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Outbreak control measures are directed either at the outbreak source purchase 10 mg glucotrol xl with amex can diabetes insipidus kill you, at disease vectors or their reservoirs buy glucotrol xl amex diabetes insipidus risk factors, or at protecting susceptible humans order glucotrol xl 10 mg mastercard diabetic diet exchange list. Communication should ideally be planned in advance, as part of overall outbreak preparation, with the development and implementation of a basic communication plan. The plan should address communication within the outbreak team, with the public and media, with government agencies such as the Ministry of Health, and with other agencies such as the Ministry for Primary Industries and, local authorities, industry groups and health service providers. Outbreak documentation and reporting helps to ensure that maximum benefit can be accrued from lessons learnt from outbreak response activities. The three phases of outbreak documentation on EpiSurv are as follows: recording the early details of the outbreak, recording the immediate outcome of the outbreak response and the final report summary of the methods and results. Notifiable disease surveillance activities in New Zealand are carried out by both local and national authorities. Key data fields collected include case demographics, clinical features and risk factors. EpiSurv also incorporates an outbreak functionality that enables cases to be linked via a common cause. EpiSurv7, a new web-based real-time version of the national notifiable disease surveillance system, was deployed in April 2007. National Guidelines 17 deployed a prototype contact-tracing module for use with EpiSurv7 for Exercise Cruickshank. The results can be appended to the appropriate case record and viewed as required. Analytic Component of an investigation designed to examine associations, commonly epidemiological putative or hypothesised causal relationships. Analytic epidemiological investigation* investigation is usually concerned with identifying or measuring the effects of risk factors, or is concerned with the health effects of specific exposure(s). Common types of analytic epidemiological investigation are case-control and cohort study designs. Carrier** A person or animal that harbours a specific infectious agent without discernible clinical disease and serves as a potential source of infection. Case-case study A study that compares the frequency of exposures among cases (ill people) with the frequency of exposures among other cases with a different strain of the same disease (ill people). Case-control study A study that compares the frequency of exposures among cases (ill people) with the frequency of exposures among controls (people without the illness). Cohort study A study that compares the rate of illness among people who have had a specific exposure with that among people who have not had that exposure. Common event An outbreak due to exposure of a group of persons to a noxious influence that outbreak is common to the individuals in the group, where the exposure is brief and essentially simultaneous and all resultant cases develop within one incubation period of the disease. Cases therefore have exposures that are grouped in place and time (synonym: point source outbreak). Common site An outbreak due to exposure of a group of persons to a noxious influence that outbreak is common to the individuals in the group, where exposures have occurred at the same place (or site) but over a longer time-period than those of common event outbreaks (i. In the Outbreak Report Form, these outbreaks are called common source in a specific place. Common source Outbreak due to exposure of a group of persons in a community to a noxious outbreak* influence that is common to the individuals in the group. Under this definition, all outbreaks except community-wide outbreaks would be described as common source. This document therefore subcategorises these outbreaks into common event outbreaks (where exposures are grouped in time and place), dispersed common source outbreaks (grouped in time but not in place) and common site outbreaks (grouped in place but not in time). Communicable An illness due to a specific infectious agent or its toxic products that arises disease** through transmission of that agent or its products from an infected person, animal or inanimate source to a susceptible host, either directly or indirectly through an intermediate plant or animal host, vector or inanimate environment (synonym: infectious disease). Community-wide An outbreak affecting individuals in a community, where transmission outbreak predominantly occurs by direct exposure of susceptible people to infectious people (synonym: person-to-person outbreak). Contact** A person or animal that has been in an association with an infected person or animal or a contaminated environment in such a way that provides an opportunity to acquire the infection. Contamination** The presence of a disease agent on a body surface, in clothes, bedding, toys or other inanimate articles or substances, including water and food. Dispersed common Outbreak due to exposure of a group of persons in the community to a noxious source outbreak influence that is common to the individuals in the group, where the exposures are not grouped in place (and may or may not be grouped in time). These outbreaks are often due to a distributed vehicle of infection transmission, such as a commercially prepared food item or a water supply. Environmental An examination of the surroundings external to human hosts of illness, with investigation (of the aim of identifying actual or potential vehicles of transmission and how outbreaks) processes in place failed to prevent human exposure to disease. Epidemic* The occurrence in a community or region of cases of an illness, specific health- related behaviour, or other health-related events clearly in excess of normal expectancy. Exposure* Proximity and/or contact with a potential source of a disease agent in such a manner that effective transmission of the agent, and harmful or protective effects of the agent may occur. Incubation period** The time interval between initial contact with an infectious agent and the first appearance of symptoms associated with the infection. In practice, symptoms used for calculation of the incubation period should reflect the case definition. Index case* The first case in a family or other defined group to come to the attention of the investigator. Institutional outbreak Outbreak confined to the population of a specific residential or other institutional setting, such as a hospital, rest home, prison or boarding school. Laboratory Comparison of infectious disease agents in samples taken from different investigation (of human hosts or vehicles of infection, with the aim of identifying vehicles for outbreaks) infection and delineating groups of individuals exposed to a common outbreak source. Nosocomial An infection occurring in a patient in a hospital or other health care facility in infection** whom it was not present or incubating at the time of admission. Outbreak* An epidemic limited to a localised increase in the incidence of a disease, such as in a village, town or closed institution. Outbreak description Component of outbreak investigation designed to describe the features of existing cases only (contrast with analytic epidemiologic study). Outbreak All activities undertaken to investigate and respond to outbreaks (includes management outbreak identification and preparation for investigation and response). Outbreak response Activities undertaken to prevent further transmission of disease, communicate effectively and to document the outbreak. Pathogenicity** The property of an infectious agent that determines the extent to which overt disease is produced in an infected population, or the power of the organism to produce disease. Primary case* The individual who introduces the disease into the group under study. Reservoir of Any person, animal, arthropod, plant, soil or substance (or combination of infection** these) in which an infectious agent normally lives and multiplies, on which it depends primarily for survival, and where it reproduces itself in such a manner that it can be transmitted to a susceptible host. Secondary case* Case of disease occurring among contacts within the incubation period, following exposure to the primary case. Source of illness** The person, animal, objects or substance from which a disease agent passes to a host. Susceptible** A person or animal not possessing sufficient resistance against a particular pathogenic agent to prevent contracting infection or disease when exposed to the agent.

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This guidance advises biologics) are newer drugs that have doctors on which drugs should be tried been developed in recent years as a frst cheap 10mg glucotrol xl amex diabetes diet calculator, in what situations glucotrol xl 10mg with visa diabetes with ophthalmic manifestations, and when diferent result of research into the processes in treatments should be ofered instead discount glucotrol xl 10 mg diabetes type 2 genetic factors. Or it can be given as weekly injections under the skin (subcutaneous injections) which you can learn to do for yourself. Rituximab • targets molecules on the surface of B-cells (cells that produce (Mabthera): antibodies, including rheumatoid factors) • is given as two infusions to begin with, usually two weeks apart – can then be repeated when symptoms return, which can be anything from six months to three years • is generally used for people who haven’t benefted from other treatments. If you develop chickenpox Certolizumab pegol; Etanercept; or shingles, or come into contact with Golimumab; Infiximab; Rituximab; someone who has chickenpox or shingles, Tocilizumab. This may include regular although most people will have only blood and/or urine tests. The use of these drugs • headaches is monitored, and if they’re given in • dizziness. This may include the • wheeziness Pneumovax vaccine, which protects 21 Alert card – Biological Therapy If you’re prescribed a biological therapy, we recommend you carry a biological therapy alert card, which you can get from your doctor or rheumatology nurse, or at www. If you become unwell, anyone treating you will know that you’re on biological therapy and are therefore at risk of its side- efects, including infections. It had a very powerful efect on infammation, and we now have man- Live vaccines such as yellow fever aren’t made steroids that can help to control recommended, although a live vaccine the symptoms of rheumatoid arthritis. Steroids Steroids (sometimes known by their full name, corticosteroids) aren’t the same as the steroids used by athletes to build up their body (anabolic steroids). Some steroids, like cortisone, are hormones that are produced naturally by the body. Cortisone was frst used 23 A physiotherapist can suggest exercises to help ease your • cataracts symptoms and • a rise in blood sugar or blood pressure stretch your joints. Doses of steroid tablets are kept as low as possible to keep the risk of side- efects to a minimum. Your doctor may also advise that you take calcium and vitamin D supplements or drugs called bisphosphonates alongside the steroids to help protect your bones Steroids can be given: against osteoporosis. It can be dangerous (intramuscular) or vein (intravenous) – to stop steroids suddenly. Exercise is an important part of this, • interference with the menstrual cycle and a physiotherapist can suggest • changes in mood, although this is more diferent exercises that may help ease common in people with a history of your symptoms, strengthen muscles mood disturbances. They can Steroid tablets tend to have more side- also teach you about joint protection efects, particularly when they’re used and can refer you to other healthcare in high doses. They can advise • weight gain you on how to reduce pain when you’re standing or walking and can suggest • thinning of the bones (osteoporosis) suitable footwear for both daily life • muscle weakness and sport. Physiotherapy and arthritis; Splints for The occupational therapist will watch the arthritis of the wrist and hand. They can also give Surgery is occasionally needed for you information on splints if you need rheumatoid arthritis. Hydrotherapy Badly damaged joints can be replaced involves doing special exercises in with man-made (artifcial) joints, which a warm-water pool. It can help reduce will greatly reduce pain and help to the pain in your joints, improve joint restore the function of the joint. Hip, mobility and strengthen your muscles, knee, shoulder and elbow replacements and you may also fnd it soothing are highly successful. You can ask your doctor or physiotherapist if they think hydrotherapy would be suitable for you. But overdoing it on Hand and wrist surgery; Hip replacement the good days can cause a fare-up the surgery; Knee replacement surgery; next day. Make it clear to your family and friends that not all days are the Self-help and daily living same. It’s important they realise that activities you enjoy on a good day may be The symptoms of rheumatoid arthritis impossible on a bad one. The efects of any condition can be Sometimes fare-ups have an obvious mental as well as physical, and people cause, such as another illness or stress, with rheumatoid arthritis are more likely but usually there’s no obvious trigger. How you feel This unpredictability is frustrating and mentally can also afect how you feel makes it difcult to plan ahead. Don’t be embarrassed to talk about this with your doctor if you’re feeling low – managing how you feel is as important as managing the physical symptoms. There are also support groups available if you want to meet other people who have rheumatoid arthritis, and you might fnd that information on pain management helps you to stay positive. Managing a fare-up Over time, you may get better at noticing the early signs of a fare-up. Sometimes a few days rest are all you need, though it’s important to do gentle exercise to help ease stifness. Some of the following tips will also help you to cope with a fare-up and to manage your symptoms in general. Figure 6 Recommended exercises for If you’re having regular fare-ups, people with rheumatoid arthritis you should mention this to your doctor. Recommended Not recommended It may be that you need to review Low-impact sports: Contact sports: your treatment. Rest will make infamed joints feel more comfortable, but without Swimming is a particularly good way movement your joints will stifen and of exercising for people with rheumatoid muscles will become weaker. It exercises the whole body to exercise the muscles without even but puts minimal strain on your joints moving the joint by doing isometric because the water supports your exercises. Contact sports and vigorous in static positions so the joint angle types of exercise should be avoided. Whichever sport or exercise you do, make Many yoga positions are isometric sure you warm up properly. A physiotherapist may be able If you go to a gym or health club, tell the to suggest some of this type of exercise. Your physiotherapist can advise Exercise is good for your general health, you about this too. Good shoes with shock-absorbing If a particular activity causes one or soles are essential. A podiatrist will be more of your joints to become warm able to advise you on suitable footwear and swollen, or if it causes severe pain, if necessary. Because of the way the joints work, the force put through your knees when you walk, run or go up and down stairs can be up to fve or six times your body weight, so keeping your weight down will help reduce the strain on your joints. Diet and nutrition Occasionally some people with arthritis You might see stories in the media about fnd that a specifc type of food upsets diets that claim to cure rheumatoid them, but this is quite unusual. If you do have a food The diets most likely to help are low in intolerance you’ll notice a fare-up in your saturated fats and high in unsaturated arthritis within a few days. We Complementary medicine recommend taking pure fsh body oil Many people with rheumatoid arthritis rather than fsh liver oil. Increasing your try diferent types of complementary intake of vitamin C may also help.

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For example order glucotrol xl 10mg with amex injectable diabetes medications weight loss, zones • Provide an additional form of evaluation that may “3B” and “4B” may be needed for vaccines if the vaccines have a black-market value—for instance glucotrol xl 10mg for sale blood glucose number chart, hepatitis B—or there is a particular problem with security for reveal defects in the warehousing system refrigeration equipment generic glucotrol xl 10 mg with amex blood sugar vs glucose. In cold because it greatly reduces the risk of a fre’s spreading to the climates, temperatures will drop below freezing in unheated main store. It must be ftted with an “explosion hatch,” Chapter 19 discusses items known to be sensitive to extreme which may be part of the roof or part of a wall. Fuel tanks should be placed inside a locked compound to prevent Storage at controlled temperature and humidity thef. The area enclosed should be sufcient to In hot climates, it is necessary to store many items in air- hold the total potential volume of fuel stored to ensure that conditioned rooms. In cold climates, tions, if a fre occurs, the risk of its spreading will be reduced. Vaccines, in particular, are to manage, because each stock item is always stored in the temperature-sensitive and must be kept at precisely con- same place, but they waste space. Fluid location systems trolled temperatures from the point of manufacture to the make better use of available space, but require sophisticated point of administration. This In a fxed location system, each stock item is allocated to material should be referred to for detailed technical advice. A fxed Table 44-3 summarizes the requirements for an efective location system is like a house in which each family member cold chain. A room is lef empty if a person is National and regional vaccine stores should be equipped not at home. Having backups ensures that large enough to accommodate the maximum possible level vaccines and other products are protected in the event of a of stock for every item, including safety stock. Secure storage With a fxed location system, stock administration is rela- tively easy. Narcotics and other controlled substances should be kept in However, this system has certain disadvantages— a secure room or in a safe. Ideally, a red warning light or warning bell that will activate when the door is unlocked • Fixed location systems are infexible. The keys to the secure store change in the quantity ordered or a change in packag- should be kept in a safe. Typically, one should be • If a new item is ordered, there may be no place to the director of the store, the most senior pharmacist, or the store it. Such precau- • Thef may increase because all store staf are familiar tions may also be needed for non-narcotic medicines that with the locations of valuable items. For example, many stores keep expen- • Storage space may be wasted, because at times it is sive products, such as antiretrovirals, in a secured space. However, picking stock is stored at In a fuid location system, the store is divided into many a convenient height, eliminating the need for mechanical designated locations. Another feature is that picking stock is always kept in the Rooms are assigned only when guests arrive. Unlike in a fxed location system, however, less A fuid location system uses available space efciently, but risk exists that changing requirements will disrupt the sys- it requires sophisticated stock administration. If demand increases for a particular item, the picking suggests that a store using a fuid location system can be 20 stock can be replenished more frequently. These data are recorded in the stock control sonnel to control stock, take periodic stock inventory, and system. Also, the stock record for each batch of each • Random bin item must always indicate the physical location of the item • Commodity code in the store. In a fuid location system, diferent batches of a particular item may be stored in several diferent places. In a fuid location system, clear organization and unique For example, if item number 150-050-48 is 500 mg amoxi- product identifcation are absolutely essential to the suc- cilline, 150-050-48: B1-B could be a batch of this product cess of the system. Coding by any stored in aisle B, bay 1, cell B, and 150-050-48: C2-B could one of the frst four methods is inappropriate for a fuid be another batch of the same product stored in aisle C, location system, because the position of a particular stock bay 2, cell B. For example, if antipyretics are Fluid location systems beneft immensely from the use randomly distributed about the store in a fuid location sys- of a computerized bin location and storage system, which tem, organizing the store on the basis of therapeutic class improves productivity and optimizes storage capacity. One of the advantages of a computerized Semifluid location stock control system is that records can be sorted in a variety of ways for diferent management purposes; for A semifuid location system is a combination of the fxed instance, according to therapeutic classes or in alphabeti- and fuid systems. Therapeutic or pharmacological category In a semifuid location system, each item is assigned a fxed space for picking stock. When an order is prepared, the Therapeutic or pharmacological classifcation may be an order-picking staf members know where to fnd each item. It is not an advantage in larger are restocked using items from the fuid locations. This method increases security but still allows the goods Alphabetical order (by generic name) is also attractive to be identifed by those staf members who have access to in peripheral stores that keep a small number of items. However, each change in the national (essential) medicines The location code is totally independent of the article list or in the level-of-use list requires reorganization of the code and is similar to the random bin principle. Tablets and capsules are stored together, with • The building where the product is located separate areas for oral liquids, injections, creams and oint- • Pack size ments, and topical liquids. Within each dosage-form area, • Pharmaceutical form products may be stored in a fxed, fuid, or semifuid manner and further organized by any of the other systems described in this section. Within each temperature and security zone, products must be stored so that they are easily accessible and protected Random bin against damage. There are four basic systems of storage: shelves, foor pallets, block-stacked pallets, and pallet racks. The random bin is a unique storage space identifed by a direct storage of cartons on the warehouse foor should be code. For example, a shelving unit can be divided vertically avoided because their contents may be damaged by moisture. The choice of system depends on the following factors— A unit of shelving might be labeled “B,” its bays “B1” and “B2,” and its shelves “A,” “B,” and “C. For example, items are placed and the skills to use and maintain it alphabetically within therapeutic classifcations. If there is more than one brand Pallets are generally used at the national and regional lev- of the same generic drug preparation, all are stored in the els, where products are stored in bulk. The funda- mental rule for pallet storage is that each pallet should be Commodity code used for only one product line. Pallets have the following advantages— Commodity coding is an abstract organizational system. It ofers maximum fexibility and can be used equally well in • They keep goods together and impose a disciplined small and large stores. This system is based on a unique article code combined • Large loads can be moved easily using mechanical with a unique location code. Article codes can be designed to specify therapeutic require any unpacking and repacking.

Abedon Phage-therapy Best Practices I: Basic Culture Collection buy cheap glucotrol xl 10mg diabetes mellitus nursing interventions, unless the goal is to Considerations characterize specific phage isolates purchase glucotrol xl 10mg managing diabetes. Phage-therapy publications should It is my premise that phage-therapy experi- provide sufficient detail on approaches mentation could benefit from a more rigorous employed for phage isolation including pharmacological approach purchase 10 mg glucotrol xl with mastercard diabetes test diagnosis. Although in part strengths, shortcomings and rationales increases in pharmacological rigour may be justifying their use; enriching for phages at addressed in terms of beter modelling of 37°C for use at 15°C, for example, should phage impact or greater consideration of represent an obvious error in experimental phage pharmacokinetics, in fact I am referring design. Alternatively, it is important for to much simpler as well as more achievable researchers to keep in mind that in situ phage practices, such as improved consideration of growth characteristics are relevant to phage basic microbiology, controls and experimental choice only if phage-therapy protocols are to design. In this section, I consider phage- be reliant on active rather than passive therapy best practice numbers 1–4, which treatment. This is because passive treatment address the issues of phage isolation, phage is dependent solely on phage bactericidal choice, phage characterization and disease effects rather than also depending on phage models. Of course, to a large this section before presenting, in subsequent degree, a demonstration of efficacy (positive sections, phage-therapy best practice num- results) in conjunction with phage-therapy bers 5–8 (controls) and then 9–12 (dosing and protocols will negate phage isolation enumeration). As will be discussed subsequently, however, not all phage therapy positive results are equivalently efficacious. Has a good strategy been used to isolation is that of host range, which I address isolate highly efficacious phages? As with chemical antibiotics, the first step in phage therapy development is the isolation of 2. Appropriate phages are those that are capable of killing bacteria From a pharmacodynamic perspective, under the expected in situ conditions. This phages should be chosen for phage therapy criterion should be viewed as basic to phage based not only on their ability to kill bacteria choice for phage-therapy use, with phage- but also in terms of their relative safety isolation protocols designed with this goal in (Abedon and Thomas-Abedon, 2010; Abedon, mind. With both of these use bacterial hosts and conditions that are criteria in mind, there are generally three well matched to the expected hosts and characteristics that should be avoided in environments during treatment, perhaps phage therapeutics, the first two perhaps especially the former (Abedon, in press). Isolation without enrichment, such as via These include an inability to display lysogenic direct plating of environmental or tissue cycles (i. A phage’s potential to display It is my view that this more stringent lysogenic cycles, however, may not always be characterization should not be an absolute obvious or necessarily easy to establish. For later-stage develop- that no bacteria will become phage immune ment of phage-therapy protocols, especially in the course of successful phage infection ones using human subjects, phage encoding (Fogg et al. By contrast, phages or their immediate descendants study of the phage potential to inadvertently (Hyman and Abedon, 2008); and (iii) non- transduce bacterial virulence factor genes via temperate phages ofen disrupt bacterial generalized or specialized transduction has chromosomes in a manner that makes not been a priority among phage-therapy generalized transduction less likely (Wilson researchers. In addition, where possible, been shown, as explicitly indicated in the propagation of phages in vitro for publications, to form clear plaques when subsequent use in vivo should be conducted plated on potential target bacteria (and, for a using bacterial hosts that lack virulence factor higher level of stringency, demonstration that genes. Has reasonable ex situ phage anti- centres, which serves as a marker for phage bacterial virulence been observed? Furthermore, not In vivo or in situ experimentation can be all temperate phages form lysogens on all expensive. In addition, in vivo studies can be bacteria they are capable of infecting subject to ethical considerations, and this is so productively. None the less, at a minimum, a even if such experiments have a reasonable failure to produce clear plaques should be likelihood of successful outcome. For human taken as a red flag with regard to the use of a testing, of course, these later considerations given phage isolate for phage-therapy are explicit, but issues of expense and purposes. The choice of using Although various authors have pre- temperate phages, however, must be justified sented in silico approaches to understanding in publications, and even defended. Given phage therapy processes, these methods are the association of bacterial toxin genes in neither well developed nor well tested for particular with temperate phages, it is also predictive accuracy (Gill, 2008). Less reasonable to expect greater levels of phage complicated approaches exist that can allow characterization by investigators who are researchers to calculate the minimum number using either temperate phages or phages that of supplied phages necessary to achieve are derived from temperate phages, that is, phage-therapy success (Abedon and Thomas- when employing phages that are not Abedon, 2010; Abedon, 2011a,b). These too, professionally lytic (Curtright and Abedon, however, are not always adequately robust 2011). This is additional characterization, means of phage characterization with regard particularly in terms of virulence factor to bacterial killing ability, as they may be encoding. Similarly, if biofilms are explicitly produced complete clearing of the bacterial serving as antibacterial targets, then a phage’s cultures was then recorded. In part, Alternative approaches to measuring a this is because the later readily determines phage’s bacterial killing ability have been only a few log reduction in bacterial density. Further- should be able to atain at least 4 log more, unless actively designed to do so, in reductions, in vitro, over reasonable spans of vitro assays are not necessarily a measure of a time (Kasman et al. Clearly, it is hard to defend moving up or otherwise more costly in situ experi- to in vivo testing using phages for which this mentation, phages should at least display in substantial amount of bacterial killing has not vitro therapeutic abilities, such as 4 log been or cannot first be demonstrated in vitro reductions in bacterial viable counts at phage using presumed in situ phage densities. In Thirdly, during in vitro testing, phage– any case, it is not so much that robust and bacterial community interactions should be effective in vitro phage characterization is followed over relatively short time intervals crucial to successful phage therapy develop- so that bacterial growth, giving rise to ment but instead that such efforts are cheaper, substantial increases in bacterial densities, less time-consuming and frankly more does not occur over the course of experi- humane than relying entirely on animal mentation. This means, in particular, that testing to characterize phage isolates for overnight incubations of phages with bacteria bacterial killing ability. Has bacterial colonization been typically preferable to end point determin- established prior to phage application? In particular, animal or other models that reasonably unless protocols have been designed represent the actual circumstances under specifically to test for the prevention of which phage therapy is envisaged. What initiation of bacterial infections (prophylaxis), constitutes a good model for in vivo or in situ then at a minimum multiple hours should phage therapy efficacy? At a minimum, effort separate bacterial challenge and subsequent should be made to make sure that bacterial phage addition (and if testing of prophylaxis colonization along with tissue invasiveness is envisioned, then phage addition should and other infection details occur to an extent precede bacterial challenge by a substantial that is similar to that seen with typical length of time rather than being simultaneous infection presentation (see, for example, Loc- or near simultaneous to bacterial application). For An alternative approach involves applying instance, if biofilms are normally present, and phages and bacteria to different body com- have developed for days, weeks or months partments, although determining whether prior to the onset of antibacterial treatment, such approaches are truly good models for then such biofilms should also be present in determining phage-therapy efficacy should the disease model employed to explore the be the subject of rigorous pharmacokinetic potential for phage-therapy efficacy (Ramage testing rather than simply assumed. The ultimate indication of poor technique in terms of failing to allow establishment of Discussion bacterial colonization prior to phage application is the mixing of phages with Given the above considerations, I envisage a bacteria prior to bacterial challenge, although logical four-step process of initial phage- simultaneous or even just short delays therapy development: (i) rational phage between bacteria and phage addition should isolation including in terms of avoidance of also be viewed as suspect. Indeed, ofen the temperate phages as well as the carriage of result of such practices is what appear to be virulence-factor genes; (ii) in vitro phage bacterial reductions only to below minimal characterization for anti-bacterial virulence; lethal densities rather than a ‘curing’ of (iii) in vivo or in situ proof-of-principle efforts existing disease. At a minimum, therefore, using models in which efficacy is highly effort should be made during phage-therapy expected while at the same time limitations experimentation to avoid mixing bacterial of technique may be identified (particularly challenges with phages in a manner that in terms of delays between bacterial challenge mimics phage–bacterial interactions as they and phage application); and then (iv) use of can occur in broth cultures. Usually such more realistic disease models to develop avoidance will be the case given substantial clinically useful therapeutic techniques, that delays between bacterial challenge and phage is, that improve on efficacy at or beyond the addition. In short, the field of further development of phage-therapy phage therapy, even in Western literature, protocols and/or a need for identification of has moved beyond the point of proof of more effective phages. Thus, would contrast with observation of reductions if animal experimentation is indicated, then in efficacy – given substantial delays between that experimentation really ought to be bacterial challenge and phage application – properly done. This means, perhaps more serving instead as study end points, as too than anything else, that effort should be ofen is the case in the phage-therapy made to improve the accuracy of disease literature. Abedon Ultimately phage-therapy protocols practice numbers 5–8, all of which involve need to be tested against naturally occurring questions of how to properly control as well infections, although in my opinion this as reduce biases during phage-therapy represents a later step in development. Step (vi) might then incorporate controls; that is, can a phage-therapy protocol, treatment of a small number of naturally under some approximation of the best of all occurring infections, representing essentially possible circumstances, achieve phage- a limited trial. Step (vii) would then entail a therapy efficacy even if it fails to do so under fairly substantial trial, perhaps under more other, perhaps more clinically realistic, real-world conditions. This Animal testing of the treatment of human would particularly be the use of an diseases, however, may not always be approximation of passive treatment, meaning extendable beyond step (v). A Pseudomonas ear infections (see Burrowes and good rule-of-thumb definition of ‘enough’, Harper, Chapter 14, this volume, for ref- whether provided by active or passive means, erences).