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A double-door autoclave blood pressure pulse buy cheap indapamide 1.5mg, dunk tank one direction heart attack discount indapamide online, or fumigation chamber must be provided at the containment barrier for the passage of materials blood pressure chart images purchase generic indapamide canada, supplies arteria jejunalis discount indapamide 2.5mg overnight delivery, or equipment in or out of the laboratory. Sinks inside the suit laboratory should be placed near procedure areas and be connected to the wastewater decontamination system. Walls, foors, and ceilings of the laboratory must be constructed to form a sealed internal shell to facilitate fumigation and prohibit animal and insect intrusion. The internal surfaces of this shell must be resistant to chemicals used for cleaning and decontamination of the area. All penetrations in the internal shell of the laboratory, suit storage room and the inner change room must be sealed. The supply and exhaust components of the ventilation system must be designed to maintain the laboratory at negative pressure to surrounding areas and provide differential pressure or directional airfow as appropriate between adjacent areas within the laboratory. The exhaust air discharge must be located away from occupied spaces and air intakes. Biological validation must be performed annually or more often if required by institutional policy. Effuents from personal body showers and toilets may be discharged to the sanitary sewer without treatment. Autoclaves that open outside of the laboratory must be sealed to the interior wall. Positioning the bioseal so that the equipment can be accessed and maintained from outside the laboratory is strongly recommended. In both instances, the institutional management must provide facilities, staff, and established practices that reasonably ensure appropriate levels of environmental quality, safety, security and care for the laboratory animal. As a general principle, the biosafety level (facilities, practices, and operational requirements) recommended for working with infectious agents in vivo and in vitro are comparable. In the animal room, the activities of the animals themselves can present unique hazards not found in standard microbiological laboratories. Animals may generate aerosols, they may bite and scratch, and they may be infected with a zoonotic agent. The co-application of Biosafety Levels and the Animal Biosafety Levels are determined by a protocol-driven risk assessment. These recommendations presuppose that laboratory animal facilities, operational practices, and quality of animal care meet applicable standards and regulations. In addition, the organization must have an occupational health and safety program that addresses potential hazards associated with the conduct of laboratory animal research. Traffc fow that will minimize the risk of cross contamination should be incorporated into the facility design. The recommendations detailed below describe four combinations of practices, safety equipment, and facilities for experiments with animals involved in infectious disease research and other studies that may require containment. Investigators that are inexperienced in conducting these types of experiments should seek help in designing their experiments from individuals who are experienced in this special work. Facility standards and practices for invertebrate vectors and hosts are not specifcally addressed in this section. The reader is referred to Appendix E for more information on the Arthropod Containment Guidelines. Animal Biosafety Level 1 Animal Biosafety Level 1 is suitable for work in animals involving well-characterized agents that are not known to cause disease in immunocompetent adult humans, and present minimal potential hazard to personnel and the environment. Special containment equipment or facility design may be required as determined by appropriate risk assessment. Personnel are advised of potential hazards and are required to read and follow instructions on practices and procedures. The supervisor must ensure that animal care, laboratory and support personnel receive appropriate training regarding their duties, animal husbandry procedures, potential hazards, manipulations of infectious agents, necessary precautions to prevent exposures, and hazard/ exposure evaluation procedures (physical hazards, splashes, aerosolization, etc. Personnel must receive annual updates and additional training when procedures or policies change. Records are maintained for all hazard evaluations, employee training sessions and staff attendance. A sign incorporating safety information must be posted at the entrance to the areas where infectious materials and/or animals are housed or are manipulated. Security-sensitive agent information should be posted in accordance with the institutional policy. Only those persons required for program or support purposes are authorized to enter the facility. All persons including facility personnel, service workers, and visitors are advised of the potential hazards (natural or research pathogens, allergens, etc. Gloves are worn to prevent skin contact with contaminated, infectious and hazardous materials, and when handling animals. Gloves and personal protective equipment should be removed in a manner that minimizes transfer of infectious materials outside of the areas where infectious materials and/or animals are housed or are manipulated. Eye and face and respiratory protection should be used in rooms containing infected animals, as dictated by the risk assessment. Food must be stored outside of the laboratory in cabinets or refrigerators designed and used for this purpose. All procedures are carefully performed to minimize the creation of aerosols or splatters of infectious materials and waste. Used disposable needles must be carefully placed in puncture-resistant containers used for sharps disposal. Non-disposable sharps must be placed in a hard-walled container for transport to a processing area for decontamination, preferably by autoclaving. Animals and plants not associated with the work being performed must not be permitted in the areas where infectious materials and/ or animals are housed or are manipulated. All wastes from the animal room (including animal tissues, carcasses, and bedding) are transported from the animal room in leak-proof, covered containers for appropriate disposal in compliance with applicable institutional, local and state requirements. Special containment devices or equipment may not be required as determined by appropriate risk assessment. Protective laboratory coats, gowns, or uniforms may be required to prevent contamination of personal clothing. Protective outer clothing is not worn outside areas where infectious materials and/or animals are housed or manipulated. Protective eyewear is worn when conducting procedures that have the potential to create splashes of microorganisms or other hazardous materials. Persons who wear contact lenses should also wear eye protection when entering areas with potentially high concentrations or airborne particulates. Gloves and personal protective equipment should be removed in a manner that prevents transfer of infectious materials. The animal facility is designed, constructed, and maintained to facilitate cleaning and housekeeping. It is recommended that penetrations in foors, walls and ceiling surfaces be sealed, including openings around ducts, doors and doorframes, to facilitate pest control and proper cleaning. Cabinets and bench tops must be impervious to water and resistant to heat, organic solvents, acids, alkalis, and other chemicals. External windows are not recommended; if present windows must be resistant to breakage. Ventilation should be provided in accordance with the Guide for Care and Use of Laboratory Animals. Internal facility appurtenances, such as light fxtures, air ducts, and utility pipes, are arranged to minimize horizontal surface areas to facilitate cleaning and minimize the accumulation of debris or fomites. If foor drains are provided, the traps are flled with water, and/or appropriate disinfectant to prevent the migration of vermin and gases. The mechanical cage washer should have a fnal rinse temperature of at least 180?F. If manual cage washing is utilized, ensure that appropriate disinfectants are selected. It also addresses hazards from ingestion as well as from percutaneous and mucous membrane exposure. Appropriate personal protective equipment must be utilized to reduce exposure to infectious agents, animals, and contaminated equipment.

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Results: In multivariate analysis blood pressure medication algorithm purchase indapamide 1.5mg fast delivery, older patients with aggressive histologies were 1 arteria 90 entupida best order for indapamide. Studies addressing supportive care blood pressure solutions discount 1.5 mg indapamide fast delivery, particularly to blood pressure chart canada generic indapamide 1.5mg on line older patients who are most likely to benefit from this approach, are recommended. Allogeneic transplants in follicular lymphoma: higher risk of disease progression after reduced? Second autologous stem cell transplantation for relapsed lymphoma after a prior autologous transplant. Results: Factors adversely associated with overall survival included increasing age, decreased performance sta? Despite the rituximab group containing older and more heavily treated patients, progression? In multivariate analysis, pretransplant rituximab, age <55, and fewer than 3 lines of chemotherapy were all asso? Excluded were patients with planned second transplants, patients younger than 21 and cord blood transplants. Results: In both groups, recipient aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. Patients and Methods: 166 patients who received second transplants between 1986 and 2004 were analyzed. Corresponding probabilities in patients with lower performance scores were 33% and 61%. Conclusions: Second transplants are effective for patients with good performance status who suffer late sec? Results: Graft failure rates were higher after cyclophosphamide (Cy) conditioning; the highest rate (60%) seen in patients who received? When comparing Bu+Cy and Cy alone in these heavily transfused patients, use of Bu+Cy ap? Results: Patients >40 years comprised a significantly higher proportion of patients who had: received >50 transfusions, had prior exposure to immunosuppressive therapy, poor performance scores, a longer time to transplant and received grafts from peripheral blood. Conclusions: these data suggest interesting results in spite of low rates of sustained donor engraftment mainly for those patients receiving a lower nucleated cell dose. Cox regression models were constructed to identify risk factors that influence outcome after transplantation. Results: the only risk factor that predicted leukemia recurrence and overall and leukemia? Conclusions: Children who underwent transplantation in remission had superior outcomes compared with children who underwent transplantation during relapse or persistent disease. Results: Cumulative incidence of relapse/progression was significantly lower and progression? However, neither system was strongly predictive of outcomes indicating the need for newer schemes incorporating other prognostic markers. Patients and Methods: Retrospective analysis of 3,578 patients identified 36 (1%) with IgD and 11 (0. Results: B*44 was observed less frequently among the patients (a protective effect) frequency (f): 0. Also further analysis on the role of homozygosity, age, ethnical origin and allele frequencies are pending. Conclusions: Second transplant is feasible, however it has a high early mortality and a small minority of patients remains alive disease? Further efforts are needed to try to identify groups that might benefit from such therapy or to see if earlier identification and treatment can change this natural history. After comparing outcomes, we looked for dose effects and identified low and high dose smoking groups (>10 pack years, >1 pack per day). Physicians can use these data to counsel patients who smoke about transplant risk. A prospective study with detailed demographic, pulmonary function test and quality of life data would improve our understanding of this issue. Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma. Draft data collection forms were prepared in 2008 and a Cellular Therapies Working Committee was formed. All rights conferred by virtue of the International Copyright Convention are specifcally reserved to the Council of Europe and any reproduction or translation requires the written consent of the Publisher. The reason is that the cells contained in the umbilical cord blood have therapeuthe cells contained in the tic value for the treatment of malignant umbilical cord blood have and non-malignant blood disorders and therapeutic value for immune diseases. Cord blood has been the treatment of blood used in transplant medicine since the disorders and immune frst allogeneic cord blood transplant diseases. Allogeneic cord blood transplantation in children has similar survival rates compared to transplantation of haematopoietic stem cells from other sources. In recent years, the number of cord blood banks ofering families to store the cord blood of their babies for possible future private uses against up front and yearly fees has grown. This guide has been prepared by the Council of Europe European Committee on Organ Transplantation, composed of internationally recognised experts, to provide clear, accurate and balanced information about the use of cord blood in medical treatment and to guide parents through their blood storage options. Afer a baby is born and the umbilical cord is cut, some blood remains in the blood vessels of the placenta and the portion of the umbilical cord that remains attached to it. Afer birth, the baby no longer needs this extra blood which is called umbilical cord blood or cord blood for short. Cord blood contains all the normal elements of blood red blood cells, white blood cells, platelets and plasma. But it is also rich in haematopoietic stem cells, similar to those found in the bone marrow. Stem cells have the remarkable potential to develop into many diferent cell types in the body during early life and growth. They serve as a sort of internal repair system, dividing more or less without limit to replenish other cells as long as the person is still alive. Haematopoietic stem cells are the blood cells that give rise to all the other blood cells. Red blood cells, which transport blood that remains in oxygen throughout the body; the umbilical cord connected to the placenta after childbirth. Every year, thousands of patients are diagnosed with malignant or non-malignant haematological diseases that can be treated using haematopoietic stem cell transplantation as part of the therapeutic regime. The blood from the umbilical cord and the placenta is then the blood from the no longer needed by the baby or the umbilical cord and the mother. At this point, the cord blood can placenta is no longer needed by the baby or be collected, either before or afer the the mother after birth. If the cord blood is not collected for storage purposes, it will be thrown away and incinerated like other 6 did you know? In order to collect enough cells that can be used for transplantation it is important to collect an adequate volume of cord blood (some countries recommend at least 70 ml). Many collected cord blood units however, end up not being stored for transplantation because they do not contain enough blood or cells to be transplanted into a patient. When the cord blood unit is considered to be suitable for transplantation, it is given an identifcation number and frozen for long-term storage in the bank. Normally, cord blood units are stored in liquid nitrogen or in the vapour phase of liquid nitrogen to keep them at -150 C or lower. Once collected and stored in a public bank, the cord blood unit is listed in a registry and made available for patients. Transplantation of haematopoietic stem cells is currently the only available treatment for patients with blood and immune system disorders such as Haematopoietic stem cells myelomas, leukaemia, lymphomas and used for transplantation myeloproliferative syndrome. Doctors will then use haematopoietic stem cells to repopulate their bone marrow with healthy cells. Haematopoietic stem cells used for transplantation may be obtained from diferent sources: This has been the main source of haematopoietic stem cells for the last few decades.

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A traceable standard is one that can be directly linked to pulse pressure 62 generic indapamide 2.5 mg otc a provider that has documented the accuracy of the measuring device heart attack quizzes order indapamide overnight delivery. Other vendors may provide similar products but they must have a direct link to blood pressure extremely low buy indapamide 2.5 mg mastercard records indicating accuracy to blood pressure ranges pregnancy order indapamide in india a known standard. An alternative to using the actual traceable standard is to calibrate a similar device against the traceable standard and use the newly qualified device for routine measurements. If a traceable standard cannot be obtained, then the Processing Facility must document how they determined the measurement reading to be accurate. Explanation: When equipment is found to be out of calibration or specification, the validity of previous measurements and decisions based on those measurements should be reviewed. There should be documentation that the cellular therapy products manufactured during this period of uncertainty have been evaluated and determined to be conforming to specification or corrective action has been documented. This should include an investigation of potential adverse events to manufactured products using the equipment tracking system. Explanation: There must also be a complete record of lot numbers and expiration dates for reagents and disposables used for the procedure. Likewise, the identity of the key equipment used during processing must also be documented. It is critical to be able to link reagents, supplies, and equipment to the processing of each cellular therapy product in the case of an adverse event or recall of reagents, supplies, and/or equipment. Implementation of a carefully planned inventory control system helps to facilitate documentation of lot numbers; prevention of the use of outdated or quarantined supplies; and linkage of products processed to reagents, supplies, and equipment in a timely manner. Evidence: Processing chart records are required to contain a listing of the required reagent and supply lots and the equipment used. Explanation: Critical materials must be defined by the Processing Facility and tracked under its materials management system. Processing records for each cellular therapy product must include the identity of all critical supplies and reagents used in the procedure. This is generally tracked by including a listing of the name of the item, manufacturer, lot number, and expiration date (where available) of the material in the processing record. The materials management system must also allow tracing of all products manufactured using a given lot of reagent or supply. There are a variety of ways this can be accomplished, so long as the information can be easily obtained. A method to do this might include selecting a lot number of a reagent from the critical supplies and inventory list and asking for manufacturing records from products that are in inventory or have been released. Ordering and stocking procedures to limit the number of different lots of reagents and supplies in the Processing Facility at a given time may be part of an inventory control program. In some settings, such as where multiple additives are used, the additional information is part of the accompanying documentation, especially where label space is limited. The standard terminology is structured in a manner that allows revisions, additions, and deletions as necessary on a continuous basis. Inspectors should review Chapter Three, Cellular Therapy, in this document before conducting an inspection. It would be helpful to have the document available for reference during the inspection as well. Such standardization is even beneficial to, and thus required for, autologous cellular therapy products. Explanation: the printing of labels can either be done by pre-printing sets of labels to be used during processing or by printing them on demand. On-site, the inspector should verify that the labels submitted are in fact the labels in use at the Processing Facility. The inspector should focus more time on other aspects of the labeling process, specifically assessment of its adequacy to confirm proper identification of products and product samples. Stocks of unused labels for different products must be stored separately to prevent errors. Labels should be organized physically or electronically so staff can readily identify the labels and be able to distinguish labels of different products from one another. Inspection must include comparison with a label approved by the Processing Facility Director or designee. The process and outcome must be documented prior to release of the labels from the quarantine area. It is recommended that the inspection of labels at receipt or after printing be performed by one person and independently verified by a second person. If bar code scanning technology is used, verification of appropriate scanning of the label should be included in this comparison before release. Example(s): A log(s) or form(s) is often used to document receipt, quarantine, inspection against a master label book of pre-printed labels or label templates and evidence of accurate bar code scanning, as well as release for use or rejection pending disposal. The system used to generate such labels must be validated to confirm that each label type is in compliance with the template approved by the Processing Facility Director or designee. The validation of automatic label generation, including test cases and associated documentation and software-defined tables, should be reviewed by the inspector and provides evidence of the mechanisms used by the software to control and verify label content, including the use of bar-coded information. Validation of software-controlled labeling systems used to create or modify labels should be documented in a validation plan at the site. Explanation: the document control system used for these various elements and what constitutes a label version must be defined by the Processing Facility. The version number may or may not appear on the label, as defined by labeling process at each facility. Only the current version of each label should be available for use in the processing area. A process for controlled rotation of labels should be evident for inventoried labels. Evidence: the label version control should be reviewed by the inspector to confirm that the intended labels are generated. For label changes, there should be a process for controlled versioning and implementation of changes in manual or automated systems, including archived label examples or templates and reconciliation of available and inventoried labels, as applicable to the labeling systems in use. Example(s): Changes in the requirement for a uniform product proper name or changes in the wording of required statements or warning statements would require a version change to that label or label element. Log(s), form(s) and/or software validation documentation specific to a particular archived label should show label versions linked to specific dates of use. Explanation: this standard requires facilities to have a careful process for electronically transmitting information (such as with a bar code) and to double check the information rather than becoming solely dependent on the technology to work correctly. Explanation: the inspector should examine labeled products on-site to verify that labels are firmly attached or affixed and that sufficient area of the product remains uncovered to allow examination of contents. Explanation: When Processing Facilities print labels on demand, the manner in which the database is being generated needs to be validated. For automatic labeling systems using computer-assisted label verification of parts of the label, electronic verification must be part of the label system validation. No fewer than two people must confirm that manually entered information on the label is accurate. One person may verify information if a validated process, such as computer checks or barcoding, is used. When transferring a cellular therapy product, labeling of new containers or samples shall meet the labeling requirements of the Standards, including documentation of verification of correct labeling information, whether by manual or automated methods. If information is not required, the data field should be marked not applicable or shall not appear. Explanation: Indelible ink must be used to record any information entered manually on the label. To support label integrity, computer-assisted labeling should include a check to confirm label stock is appropriately aligned in the printer and ink is smear-proof. Labels must have been validated to assure they remain legible under the conditions in which they are used. This is of particular importance for labels used on cryopreserved products and after thawing of the product in a water bath. Processing Facilities must use materials that meet criteria, if any, established by applicable regulatory authorities. Explanation: the product identifier must be unique for each donation event so that all parts of the donation and samples collected are labeled with the same product identifier.

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Phosphide interacts with moisture in the air between the grains to arrhythmia yawning generic 1.5mg indapamide otc liberate phosphine arrhythmia associates of south texas 1.5 mg indapamide free shipping. Phosphine is available in cylinders blood pressure zoladex discount 2.5 mg indapamide free shipping, either alone or combined with carbon dioxide arteria pharyngea ascendens cheap indapamide 1.5 mg fast delivery. Clinical effects Phosphine poisoning may occur following inhalation of phosphine or the ingestion of a phosphide. Inhalation causes irritation to the mucous membranes of the nose, mouth, throat and respiratory tract; chest tightness, breathlessness, chest pain, palpitations, and severe retrosternal pain are common. Nausea, vomiting, epigastric pain and diarrhoea may be so striking that a diagnosis of acute gastroenteritis is made. Consciousness is usually only mildly depressed; headache, dizziness and staggering gait may ensue. In more severe cases acute heart failure, pulmonary oedema (sometimes non-cardiogenic) and ventricular arrhythmias have been observed, particularly in children; cardiogenic shock results in metabolic acidosis, hyperlactataemia and acute renal failure. Other less common features include disseminated intravascular coagulation and hepatic necrosis. Clinical effects Severity increases with dose and duration of exposure; and although tissue damage begins immediately on exposure, some clinical effects may be delayed and evolve over hours or days. Skin exposure produces skin blisters and skin necrosis; erythema develops within a few hours of exposure; vesication usually begins on the second day after exposure and may progress for up to two weeks; necrosis of the epidermis and superfcial dermis is complete four to six days after exposure and separation of necrotic slough then begins; scab formation begins within seven days; by 16 to 20 days, separation of slough is complete and reepithelialization begins. Sulphur mustard depresses bone marrow function which may lead to secondary infection. Many different organisms could, in theory, be used deliberately and be distributed through food, water, or the air (by an explosive device, aerosol canister, or crop duster). This manual focuses on organisms that could be aerosolised and/or would cause serious or fatal infections. Recognition of release incidents Intentional and naturally occurring outbreaks may be indistinguishable initially. Symptoms of some forms of intentional or accidental chemical poisoning may mimic some infections (eg arsenic-contaminated coffee, Maine, 2003, and nicotine-contaminated minced meat, Michigan, 2003, both initially thought to be gastroenteritis; thallium poisoning, Florida, 1988, initially thought to be botulism). The tables below show the differential diagnoses for some important syndromic presentations. Telephone the microbiology laboratory in advance to tell them to expect the specimens and the risk / differential diagnosis. Label all specimens and forms as high risk or danger of infection (or otherwise identify them as high risk using locally agreed method). If possible, take specimens for bacterial culture before starting antibiotic treatment. Take at least four sets of blood cultures (two sets from each of two venepunctures at different sites at least 1 hour apart). Put each specimen in a separate plastic specimen bag (ie three specimens, three specimen bags); seal specimen bags, with tape if necessary: do not use clips, staples or pins this endangers the laboratory staff who open the bags. Fill in all request forms fully and accurately, giving the working diagnosis and as much clinical information about the case as you can (? Never put a request form in the same bag as a specimen use separate bags, then tape the bag containing the specimen and the bag containing the request form together (or use standard laboratory specimen bags with a separate compartment for the request form). Transport specimens to the local microbiology laboratory as soon as possible, using locally agreed procedures for high risk samples. Do not use vacuum-tube specimen transport systems Specimen packaging, labelling and transportation must comply with current national and international standards. For some toxins and organisms, such as botulinum toxin or smallpox, it may involve early administration of an immunoglobulin or vaccine. The decision to offer postexposure prophylaxis after a deliberate or accidental release should be taken after a risk assessment has been made of the likelihood and extent of exposure. Groups likely to need prophylaxis include persons exposed at the incident scene (including frst responders and handlers of contaminated clothing) and, for smallpox and pneumonic plague, contacts of cases, laboratory workers and others. The table below shows the drug/s of frst choice and alternatives (for use when the drug of frst choice is contraindicated or is not available) in order of preference. It also includes alternatives for use when the organism is known to be sensitive to the drug (eg amoxicillin for anthrax): these alternatives, when appropriate, may be particularly useful for small children, pregnant women and babies. Except where specifed, antibiotic prophylaxis should begin, if possible, within 24 hours of exposure. These provide for initial (up to frst 10 days) post exposure prophylaxis with ciprofoxacin and for completion of treatment with either doxycycline or ciprofoxacin. Ciprofoxacin is licensed for use in children over 1 year of age for the prophylaxis and treatment of anthrax but not in pregnant women. There have been no formal studies of the use of ciprofoxacin in pregnancy, but it is unlikely to be associated with a high risk of abnormalities of foetal development. Ciprofoxacin does not enter breast milk in suffcient amounts to be harmful but the manufacturer advises avoidance. Systematic review of the use of fuoroquinolones in children suggests that the risk of arthropathy is relatively low and reversible with appropriate management. The risk of adverse effects of ciprofoxacin must be weighed against the risk of developing an infectious disease with signifcant morbidity and mortality. Doxycycline has adverse effects in children (deposition in growing bones and teeth, causing staining and, occasionally, dental hypoplasia), but may be used in a short course to initiate chemoprophylaxis, if ciprofoxacin and amoxicillin / co-amoxiclav are all contraindicated, until the most appropriate alternative antibiotic has been determined by sensitivity testing of the release strain. Doxycycline should not be given to breast feeding mothers; or if there is no alternative, breast feeding should be discontinued while treatment is given. For patient information sheets, patient group directions, and additional information on ciprofoxacin and doxycycline, go to: Antibiotic occupational 100mg orally bd 1g per day) or prophylaxis may risk assessment. Naturally acquired human anthrax is usually the result of contact with an infected animal, carcass or animal product. Clinical features depend on route of exposure: contact with abraded skin causes cutaneous anthrax; breathing in the spores causes inhalational anthrax; eating undercooked anthraxcontaminated meat causes gastrointestinal anthrax. Occupational risks: working with animals or animal hides, skins or hair, as in Hawick, Scotland in 2006 where there was one death, or working with the organism in the laboratory. Other risks: threatening letters or suspicious packages; contaminated heroin has been described as a source of necrotic injection-site infection and severe sepsis (Scotland / England / Germany 2009-2012). Incubation period usually one to seven days (range < 24 hours to 60 days post exposure). Botulinum toxin has seven antigenically distinct forms, A-G (A and B most common in natural human disease), toxin acts by blocking acetylcholine release at the neuromuscular junction. Toxin is amongst the most lethal known, but is inactivated by normal cooking of food and by chlorination of water. Botulism follows absorption of toxin into bloodstream after eating toxin-containing food, or following local production of toxin by C botulinum in a wound (or, in infant botulism, intestine), or breathing in pure toxin. Inhalation botulism does not occur naturally but could follow the deliberate release of aerosolised toxin. Speed of onset and severity of illness are related to dose and route of exposure: six hours to eight days after ingestion of toxin: onset might be more rapid after inhalation. Zoonotic; affecting cows (Brucella abortus), sheep, goats and camels (B melitensis), pigs (B suis), and other mammals. Naturally acquired human infection follows drinking unpasteurised milk or eating unpasteurised milk products from infected animals; breathing in the organism or directly contaminating the eyes, nose, mouth or abraded skin during close contact with infected animals, products of conception, or carcasses, or while working with the organism in the laboratory, and the accidental inoculation of live attenuated animal vaccine. B melitensis, B abortus and B suis cause similar human illnesses (B melitensis causes the most severe disease); clinical features do not depend on route of exposure. Occupational risks for: animal handlers, vets, meat packers and abattoir workers exposed to infected animals, carcasses, or contaminated dust (eg when washing down buildings); laboratory workers. Naturally acquired human disease is the result of close contact with an infected animal or carcass, or a laboratory exposure; there is no environmental reservoir infection acquired by direct contact of organism with cut or abraded skin, or eyes, nose or mouth, or by inhalation. Occupational risks: work with organism in laboratory; in endemic areas, risk for stablehands, muleteers, vets and abattoir workers exposed to infected animals or carcasses. Naturally acquired human disease usually the result of a bite from an infected fea. Clinical features depend on route of exposure: bite of infected fea causes bubonic plague; breathing in organism causes pneumonic plague; direct inoculation of Y pestis into bloodstream, or progression of bubonic or pneumonic plague cause septicaemic plague. Person to person spread of pneumonic (but not bubonic or septicaemic) plague can occur. Zoonotic: worldwide distribution, with reservoirs in sheep, cattle, goats, and other mammals infected animals usually asymptomatic but shed the organism in large numbers in placental tissue, amniotic fuid, milk, urine and faeces. Naturally acquired human infections usually caused by breathing in organism (eg when birthing infected animal, from contaminated dust, from aerosols in laboratory work); rarely, from eating or drinking unpasteurised milk or unpasteurised milk products.

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