so infectious by the airborne route that it has been stated that "The hazard of infection with Francisella tularensis is well recognized; few persons escape illness if they continue to work with the organism" (Overholt et al. In a detailed analysis of 34 cases of laboratory-acquired infection it was reported that 20 showed pulmonary involvement (Over holt et al. For the vast majority of these cases, there was no obvious previous exposure of the individual to the pathogen, but the high incidence of pulmonary involvement clearly suggest that most of these individuals contracted the disease after exposure to airborne bac teria (Overholt et al. In most countries, the highly virulent subspecies tularensis will be classified as risk group 3 (high risk for the laboratory worker, but low community risk) while the other subspecies will be clas sified as risk group 2 (moderate risk for the laboratory worker, low community risk (World Health Organization, 2004b). The degree of risk varies not only with the virulence of the organism but also with the material being handled. It is recommended that all handling of clinical samples and cultures suspected to be F. In particular, individuals should be made aware of the possible sources of aerosols and the procedures which minimize the generation of aerosols. In addition, we recommend that new workers are supervised by an experienced individual during their learning phase. Each laboratory should have defined procedures addressing the use of equipment (especially equipment that may generate aerosols); disinfection of equipment and contaminated materials; handling and processing samples; spill containment and clean-up; and waste handling. These procedures should be clearly and concisely written, easily accessible and rigorously followed. A separate room is required with only one entrance; a biohazard notice prohibiting the entry of unauthorized persons should be prominently displayed at the entrance. Ideally, the room should have a double-door entrance designed to provide an airlock. The ventilation should be arranged to maintain the air pressure within the room at a slightly lower level than its surroundings. Air from the room should be discharged to the exterior, well away from air intakes and opening windows, otherwise it must be sterilized by filtration or heat treatment. The walls should be impermeable and all windows sealed to allow disinfestation and fumi gation; it should be safeguarded against infestation with rodents or insects. The air exhaust from the cabinet should be so arranged as to avoid interference with the air balance in the room or within the cabinet when it is switched on. The room should have a sink, an autoclave and enough incubator space for all culture requirements. Biosafety cabinets should be used for all procedures involving human pathogenic strains (including F. These procedures include the growth of bacteria in liquid culture, the growth of large numbers of bacteria. Ideally, items of equipment which might generate aerosols should be contained within a purposebuilt cabinet. Centrifuges may cause dangerous aerosols, especially when tubes containing virulent bacteria break. Glass tubes should not be used for virulent materials, instead polycarbonate tubes with tightly-fitting screw-capped lids and rubber O-rings are recommended. When centrifuges are located outside a biosafety cabinet, the centrifuge rotors should incorporate some form of seal that allows the rotor to be removed and opened only within a safety cabinet.

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All actions taken, including wildlife rehabilitation, should be in concert with those mandated to address oil spills. Human Health Considerations Direct contact with petroleum, handling oiled wildlife, and activities associated with the cleanup are all potentially hazardous to humans. Health impacts due to the toxic effects of petroleum include contact dermatitis, increased skin cancer risk, eye irritation, and problems associated with inhaling volatile components of petroleum products. Many individuals and groups have expertise in the rehabilitation of oiled birds and other wildlife. The use of lead shot for waterfowl hunting within the United States has been prohibited and efforts are underway to ban the use of lead fishing sinkers and prohibit the use of lead shot for nonwaterfowl hunting. Numerous other reports and studies added to those findings during the years and decades that followed. The continued use of lead shot and lead fishing weights and the large amounts of these materials previously deposited in environments where birds feed assure that lead poisoning will remain a common bird disease for some time. These findings demonstrate that lead poisoning can afflict birds even without heavy hunting pressure. With the exception of waterfowl and raptors, lead poisoning from ingesting lead shot is generally a minor finding for other species (Table 43. Lead poisoning due to ingesting lead fishing weights has been reported in numerous species. The greatest number of reports are from swans as a group, common loon, brown pelican, Canada goose, and mallard duck. Laysan albatross chicks on Midway Atoll suffer high lead exposures and mortality from ingesting lead-laden paint chips flecking off of vacant military buildings. Other far less common sources include lead fishing sinkers, mine wastes, paint pigments, bullets, and other lead objects that are swallowed. This disease still affects waterfowl and other species due to decades of residual lead shot in marsh sediments, continued deposition from allowable use of lead shot during harvest of other species, noncompliance with nontoxic shot regulations, target shooting Distribution Losses occur coast-to-coast and border-to-border within the United States. In areas where few birds are examined, the frequency of lead poisoning and other diseases will be underestimated. Several of these countries have implemented nontoxic shot requirements and several others are beginning to address this issue. Special attention should be given to waterfowl that do not take flight when the flock is disturbed and to small groups of waterfowl that remain after most other birds of that species have migrated from the area. Because severely affected birds generally seek isolation and protective cover, well-trained retrieving dogs can help greatly to locate and collect these birds. Gross Lesions Lead-poisoned waterfowl are often emaciated because of the prolonged course of the illness and its impact on essential body processes. Therefore, many affected birds appear to be starving; they are light in weight, have a "hatchet-breast" appearance. Nonendangered species Upland gamebirds Ring-necked pheasant Wild turkey Raptors Golden eagle Red-tailed hawk Wetland birds Common loon White pelican Great blue heron Sora rail Pectoral sandpiper Herring gull Endangered species California condor Bald eagle 1 2 Hungarian partridge Mourning dove Bobwhite quail Scaled quail Northern harrier Prairie falcon Rough-legged hawk Turkey vulture Double-crested cormorant American coot White ibis American avocet Western sandpiper Glaucous-winged gull Greater sandhill crane Royal tern Great egret Black-necked stilt Long-billed dowitcher California gull Lesser sandhill crane Flamingo Snowy egret Marbled godwit Laughing gull Laysan albatross1 Brown pelican Mississippi sandhill crane Whooping crane2 Peregrine falcon the cause of poisoning was ingestion of paint chips rather than lead shot, bullets, or fishing tackle. The cause of poisoning was particulate lead of unknown origin but not lead shot or fishing tackle. Impactions of the esophagus or proventriculus in approximately 20­30 percent of affected waterfowl. The extent of impaction may be restricted to the gizzard and proventriculus, extend to the mouth, or lie somewhere in between. A prominent gallbladder that is distended, filled with bile, and dark or bright green. Pellets that have been present for a long time are well worn, reduced in size, and disk-like rather than spherical. Flushing contents through a series of progressively smaller sieves is one method of pellet recovery. However, none of these signs or lesions is diagnostic by itself and all can result from other causes.

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In a few other cases-Bolivia and Peru, for example- the overall human development outcome appears marginal despite sizeable income gains, suggesting poor access to services as a factor inhibiting well-being. However, these exceptional cases serve to emphasize the norm, which is that most movers are winners. The share of migrants reporting that they felt quite or very happy was highest in developed countries. The broad findings presented in this chapter underline the role of movement in expanding human freedoms that was outlined in chapter 1. We saw that people who move generally do enhance their opportunities in at least some dimensions, with gains that can be very large. However, we also saw that the gains are reduced by policies at home and destination places as well as by the constraints facing individuals and their families. Since different people face different opportunities and constraints, we observed significant inequalities in the returns to movement. The cases in which people experience deteriorations in their well-being during or following the process of movement-conflict, trafficking, natural disasters, and so on-were associated with constraints that prevent them from choosing their place in life freely. A key point that emerged is that human movement can also be associated with tradeoffs-people may gain in some and lose in other dimensions of freedom. However, the losses can be alleviated and even offset by better policies, as we will show in the final chapter. This chapter explores impacts in the country of origin and in the host country while underlining their interconnectedness. As regards impacts on places of destination, people often believe that these are negative-because they fear that newcomers take jobs, burden public services, create social tensions and even increase criminality. The evidence suggests that these popular concerns are exaggerated and often unfounded. Still, perceptions matter-and these warrant careful investigation to help frame the discussion of policy. The multiple impacts of movement in these different places are critical in shaping the overall human development effects of movement; this chapter addresses each in turn. At places of origin, impacts can be seen on income and consumption, education and health, and broader cultural and social processes. These impacts are mostly favourable, but the concern that communities lose out when people move needs to be explored. Our review of the evidence shows that impacts are complex, contextspecific and subject to change over time. The nature and extent of impacts depend on who moves, how they fare abroad and their proclivity to stay connected, which may find expression in flows of money, knowledge and ideas, and in the stated intention to return at some date in the future. Kerala in India and Fujian Province in China-impacts on local communities may be more pronounced than national impacts. Yet the flow of ideas can also have far-reaching effects on social norms and class structures, rippling out to the broader community over the longer term. Some of these impacts have traditionally been seen as negative, but a broader perspective suggests that a more nuanced view is appropriate. Much academic and media attention has been directed to the impacts of migrants on places of destination. We investigate the vast empirical literature on these issues, which reveals that these fears are exaggerated and often unfounded. Nevertheless, these perceptions matter because they affect the political climate in which policy decisions about the admission and treatment of migrants are made-fears may stoke the flames of a broader hostility to migrants and allow political extremists to gain power. Indeed, historical and contemporary evidence suggests that recessions are times when such hostility can come to the fore. We end this chapter by tackling the thorny issue of public opinion, which imposes constraints on the policy options explored in the final chapter. The exceptions- countries with significant shares abroad-are often small states, including Caribbean nations such as Antigua and Barbuda, Grenada, and Saint Kitts and Nevis. The higher the share, the more likely it is that impacts on people who stay will be more pervasive and more profound. In general, the largest impacts at places of origin are felt by the households with an absent migrant. However, the community, the region and even the nation as a whole may be affected. In return for supporting the move, the family can expect financial remittances when the migrant is established-transfers that typically far outweigh the initial outlay or what the mover might have hoped to earn in the place of origin.

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The decision of whether to release captive-reared animals into the wild after completion of a field research project demands more rigorous evaluation than for field-captured animals. Animals should be in good physical condition and released when weather conditions are favorable, at a time of day when they are able to locate food and cover that meet survival needs. However, if the animal was subject to a major invasive procedure, it may not be appropriate for additional experimentation. When animals must be euthanized, responsible methods appropriate for the species and circumstances must be used. Care must be taken to assure that the animal is dead before disposal of the carcass. Also, disposal procedures must prevent carcasses containing toxic substances or drugs from the research investigations or euthanasia procedures to enter the food web of other animals. To the extent feasible, euthanized animals should be properly preserved and used as voucher specimens or for teaching purposes. Safety Considerations Researchers working with free-ranging wildlife are subject to enhanced levels of exposure to wildlife diseases transmissible to humans. Consultation with a physician regarding immunization or other preventative treatment is advised when serious diseases for humans commonly occur in the populations being studied. Investigators who become ill should seek medical assistance and advise their physicians of their exposure to potentially hazardous animals, diseases, and environmental conditions. Acknowledgments these guidelines were prepared by a committee of the Wildlife Society appointed by J. Foreyt Literature Cited Ad Hoc Committee on Acceptable Field Methods in Mammalogy, 1987, Acceptable field methods in mammalogy: Preliminary guidelines approved by the American Society of Mammalogists: Journal of Mammalogy, v. Ad Hoc Committee on the Use of Wild Birds in Research, 1988, Guidelines for use of wild birds in research: Auk, v. Sources of assistance for technical information, implementation, and interpretation of the Animal Welfare Act Animal Welfare Information Center National Agricultural Library 10301 Baltimore Ave. Ad Hoc Committee on the Use of Wild Birds in Research, 1988, Guidelines for use of wild birds in research: Auk, vol. Guidelines for Proper Care and Use of Wildlife in Field Research 71 72 Field Manual of Wildlife Diseases: Birds Section 2 Bacterial Diseases Avian Cholera Tuberculosis Salmonellosis Chlamydiosis Mycoplasmosis Miscellaneous Bacterial Diseases Inoculating media for culture of bacteria Photo by Phillip J. Redman Introduction to Bacterial Diseases 73 Introduction to Bacterial Diseases "Consider the difference in size between some of the very tiniest and the very largest creatures on Earth. In addition to infection, some bacteria cause disease as a result of potent toxins that they produce. Bacteria of the genus Clostridium are responsible for more wild bird deaths than are other disease agents. The descriptive pathology is referred to as a necrotizing gastroenteritis or necrotic enteritis and the disease as clostridial enterotoxemia. Necrotic enteritis of wild waterbirds, especially geese, has been reported with increasing frequency during recent years. The high prevalence of avian tuberculosis infection that has occurred since 1982 in a free-living foster-parented Quote from: Garrett, L. Salmonellosis has become a major source of mortality at birdfeeders throughout the Nation, and mycoplasmosis in house finches has become the most rapidly spreading infectious disease ever seen in wild birds. This disease reached the Mississippi River and beyond within 2 years of the 1994 index cases in the Washington, D. As a group, bacterial diseases pose greater human health risks than viral diseases of wild birds. Of the diseases addressed in this section, chlamydiosis, or ornithosis, poses the greatest risk to humans. Numerous other diseases afflict wild birds, some of which are identified in the chapter on Miscellaneous Bacterial Diseases included at the end of this section. Timely and accurate identification of causes of mortality is needed to properly guide disease control operations. The magnitude of losses and the rapidity with which those losses can occur, as reflected in the chapters of this section, should be a strong incentive for those who are interested in the conservation of wild species to seek disease diagnostic evaluations when sick and dead birds are encountered. In order to accurately determine what diseases are present, specimens need to be sent to diagnostic laboratories that are familiar with the wide variety of possible diseases that may afflict wild birds. Those laboratories must also have the capability to isolate and identify the causative agents involved. Susceptibility to infection and the course of disease - whether or not it is acute or chronic - is dependent upon many factors including sex, age, genetic variation, immune status from previous exposure, concurrent infection, nutritional status, and other aspects of the host; strain virulence and other aspects of the bacterium; and dose and route of exposure.

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Estimates suggest that approximately 15,000 people are hospitalized and over 500 deaths occur each year from Salmonella infections. There are thousands of Salmonella serotypes, and many naturally inhabit avian, mammalian, and reptilian gastrointestinal tracts. Poultry is the main source of the salmonellae in the food supply; other vehicles for disease transmission include raw salads, milk, water, and shellfish. Infection with many Salmonella serotypes causes gastroenteritis with associated diarrhea, vomiting, febrile illness, headache, and dehydration. Septicemia, enteric fever, and localized infections may also evolve from salmonellosis infection. The most highly pathogenic of the salmonellae, S typhi, causes typhoid fever, which includes symptoms of septicemia, high fever, headache, and gastrointestinal illness. S typhimurium was the pathogen used in 1984 by an Oregon cult to cause illness by purposeful contamination of salad bars. A 1985 salmonellosis outbreak affecting more than 16,000 persons caused by cross-contamination of pasteurized with unpasteurized milk demonstrates the potential for large-scale illness caused by the salmonellae in the food distribution system. In 1981 Dr Willy Burgdorfer and colleagues first observed spirochetes in adult Ixodes scapularis (then called I dammini) ticks collected from vegetation on Shelter Island, New York, a known endemic focus of Lyme disease. The deer tick, I scapularis, is now known to be the primary vector of Lyme disease in the northeastern and north central United States (Figure 25-4). Other vectors are closely related ixodid ticks; including I pacificus in the western United States, I ricinus in Europe, and I persulcatus in Asia. Based on genotyping of bacterial isolates, B burgdorferi has now been subdivided into multiple Borrelia species or genospecies. This species, along with two others, B afzelii and B garinii, are found in Europe, although fig. Ixodes scapularis tick, also called the black-legged tick, is found on a wide range of hosts and is considered the main vector of the Lyme disease spirochete, Borrelia burgdorferi. I scapularis is also a vector of Anaplasma phagocytophilum and Babesia microtii, the causative agents of human granulocytic ehrlichiosis and babesiosis, respectively. Darkfield photomicrograph of the Lyme disease spirochete, Borrelia burgdorferi, magnified 400x. Photograph: Courtesy of Centers for Disease Control and Prevention Public Health Image Library. Early systemic manifestations can include malaise, fatigue, fever, headache, stiff neck, myalgia, migratory arthralgias, and lymphadenopathy, which may last for several weeks if untreated. In weeks to months after onset of erythema migrans, neurological abnormalities may develop, including facial palsy, chorea, cerebellar ataxia, motor or sensory radiculoneuritis, myelitis, and encephalitis; these symptoms fluctuate and may become chronic. Since then, the number of reported cases has increased steadily, with 17,029 cases reported in 2001. A newly recognized tick-transmitted disease that produces a rash (erythema migrans) very similar to, and often indistinguishable from, that seen in Lyme disease has been identified in the southeastern and south central United States. This finding led to speculation among physicians and researchers that a new tick-associated spirochete may be responsible. Relapsing fever caused by the spirochete B recurrentis can be transmitted by the body louse Pediculus humanus. B hermsii, the causative agent of tick-borne relapsing fever, is transmitted by the soft tick Ornithodoros hermsii. Although the total duration of louse-borne disease usually averages 13 to 16 days, the tick-borne disease often lasts longer. After a relapsing fever outbreak among five persons visiting a cabin in western Montana,94 spirochetes isolated from two of the patients were identified as B hermsii, and O hermsi ticks were collected from the cabin in which the patients had slept. This was the first report of both B hermsii and O hermsi in Montana, suggesting the risk of infection may be expanding beyond the previously recognized geographic range. Ehrlichiosis Human granulocytic ehrlichiosis is caused by infection with Anaplasma phagocytophilum, whereas the agent of human monocytotropic ehrlichiosis is Ehrlichia chaffeensis. Monocytotropic ehrlichiosis occurs in rural and suburban areas south of New Jersey to Kansas and in California, and granulocytic ehrlichiosis occurs in areas where Lyme disease is endemic.

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The virus is initially localized to coated pits, where it is engulfed in a coated vesicle and transported to the endosomal compartment within the interior of the cell. A decrease in the pH in the interior of the vesicle induces a conformational change in the glycoprotein spikes, and rearrangement of the E1 glycoprotein mediates fusion of the virion envelope with the endosomal membrane. These procedures are being used to develop improved vaccines,15 but they could also be used to enhance specific characteristics required for weaponization. Shown is the three-dimensional reconstruction of Sindbis virus at 28 Е resolution from computer-processed images taken by electron cryomicroscopy. Each spike protrudes 50 Е from the virion surface and is believed to be composed of three E1­E2 glycoprotein heterodimers. The space between the spikes and the nucleocapsid would be occupied by the lipid envelope. The green arrows mark visible points of interaction between the nucleocapsid and transmembranal tails of the glycoprotein spikes. Computer models: Courtesy of Angel M Parades, Cell Research Institute and Department of Microbiology, the University of Texas at Austin, Austin, Texas. The polymerase genes are followed by a second coding region of approximately 3,800 nucleotides, which contains the information that directs the synthesis of the viral structural proteins. After release of the C protein, the free amino terminus of E3 is bound to the membranes of the rough endoplasmic reticulum. As the synthesis of nascent E3 and E2 continues, the polypeptide is translocated into the lumen of the endoplasmic reticulum, where oligosaccharides and fatty acids are added. The 6 K polypeptide probably serves as an signal for membrane insertion of the second glycoprotein, E1, and is subsequently cleaved from both E2 and E1 by signal peptidase. The precursor pE2 is cleaved to the mature E2 and E3 glycoproteins soon after the glycoproteins leave the Golgi apparatus,92 and the mature viral spikes assume an orientation in the plasma membrane with the bulk of the E2 and E1 polypeptides exposed on the exterior surface of the cell. In vertebrate cells, final assembly of progeny virus particles happens by budding exclusively at the plasma membrane,93 and in arthropod cells, budding also occurs at intracellular membranes. Additional lateral associations between the individual spikes stabilize the lattice and promote additional E2­C protein interactions. The growing lattice may draw the membrane around the nucleocapsid, completing the process of envelopment with the release of the spherical virus particle. Maximal amounts of virus are typically produced from mammalian cells within 8 to 10 hours after infection, and disintegration of the infected cell is likely caused by programmed cell death (apoptosis) rather than direct effects of the virus on cellular function. The surviving cells continue to produce lesser amounts of virus, often for weeks or months. The ability of the virus to replicate without causing cell death in arthropod cells may be critical for maintenance of the virus in the mosquito vector in nature. Little is known of the pathogenesis even after natural vectorborne infections of humans, mainly because of limited autopsy material. Widespread hepatocellular degeneration and interstitial pneumonia, not ordinarily seen in experimentally infected animals, were frequent histological findings 250 in these cases of severe human disease. Mice uniformly exhibit a severe paralytic episode before death from diffuse encephalomyelitis following peripheral or aerosol administration of TrD or V3000. The specific mechanism of neuroinvasion in the case of peripheral inoculation of virus is not completely understood, yet animal studies have elucidated some important features. Virus may then invade olfactory neuron cell bodies or their axons and may be carried via the olfactory nerves into the olfactory bulbs of the brain. Surgical or chemical ablation of the olfactory lining in mice reportedly delayed neuroinvasion via the olfactory nerves. The understanding of the mechanism of neuroinvasion after respiratory infection is more clear. Although the olfactory bulb and olfactory tract were sites of early viral replication, the virus did not appear to spread to the rest of the brain along the neural tracts in these monkeys, as it does in mice. The mechanisms of neuroinvasion by peripheral versus aerosol administration are of significant practical concern because, as studies have shown, the immunological mechanisms of virus neutralization respective to each route can vary greatly. Neurons are the primary viral target in the brain and neuronal death by necrosis and/or apoptosis, accompanied by inflammatory changes, are the key consequences of infection.


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