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CDC Advisory Committee on Immunization Practices Unanimously Recommends Addition of a Second Dose of Chickenpox-Containing Vaccine to Childhood Immunization Schedule

June 30, 2006

Merck & Co., Inc. today announced that the U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) unanimously voted to recommend that children 4 to 6 years of age receive a second dose of varicella vaccine for the prevention of chickenpox. The Committee also recommended that children, adolescents and adults who received only one dose of varicella vaccine receive a second, “catch-up” dose, which can be accomplished through routine health-care visits and school- and college-entry requirements.

Merck’s VARIVAX(R) (varicella vaccine live (Oka/Merck)) and PROQUAD(R) (measles, mumps, rubella, varicella (Oka/Merck) virus vaccine live) are the only vaccines to protect against chickenpox in the United States. VARIVAX is indicated for vaccination against varicella in individuals 12 months of age and older and PROQUAD is indicated for simultaneous vaccination against measles, mumps, rubella, and varicella in children 12 months to 12 years of age. Chickenpox is highly contagious, easily spread, and sometimes can have serious complications - such as severe skin infections, pneumonia and encephalitis (swelling of the brain) that may result in hospitalization, or in rare cases, death.

“While use of the one-dose regimen of the chickenpox vaccine has significantly reduced cases of chickenpox, we believe we can still do more,” said Keith Reisinger, M.D., medical director, Primary Physicians Research. “Because clinical data has shown that a two-dose regimen can potentially further lower the risk of infection, the ACIP’s recommendation that children receive a second dose of the varicella vaccine makes it more likely that most American children can have even greater protection against this potentially serious disease.”

Chickenpox Remains a Serious Health Concern

Prior to the introduction of VARIVAX in 1995, an estimated four million people(1) were infected with the chickenpox virus each year in the U.S., with 11,000 requiring hospitalization.(2) In 1996, the ACIP and the CDC added the varicella vaccine to the list of recommended childhood vaccinations. PROQUAD was licensed in 2005 and provides an opportunity to administer simultaneous vaccination against measles, mumps, rubella and varicella, thus reducing the number of injections children receive and increasing varicella vaccination coverage to the national levels of coverage against measles, mumps and rubella, which is currently estimated to be 93 percent for children 19 to 35 months of age. Vaccination coverage rates for varicella still vary widely across states, from 70 to 94 percent in children age 19 to 35 months; in 2004, an estimated 12.5 percent of children were not vaccinated. Vaccination with VARIVAX or PROQUAD may not result in protection of all healthy, susceptible children, adolescents, and adults.

“Merck is proud that the use of our vaccines has contributed to the reduction in the incidence of chickenpox over the past 11 years,” said Mark Feinberg, M.D., Ph.D., vice president of Policy, Public Health and Medical Affairs, Merck Vaccines. “With widespread use of two doses of varicella vaccine, we hope to see fewer chickenpox outbreaks, especially in schools, and to we hope to see additional decreases in the number of children susceptible to the disease.”

The ACIP also voted to recommend that a second dose of varicella vaccine be included in the CDC Vaccines for Children (VFC) program. Since 1994, the VFC program has provided vaccines to children who are Medicaid-eligible, uninsured, underinsured or Native American.

Eligible children may receive recommended vaccines through VFC once the CDC contracts for the purchase of the vaccine.

Two Doses of Varicella Vaccine Lowered Risk of Developing Chickenpox in Clinical Studies

In a randomized, controlled study in 2,216 children 12 months to 12 years of age that compared one dose of varicella vaccine (VARIVAX) to two doses over a 10-year observation period, the estimated vaccine efficacy was 94.4 percent for one dose and 98.3 percent for two doses. During the 10-year observation period, this translates into a 3.3-fold lower risk of developing chickenpox more than 42 days after vaccination in children receiving two doses than in those who received one dose (2.2 percent vs. 7.5 percent, respectively). In this trial, 99.6 percent of children 12 months to 12 years of age who received two doses of varicella vaccine (VARIVAX) three months apart achieved a protective level of antibodies six weeks after vaccination compared to 85.7 percent of those who received only one dose. The duration of protection of VARIVAX is unknown.

Among 981 children who received two doses of VARIVAX three months apart and who were followed for 42 days after each dose, the two-dose regimen was generally well tolerated, with a safety profile generally comparable to that of the one-dose regimen. The incidence of injection-site complaints (primarily redness and swelling) observed in the first four days following vaccination was slightly higher post second dose (overall incidence 25.4 percent) than post first dose (overall incidence 21.7 percent), whereas the incidence of systemic complaints in the 42-day follow up period was lower post second dose (66.3 percent) than post first dose (85.8 percent).

Since 1964, the ACIP, a panel of 15 immunization experts, has provided guidance and counsel to the U.S. Department of Health and Human Services and the CDC on the most effective means to prevent vaccine-preventable diseases. The Committee writes recommendations regarding vaccine use among the pediatric population along with schedules regarding the appropriate periodicity, dosage, and contraindications applicable to the vaccines. In addition to varicella and human papillomavirus as recommended by ACIP earlier today, the ACIP currently recommends vaccines for routine use in children to prevent diphtheria, Haemophilus influenza type b, hepatitis A, hepatitis B, influenza, measles, meningococcal disease, mumps, pertussis, pneumococcal disease, polio, rotavirus, rubella and tetanus. Merck makes vaccines to help protect against nine of these 16 diseases.

Select Important Information about VARIVAX

VARIVAX is indicated for vaccination against varicella in individuals 12 months of age and older. Children 12 months to 12 years of age should receive a 0.5-mL dose administered subcutaneously. If a second 0.5-mL dose is administered, it should be given a minimum of three months later. Adolescents and adults 13 years of age and older should receive a 0.5-mL dose administered subcutaneously at elected date and a second 0.5-mL dose 4 to 8 weeks later.

VARIVAX is contraindicated in certain individuals, including those with: a history of hypersensitivity to any component of the vaccine, including gelatin; a history of anaphylactoid reaction to neomycin; blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems; an immunodeficient condition or receiving immunosuppressive therapy; active, untreated tuberculosis; active febrile illness; or those who are pregnant.

In children, adolescents, and adults monitored for up to 42 days, the adverse effects most frequently reported were as follows: fever, injection-site complaints, varicella-like rash (injection site), and varicella-like rash (generalized).

There are insufficient data to assess the rate of protection of VARIVAX against the complications of chickenpox (e.g. encephalitis, hepatitis, pneumonia) in children.

In a study in which children received two doses of VARIVAX three months apart, the two-dose regimen of VARIVAX was generally well tolerated, with a safety profile generally comparable to that of the one-dose regimen. The duration of protection from varicella infection after vaccination with VARIVAX is unknown; however, long-term efficacy studies have demonstrated continued protection up to 10 years after vaccination. Vaccination with VARIVAX may not result in protection of all healthy, susceptible children, adolescents, and adults.

Select Important Information about PROQUAD

PROQUAD is a combined attenuated live virus vaccine indicated for simultaneous vaccination against measles, mumps, rubella and chickenpox in children 12 months to 12 years of age. No clinical data are available on the safety, immunogenicity and efficacy of PROQUAD in children less than 12 months of age. PROQUAD may be used in children 12 months to 12 years of age if a second dose of measles, mumps and rubella vaccine is to be administered.

At least one month should elapse between a dose of a measles-containing vaccine, such as M-M-R(R) II (Measles, Mumps, and Rubella Virus Vaccine Live), and a dose of PROQUAD. If for any reason a second dose of varicella-containing vaccine is required, at least three months should elapse between administration of the two doses.

PROQUAD should not be administered to certain individuals, including those with: a history of anaphylactic reactions to neomycin; a history of hypersensitivity to gelatin or any other component of the vaccine; blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; an immunodeficient condition or receiving immunosuppressive therapy; active untreated tuberculosis; an active febrile illness (greater than 101.3(degree)F); or those who are pregnant.

In clinical trials with PROQUAD involving children 12 to 23 months of age, the most frequently reported injection-site adverse experiences (greater than 1% of children) were pain/tenderness/soreness, erythema, swelling, ecchymosis, and rash. The most frequently reported systemic vaccine-related adverse experiences (greater than 1% of children) were fever (greater than 102(degree)F), irritability, measles-like rash, varicella-like rash, rash (not otherwise specified), upper respiratory infection, viral exanthema, and diarrhea.

In a clinical trial involving 799 healthy 4- to 6- year-old-children who had received M-M-R II and VARIVAX at least one month prior to entry, 399 received PROQUAD and placebo, while 205 received M-M-R II and placebo concomitantly at separate injection sites. Another 195 healthy children were administered M-M-R II and VARIVAX concomitantly at separate injection sites. In the clinical trial described above, the rates of adverse experiences of injection-site reactions, nasopharyngitis, and cough, were generally similar among the three treatment groups.

Vaccination with PROQUAD may not offer 100 percent protection from measles, mumps, rubella and chickenpox (varicella) infection.

The duration of protection from measles, mumps, rubella, and varicella infection after vaccination with PROQUAD is unknown.

Posted by toshko under Herpes News | Comments (0)

Major KHV outbreaks hit UK fisheries

June 28, 2006

Three stillwater fisheries in the south and south east of England have been hit by the UK’s most serious outbreak of KHV ever.

The Centre for Environment, Fisheries and Aquaculture Science (Cefas) and the Environment Agency are investigating three outbreaks of Koi Herpes Virus at the three fisheries and have placed fish movement restrictions on the waters.

Cefas reports that the outbreak represents the first KHV mortalities reported this year and that it has been the most serious in terms of losses since the disease was first recorded in the UK.

The Environment Agency and Cefas are trying to determine the source of the outbreaks and identify whether any other waters have been infected by the deadly virus.

KHV, now formally known as Cyprinid Herpes Virus 3 or CyHV-3, is a member of the Herpesviridae family and has been responsible for mass mortalities in carp around the world, with Israel, Japan and South Africa particularly hard hit.

The disease occurs at temperatures between 15 and 28°C and results in mortality rates between 50 and 95%. It was first officially reported in the UK in 2000.

The virus can remain latent in infected carriers for long periods and only becomes symptomatic when the temperature rises to 15-28°C. As a result, dealers are advised to isolate newly imported carp and heat-treat them for several weeks in order to trigger the symptoms.

KHV is not yet a notifiable disease in the UK and Cefas now charges a fee to determine whether fish are infected with the virus. This may have led to a drop in the number of cases that get officially reported.

Posted by toshko under Herpes News | Comments (0)

Contagious Diseases

June 26, 2006

“The mission of Yambuku, with its schools, farms, and hospital, was still an island of efficiency and commitment in the midst of a dense, rain-soaked forest. At the end of August 1976, a lethal hemorrhagic disease, later known as Ebola fever, exploded out of the Yambuku hospital, devastating the mission and surrounding villages. An oasis of peace and order became a focus of terror and death.”–William T. Close, MD

Anyone who has endured an epidemic of strangles in a group of young horses, experienced the devastation of a herpes virus-induced “abortion storm,” or suffered through an outbreak of Salmonella knows the importance of understanding some of the nuances of contagious disease. The three diseases that will be discussed here are salmonellosis, herpes virus infection (rhinopneumonitis and encephalomyelitis), and Streptococcus equi infection (strangles). There are other contagious diseases, but these probably represent the three that have the greatest impact in North America. Although these three will be discussed in detail, the principles of prevention and containment are essentially the same for reducing the spread of most diseases.

It is extremely important that before discussing disease, certain medical terminology is accurately understood. There are many terms regarding the spread of disease that are used incorrectly and therefore alter the meaning, thus preventing a “true” understanding of the disease process. Words that are frequently misused are: infection vs. infectious vs. infective vs. contagious vs. contagion; and endemic vs. epidemic vs. outbreak. The science of studying infectious disease is called epidemiology. This science investigates the circumstances by which disease is spread throughout a population. The information is often vital in identifying the original source of disease, be it a sick animal, a carrier animal, or a contaminated feed source. It maps a pattern of the disease process and can be pivotal in the containment or prevention of a contagious disease.

There are many factors that must be considered with respect to an organism’s ability to cause disease and its ability to be contagious. The ability for a microorganism to cause disease is called “virulence.” The greater the virulence, the greater the ability to cause disease. Different strains of the same bacteria or virus can have a different degree of virulence. Two main factors associated with highly virulent organisms are the ability to attach and invade the body and the ability to survive the host’s immune system.

How Are Diseases Spread?

The first and foremost factor in disease spread is that a potential pathogen must get inside the body. Respiratory viruses generally are spread when an infected animal breathes, coughs, or sneezes the virus into the environment, then the virus is inhaled by a healthy animal. Bacterial diseases such as Streptococcus equi and Salmonella generally are spread from an infected animal via direct contact with infective material–either pus containing bacteria from abscessed lymph nodes or respiratory secretions in the case of strangles, or fecal material in the case of Salmonella. These “contacts” also can be made from an infected horse to a healthy horse via grooming tools, bedding, water/feed buckets, people’s hands, and so on.

Once contact has been made, the pathogen must attach to the tissue and invade in order to gain access to the body. To do this, it must overpower substantial barriers. Both the respiratory system and gastrointestinal system have many protective measures, but these barriers can be weakened or altered during times of stress, as will be discussed later.

If the pathogen makes it through the superficial protective barriers, it must then survive an encounter with the immune system before being successful at causing disease. Therefore, adequate vaccination can play an important role in disease prevention. (See article on vaccinations in The Horse of September 1996, page 41, and on the immune system in the August 1996 issue, page 34.)

Another concept that plays a role in disease prevention is that of “infective dose.” Different organisms require a different “dose” or amount to cause disease. In principle, if a person ingested a drop of Salmonella, most of the time that person wouldn’t get sick. But, if that same person ingested a tablespoon full–look out! Other microorganisms might require only the amount that would fit on a pinhead to cause disease.

The infective dose of a microorganism (the amount it takes to cause disease) can be considerably less in animals suffering from another illness, general stress, and/or immune system compromise.

The bottom line is that the less there is of the organism, the less chance there is of disease. So, cleaning and disinfecting and using quarantine procedures can be of significant benefit in preventing disease. (These will be discussed later.)

Salmonellosis

One disease that has killed many horses or resulted in very expensive treatment is salmonellosis (see related article on page 41). Salmonella has shut down many a riding stable, breeding farm, or veterinary clinic as it can be extremely contagious and zoonotic. The scare of having Salmonella on a property can last for years after the incident.

Salmonella is a bacterial infection that in adult animals targets the gastrointestinal system. There are more than 2,200 different strains (serovars) of salmonellae. Less than a dozen species typically cause disease in the horse, but the majority of Salmonella serovars have shown to be potential pathogens. In young animals (and occasionally adults), it can spread throughout the bloodstream (septicemia) and infect multiple organ systems. Salmonella in humans is associated with severe food poisoning, often related to improperly cooked poultry or the ingestion of raw, non-processed eggs.

The Salmonella organism itself is called a Gram negative type of bacteria. The outer wall structure of most bacteria differs between two large classifications–either Gram negative or Gram positive. The Gram nature of a bacteria is determined by the color they become when specially stained; Gram negative bacteria are red and Gram positive bacteria are purple.

One characteristic of Gram negative bacteria such as Salmonella is the presence of “endotoxin.” The endotoxin is part of the bacterial cell wall and is technically called the lipopolysaccharide component or LPS. The significance of this is that the effects of endotoxin on the body are great. The main effects are to decrease blood pressure and to decrease blood flow throughout the body. When you hear from your veterinarians that your horse appears “toxic” or is suffering from “endotoxemia,” it means the horse is showing clinical signs that can be attributed to the negative effects of endotoxin. Endotoxic “shock” is a potential component of Salmonella infection that can greatly complicate treatment.

Known associated “risk factors” for the development of salmonellosis in horses are co-existing gastrointestinal disease, concurrent disease and/therapy with antibiotics, transportation, and dietary change. Most “outbreaks” of Salmonella occur in summer and autumn–this might be related to the seasonal increase in risk factors (competition, transportation, and irregular feeding).

A previous report in the Journal of the American Veterinary Medical Association noted that intravenous antibiotic therapy or a combination of oral and intravenous antibiotic therapies increased the chance of developing salmonellosis by 6.4 and 10 times, respectively.

The defense mechanisms of the gastrointestinal system are complex. There is “local” immune system function, but in addition the “normal gastrointestinal microbial flora” plays an important role in protecting against invading pathogens. The horse’s colon or hind gut is essentially a vat of bacteria. Much of the digestive process is based on the normal population of bacteria (flora) digesting the raw fiber (hay) that would otherwise be indigestible–without bacteria, forage-eating animals would not be able to digest plant material.

The protective nature of this normal population of digestive bacteria is called “competitive inhibition,” as the few would have to compete with the many in order to survive. So, if only a few pathogenic organisms are ingested, there is a good chance they will be “competed out of existence” before causing disease. But, as the amount of pathogen ingested increases, there is an increasing chance it will establish an infection and cause disease–the pathogen thus reaches an infective dose.

As can be imagined, the bacterial “microenvironment” is very complicated and reaches a working balance dependent on numerous microorganisms and other factors. This delicate balance can easily be disrupted by sudden feed changes. As with any finely tuned fermentation process (e.g., beer, wine, pickle, or sauerkraut making), very subtle changes can really mess up the process. Changes in the carbohydrate content (e.g., sudden excessive grain feeding) can rapidly alter the fermentation process in the gastrointestinal tract and therefore alter the competitive inhibition action. These changes decrease the defense mechanisms of the normal microbial flora and can actually “select” for an increasing number of disease-causing organisms in the gastrointestinal tract.

It is therefore extremely important to avoid sudden feed changes–especially with respect to concentrates (grain). A horse’s diet should be maintained as consistently as possible and include an adequate amount of fiber (hay or grass). Any changes in feeding habit should be made gradually and a great effort should be made to avoid playing “musical feeds,” especially during times of other concurrent stresses. Bringing your horse’s normal feed with him to shows and events might reduce one of the overall stress factors. Many horses which are ultimately confirmed to have Salmonella have a history that includes transportation in the week preceding the development of disease and/or a recent change in feeding habit.

In the majority of circumstances, Salmonella is spread via “fecal-oral” transmission, i.e., any fecal material from an infected horse is a potential source of infection for other horses–and people too. As was mentioned in the basic principles section of this article, there is a “required” amount of Salmonella organism that must be ingested in order to cause disease. In normal, healthy adult horses, the “infective dose” is relatively high. But, in high-risk patients such as foals, sick horses, horses receiving antibiotic therapy, or horses suffering from transportation stress where the immune and other defense mechanisms might be compromised, the amount of organism necessary to cause disease is reduced.

One factor to consider with Salmonella is its persistence in the host. It has been shown that after infection the bacteria can be carried in the gastrointestinal tract and associated lymph nodes for months, thus creating a potential “carrier” state. During times of stress, that animal might develop diarrhea related to Salmonella infection or asymptomatically shed the organism in its feces. Given this, the most cautious approach would be to maintain a horse which was confirmed as having had Salmonella in some degree of isolation for several months. Repeated culturing of the feces could be helpful in determining when that animal stops shedding Salmonella organisms.

Many veterinary schools and private referral practices routinely culture feces from all hospitalized horses as part of a routine Salmonella control program. The reported number of horses which were “shedding” Salmonella organisms range from 1.4% to greater than 20%, with survey culturing of farms and stables indicating that 1-3% of horses could be expected to shed Salmonella. (None of these horses had diarrhea.)

Noah Cohen, VMD, PhD, Diplomate ACVIM, reported at the 1996 ACVIM meeting in San Antonio, Texas, on the use of polymerase chain reaction (PCR) technology to identify the presence of salmonellae in the feces of horses observed as either outpatients or hospitalized animals at Texas A&M University. Of 110 hospitalized horses which had fecal samples submitted to the clinical laboratory because the clinician caring for the case considered salmonellosis as a possible problem, 71 (64.5%) were positive by PCR. Of these 110 horses, 102 (92.7%) were admitted for colic or diarrhea. Cohen demonstrated the “the PCR was more rapid and sensitive than microbiologic culture for detecting salmonellae in fecal and environmental samples.”

Routine microbiologic procedures generally require 48-96 hours to obtain a preliminary result and up to seven days for confirmation. In addition to the time factor, it is more difficult to culture Salmonella from diarrhea than from firm feces due to the dilutional effect of the large volume of water being secreted into the gastrointestinal tract. Given the increased sensitivity of PCR and the potential for less than a 24-hour turnaround time, Cohen’s work in this area could be a very important advance in the ability to detect and control Salmonella.

Another factor to be considered regarding Salmonella is the organism’s ability to persist in the environment. It is known that bacterial survival in manure for up to one year is possible, with cool, dark, and damp conditions being best. Complete removal and isolated disposal from an environment of a horse which has been confirmed to have Salmonella or has had Salmonella can be very important.

Any horse which develops diarrhea has the potential to have Salmonella and should be treated as such until confirmed otherwise. The animal should be isolated as much as possible from other stock–especially foals–and reduction in environmental contamination should be attempted. (See section on Prevention And Containment.)

Equine Herpesvirus

Equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are the most clinically significant of the eight different equine herpes viruses that have been identified. EHV-1 infections can result in respiratory disease, abortion (”abortion storms”), fatal neonatal illness, and neurologic syndromes. EHV-4 primarily causes respiratory disease and sporadic abortions. Commercially available vaccines can protect against EHV-1 and EHV-4.

The respiratory form of EHV-1 and EHV-4 is usually characterized by fever (generally 102-106° Fahrenheit), nasal discharge, and coughing. (Coughing is not a consistent sign and might be completely absent.) The neurologic form of EHV-1 can either be associated with the respiratory form or can occur in absence of other EHV-1 syndromes. Horses afflicted with the neurologic syndrome typically show weakness and incoordination that starts in the hind end. Other signs often include loss of tail tone and a paralyzed bladder.

Abortion caused by EHV-1 infection can be either a sporadic single abortion or an epidemic “abortion storm” affecting all unprotected (unvaccinated) pregnant mares on a farm. The abortions are usually in late gestation (seven to 11 months) and typically occur in the absence of any respiratory signs. The aborted fetus shows characteristic pathology associated with herpes abortion, and virus can be isolated from many of the fetal organs.

Nasal secretions and aerosolized respiratory secretions (a sneeze) and anything that comes into contact with them are a major source of virus. Horses suspected of having equine herpesvirus should be isolated as much as possible and handled after all other horses. (See section on Prevention And Containment.)

With respect to abortion, it is actually the aborted fetus and the placental membranes and fluids that are a major source of the virus–these should be bagged (along with all contaminated bedding) and appropriately disposed of along with adequate cleaning and disinfection of the environment.

Streptococcus equi

Streptococcus equi is a bacteria that causes pharyngitis and lymph node infection of the upper respiratory tract only in horses, donkeys, and mules. Also known as strangles, the disease is most common in young horses, but horses of all ages can be affected. The bacteria does not survive well in the environment for long periods of time. The disease is highly contagious and is transmitted directly by nose or mouth contact or aerosol. Direct transmission can occur via any contaminated surface (water/feed buckets, people’s hands, grooming tools, etc.).

Clinical signs generally consist of depression, fever, nasal discharge, cough, inappetence, difficulty in swallowing, and subsequent swelling and tenderness of lymph nodes about the head. Complications occasionally associated with strangles are: obstruction of airway from lymph node swelling necessitating an emergency tracheotomy; infection of the guttural pouch; and the spread of infection to other lymph nodes within the body (bastard strangles).

Horses suspected of having strangles should be isolated as quickly as possible. (See section on Prevention And Containment.)

Prevention and Containment

Obviously, adequate vaccination programs for diseases that have a highly contagious nature are a paramount first step in the prevention process. This becomes increasingly more important as your animals or farm have increasing contact with other animals. Horses on the road traveling through many new and foreign environments or resident animals being exposed to such horses are at greater risk.

Farms that have a high volume of horses passing through, for either sale, training, or breeding purposes, have a greater risk for the resident horses to be exposed to contagious disease. Many larger farms, especially farms housing pregnant mares and/or foals, set up fairly strict isolation procedures for newcomers on the farm. The ideal situation is to have a separate barn so that there is a significant amount of “physical” space separating new animals. The incoming horses then can be monitored in their “quarantine” area for any signs of disease.

For up to two weeks they should be monitored for any coughing, sneezing, nasal or ocular discharge, swelling of lymph nodes about the head, development of fever, and/or development of diarrhea. During this quarantine time, they can also be brought up to speed on your vaccination and deworming programs before entering the general population.

The above “ideal” quarantine set-up is great if you have the extra barn to devote specifically to that purpose. But even if space is limited, some type of basic quarantine should be performed. In a one-barn stable, a single stall can be devoted to incoming horses, if possible in a corner without direct nose-to-nose contact with resident horses. I have seen a single, temporary stall placed in the corner of an indoor riding arena for this purpose. This will be less effective for respiratory diseases, such as influenza or rhinopneumonitis, that can be spread over substantial distances via aerosolizing of virus particles in nasal secretions, but it can help prevent the spread of more direct-contact diseases.

For farms that only have pasture and run-in sheds, a quarantine paddock can be set up for incoming horses. If two paddocks are adjacent, a “buffer” fence should be placed so that nose-to-nose contact between new and resident horses is prevented.

In all of the aforementioned quarantine setups, the incoming horses should be monitored for any coughing, sneezing, nasal or ocular discharge, swelling of lymph nodes about the head, development of fever, and/or development of diarrhea for a period of up to three weeks. Daily temperature monitoring for the development of a subtle fever might be the most sensitive “early-warning” sign as mild fever often precedes other signs of illness. All new animals should be handled after all the chores have been performed to the resident horses to minimize the potential of carrying a problem to the resident horses.

It is also important to remind everyone working with incoming horses on a farm that all the quarantine effort performed–no matter how great–is a waste of time if people, other domestic pets, brushes, sweat-scrapers, etc. carry a disease into the resident population of horses. In larger stables, a separate person can be assigned to the quarantine horses.

One problem associated with showing or eventing is that when you put your horses in their new, temporary abodes, you don’t really know who was there before or how good the cleaning procedures were prior to your arrival.

When I worked with show horses, we always arrived at the grounds early enough before the horses to thoroughly wash the stalls with a detergent cleanser followed by a spray-down with a chlorine bleach solution that had been diluted 1:10 with water. This procedure is the most effective if you allow the area to dry between washings and before placing bedding. We would also do this to the trailers.

This procedure by no means “sterilizes” a stall or trailer, but can reduce any clandestine pathogens to a less significant level. As many a great veterinary professor has quoted to students: “The solution to pollution is dilution.” So, at the very least, a simple stall wash-down is probably in order.

This cleansing/disinfecting is also recommended for contaminated stalls, water/feed buckets, stall cleaning utensils–essentially anything that has come in direct contact with a horse suspected of having a contagious disease. It is extremely important to cleanse an environment prior to disinfection. “Organic” material (feces) quickly inactivates most disinfectants, so it is important to minimize organic debris. Extremely porous surfaces are more difficult to disinfect because of all the nooks and crannies. Placing a smooth plaster/concrete layer over cinder-block, or a wood sealer to wood surfaces, will improve the efficiency of cleaning and disinfection.

There are a multitude of disinfectant products available commercially. Many of them will indicate on the label what they are best used for. Great care must be taken when using these as several types of disinfectant chemicals inactivate each other or can potentially produce toxic gases if mixed with chlorine bleach. In addition, there are some chemical disinfectants that are inactivated when in contact with certain detergent cleaning solutions, so adequate rinsing with water is important prior to the application of a disinfectant. Label directions should be implicitly followed and any questions should be referred to a professional.

Any horse which is sick and suspected of having a contagious disease should be immediately isolated from the healthy stock. If possible, a single person should be assigned to the care of this animal, and that person should be educated to use proper quarantine procedures. If this is not possible, the horse should be worked with last–after all other animals have been cared for. That animal should have separate feed/water buckets, grooming tools, stall cleaning utensils, etc.

In the case of strangles, where a draining abscess is involved, disposable rubber gloves should be worn. Any potentially infectious material (pus from strangles abscess, fecal material from a horse with diarrhea, etc.) should be handled with great care and disposed of appropriately.

If you have a sick horse you are caring for, or even healthy ones–especially foals–the act of hand washing can greatly reduce the spread of disease. Hand washing has been shown to significantly reduce the spread of disease in human hospitals, and it is a simple, basic procedure that should be done between the handling of different animals. In addition, this can greatly reduce the chance of spreading a disease such as Salmonella to yourself–rigorous hand washing should always be performed after contact with a horse which has diarrhea as a precaution. It is also recommended that disposable plastic boots be worn around quarantined animals in order to reduce the risk of spreading infectious material around the farm.

All of the aforementioned prevention and control actions are labor intensive and time consuming. But, when weighed against the devastation of an EHV-1 abortion “storm” or the economic losses encountered with a strangles or Salmonella outbreak at a boarding facility, they really are a small effort to put forth.

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FermaVir Announces New Preclinical Oral Bioavailability Data for FV-100, its Clinical Candidate for Shingles; Data Confirms Excellent Oral Bioavailability of the ProDrug in Another Preclinical Model

June 20, 2006

FermaVir Pharmaceuticals, Inc., (OTCBB:FMVR), announced today that new preclinical studies show that when its prodrug FV-100 is dosed orally, exceptional concentrations of active compound can be measured in the blood. These experiments showed that at the highest level of dosing required by the Food and Drug Administration in preclinical studies, levels of the active compound exceeded 50,000 (fifty-five thousand) times the EC50 for antiviral activity against varicella zoster, the causative virus for Shingles. The EC50 is a measure of the amount of a compound which inhibits 50% of the virus in vitro. Significantly, concentrations of the active compound remained well over 100 times the EC50 for over seventy-two hours after dosing. FV-100 is a novel antiviral drug candidate to address the potentially serious and debilitating viral condition known as shingles.

“We are extremely pleased with the latest data for FV-100. Not only does this data confirm our previous oral bioavailability data in another model but it also shows that single doses at the highest levels required by the FDA guidelines show no overt toxicity.” said Dr. Geoffrey Henson, CEO of FermaVir. “The data also suggests that we might be able to achieve once a day dosing. This would be very helpful when compared to the currently approved drugs for shingles on the market today which require three to five doses per day.”

The Company has initiated preclinical studies with its proprietary antiviral compound, currently known by its laboratory designation, FV-100, to be followed by clinical studies, as part of a long-term strategic plan for ultimate drug approval and commercialization. Research data suggests that the compound is believed to be 10,000 times more potent than currently approved drug treatments for shingles.

FV-100 is among a portfolio of FermaVir’s proprietary medical technologies and clinical candidates planned for development to treat a family of viral diseases related to herpes. Among FermaVir’s other lead drug candidates are powerful antiviral compounds to treat Cytomegalovirus, another potentially debilitating condition.

About FermaVir Pharmaceuticals, Inc.

FermaVir Pharmaceuticals, Inc. is an emerging biotechnology company positioned for rapid growth by developing important antiviral drugs and other treatments in underserved segments of the pharmaceutical development marketplace. The Company’s Intellectual Property portfolio includes a number of patent applications and a worldwide exclusive license for potential new drug treatments of infectious diseases. Among FermaVir’s lead drug candidates is a breakthrough antiviral treatment that has demonstrated powerful inhibitory activity and may have potential therapeutic benefit for the treatment of shingles, also known as herpes zoster. FermaVir’s proprietary compound is believed to be 10,000 times more potent than currently approved shingles drug treatments. FermaVir is also developing a compound that could provide the first improved effective treatment in years for Cytomegalovirus (CMV) infection, a currently incurable viral disease from the herpes family that can threaten eyesight as well as cause severe morbidity and mortality.

Forward-Looking Statements

Certain statements made in this press release are forward looking. Such statements are indicated by words such as “expect,” “might,” “should,” “anticipate” and similar words indicating uncertainty in facts and figures. Although FermaVir believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations reflected in such forward-looking statements will prove to be correct. As discussed in the Form SB-2 of FermaVir dated March 8, 2006,, actual results could differ materially from those projected in the forward-looking statements as a result of the following factors, among others: uncertainties associated with product development, the risk that FermaVir will not obtain approval to market its products, the risk that FermaVir technology will not gain market acceptance, the risks associated with dependence upon key personnel, and the need for additional financing

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Health Minute

June 14, 2006

As health care costs continue to skyrocket, a new report shows consumers could be saving big money simply by buying generic versions of the drugs.

The pharmacy tracking company Express Scripts did a study and found the highest savings could come from switching anti-cholesterol drugs like Lipitor and Zocor to their generic versions.

If everyone in the U.S. taking statins used generic brands, that alone would lower medical costs more than $10 billion every year.

The Food & Drug Administration says generic drugs must have the same “quality, strength, and purity” to be approved by the government, and they’re cheaper, too. With some leading brands costing as much as five times more than their generic counterparts, switching could mean substantial savings for many Americans.

A new drug called Sutent has been found to significantly help fight off kidney disease.

Kidney cancer is one of the deadliest cancers, with only 10 percent of patients surviving five years. Almost 40,000 Americans are hit each year with it, and about 13,000 die.

Two new studies of the anti-cancer drug Sutent finds the drug overall can help more patients with the disease than the standard interferon treatment, and can keep their cancer at bay for up to a full year longer after surgery.

One oncologist says the new results are nothing short of remarkable.

More than one million American men and women are infected with genital herpes every year, and the majority of them do not show any symptoms.

A study in San Francisco right now is trying out a herpes vaccine. The vaccine only works in women.

About 20,000 women across the United States taking part in the vaccine study. The study is a joint effort between the National Institutes of Health and GlaxoSmithKline.

The vaccine could be ready in about a year.

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Starving cancer cells

June 11, 2006

THERE appears to be a ray of hope that can lift the gloom surrounding cancer. Researchers in Australia have developed a drug that inhibits the growth of cancer cells by starving them.

The drug, called PI-88, works by impeding the creation of new blood vessels to tumour cells, thereby curtailing its blood supply and preventing them from developing any further.

This is in contrast to current methods of cancer treatment that targets the tumours directly by radiotherapy or chemotherapy. Additionally, curtailing the growth of blood vessels effectively cuts off means for cancer cells to spread. Tests done on animal subjects so far have been successful and the drug is at an intermediate stage of clinical development.

The heparanase hurdle

The development of PI-88 has its roots way back in 1985 when Prof Chris Parish of the John Curtin School of Medical Research (JCSMR) at the Australian National University (ANU) in Canberra demonstrated that there were high levels of heparanase activity present in malignant cancer cells.

Heparanase is an enzyme that is normally present in the human body, and works during embryonic development, wound healing and inflammation. The enzyme works by facilitating white blood cell entry into damaged or developing tissue. The white blood cells degrade the walls of the blood vessels, which in turn invoke the body’s natural healing process (utilising growth factors) to stimulate cell growth and hence aid tissue regeneration.

The abovementioned discovery found that cancer cells were hijacking the normal function of heparanase, and using it to promote its own growth and spread. One essential factor for the growth of cancer is the development of new blood vessels (known as angiogenesis) to the cancerous tissue. These not only supply blood to the affected tissue but also provide an easy method of transportation for cancer cells to invade the entire body though the bloodstream.

In 1991, Dr Craig Freeman joined the JCSMR, and began to study the heparanase enzyme in detail. There were several conflicting studies on heparanase at that time, according to him. “We had to start from scratch and develop a new, quick and simple way to detect the presence of the enzyme, and this had been a major impediment to studying heparanase.�

Although heparanase was first described 30 years ago, it was thought that the enzymes found in cancer cells and normal tissue regeneration were different. “We were one of the first to show that the various heparanase activities in cancer cells, immune system cells and probably in all cell types, were in fact the same. Much of the existing literature characterising heparanase activity was wrong!� explained Dr Freeman.

Cooking up the PI-88

Heparanase is essentially a degradative (or destructive, in not-so-accurate terms) enzyme that cells use to pass through blood vessel walls. Cell walls are supported by a membrane of a complex protein structure, which is bound together by a sulphated carbohydrate called heparan sulphate – think of it as bricks in a wall held together by cement.

Heparanase works to digest or break down the heparan sulphate, and with the glue holding the cell walls removed, the structure is destroyed and cells can pass through. Surrounding the blood vessel walls is a similar protein/heparan sulphate complex (the extracellular matrix), which contains growth factors that is released.

Normally, the body’s healing process kicks in by stimulating cell growth and repair, but in instances of cancer, blood vessels that feed the tumour are formed.

The goal was therefore to come up with a compound that could mimic the structure of heparan sulfate and bind to the heparanase enzyme, thus stopping its adulterated function.

As Dr Freeman described, the breakthrough came in 1995, when they identified an oligosaccharide (essentially a carbohydrate), which could be easily obtained in large quantities from yeast cell walls, and chemically modified it, adding sulphate groups (a sulphuric chemical compound) to allow it to mimic the structure of heparan sulphate. “This compound became known as PI-88 and was found to be a potent inhibitor of tumour growth by inhibiting heparanase activity and the action of the growth factors “ said Dr Freeman.

But the key advantage of PI-88 is that it has shown negligible toxicity levels in early human trials except for some small anti-coagulant activity. This is in contrast to side effects observed with other forms of cancer treatment.

Beyond cancer

PI-88 too has more potential than just a cancer drug. Many viruses such as HIV, herpes and dengue bind to cell surface heparan sulphates prior before invading the cells, and PI-88 or similar compounds can prevent this.

Dr Freeman added, “We are also involved with collaborations on the role of heparanase and heparan sulphate in diabetes, kidney disease, Alzheimer’s Disease and blood triglyceride levels.â€?

PI-88 was also shown to be an inhibitor of restenosis, which is the recurrence of narrowing in a coronary artery following the removal or reduction of a previous narrowing by balloon angioplasty.

A cure for cancer?

To provide funding to develop their initial discovery, ANU Enterprise, the commercial arm of the ANU, negotiated a deal with Progen Industries Ltd, an Australian biotechnology company to fund research which led to the development of PI-88. The company has provided A$4.3mil (RM12.2mil) over five years to JCSMR to support their work, and has guided PI-88 through several Phase I and II clinical trials, and is gearing up for the next stage, which will cost a staggering A$50mil (RM137mil).

More recently on May 16, Progen announced that it had received notification from the US Food and Drug Administration (FDA) guiding the accelerated development of PI-88. This essentially reduces the development timeframe of PI-88 by up to three years, which means that it could be available to the public earlier if the drug proves to be viable. But there’s one thing for sure – a cure for cancer can never arrive too soon.

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MediGene wins dispute over cancer-killing viruses patent

June 8, 2006

MARTINSRIED, Germany (AFX) - MediGene AG said it has successfully won a dispute over its patent on herpex simplex viruses, or cancer-killing HSV, at the European Patent Office.

The patent protects a production method for herpes simplex virus-1 vaccines including specific oncolytic herpes simplex viruses (cancer-killing HSV) developed by MediGene.

University College London and the University Court of the University of Glasgow had opposed the patent.

The patent protection will expire in Sept 2011, but in case of marketing

authorization prior to that date, the protection may be extended by up to five years.

MediGene is developing two strains of oncolytic herpes simplex viruses, designed to selectively multiply in tumor cells, thus destroying the tumour.

The NV1020 strain is currently undergoing a clinical phase I/II trial for the treatment of liver metastases from colorectal carcinoma, and the G207 strain is being examined in a clinical phase I trial for the treatment of malignant brain tumour.

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Red, flaky spots, moles that bleed — most people ignore these symptoms to avoid surgery.

June 5, 2006

Efforts are under way to control a herpes-like virus which is killing abalone off the south-west Victorian coast.

The disease, ganglioneuritis, has been detected at four farms in south-west Victoria and at Flinders near Port Phillip Bay, with millions of dollars worth of stock having to be destroyed.

Fisheries Victoria says the disease has now escaped into the wild off Port Fairy.

Fisheries executive director Peter Appleford says although a similar disease devastated the abalone industry in Taiwan in 2003, he is hopeful control measures will stop a further spread here.

“What we’re looking at is to put some controls in place along the coastline to limit the activity there,” he said.

“We believe the main risk for the transmission of the disease over the large part of the state will be by human activity so it will be to try to limit human activity in that particular area, in particular abalone diving, whether commercial or recreational. We’re also looking at other access controls as well.”

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UMass Medical School Partners with Powdermed to Test Potential Avian Flu Vaccine

June 3, 2006

PowderMed also licenses fundamental UMMS technology for DNA vaccines to advance breakthrough treatment for annual flu virus.

WORCESTER, Mass., May 31, 2006 — The University of Massachusetts Medical School today announced a partnership with British immunotherapeutics company PowderMed to advance the development of a potential vaccine for avian flu. Under the agreement, PowderMed’s leading DNA vaccine candidate for avian flu (H5) will be tested and analyzed in the lab of Shan Lu, MD, PhD, professor of medicine and leader of the UMMS DNA vaccine efforts.

Dr. Lu was part of the UMMS team which pioneered fundamental elements of DNA-based flu vaccines in the 1990s. “We are very pleased to be working with PowderMed to help evaluate this vaccine candidate in hopes of speeding its entry into the clinic,� Dr. Lu said. “At UMass Medical School we have focused many years of effort on developing DNA-based vaccine technology, because the world desperately needs a better way to target not only flu, but many infectious diseases.�

PowderMed is recognized as the international leader in the development of a new class of vaccines for flu. Results to date suggest that PowderMed’s proprietary prophylactic DNA-based vaccine will provide defense against influenza. PowderMed will initiate phase II studies using both bird flu strains and annual flu strains in 2006. Dr. Lu’s lab will analyze the avian flu vaccine’s ability to generate a protective immune response in animals. There will be no live avian flu virus involved in the work—only the DNA-vaccine candidate.

“UMass Medical School has a rich history in DNA vaccine research, and PowderMed is pleased to help continue this tradition through this latest collaboration,� said PowderMed CEO Dr. Clive Dix. “Through ground-breaking research and technology, we are creating the potential for DNA vaccines to significantly limit the burden of disease. The advantage of a DNA-based approach is that the vaccines can be manufactured very rapidly and in large quantities, while producing an extremely good immune response at low doses.�

In addition to the collaboration with Dr. Lu for the avian flu program, PowderMed has licensed certain patent rights related to the DNA-vaccine technology platform developed at UMass in the 1990s. That work, led by former UMMS Professor Harriet Robinson, PhD, in collaboration with colleagues at St. Jude’s Children’s Research Hospital in Tennessee, is widely viewed as seminal work in the development of DNA-based vaccine technology. Dr. Lu, who was part of the team in Dr. Robinson’s lab at the time, has continued to advance the science of DNA-vaccine technology in his own lab at UMMS, developing other potential vaccine candidates for HIV, seasonal flu (H1 and H3) and potential new pandemic flu including avian flu H5 viruses.

“In addition to the quick manufacturing time and ease of storage and administration of DNA-based vaccines, there is growing data that gives us hope that the immunity they generate may be longer lasting,� said Dr. Lu. “So for many reason, we believe that DNA-based vaccines are an important next-generation step in combating infectious diseases.�

Traditional flu vaccines use weakened elements of the actual flu virus in their composition and take many months to produce in large scale. Scientists are forced to predict months in advance the likely strain of flu that will circulate each year, then take samples of those viruses and grow them in massive numbers of chicken eggs. The process can’t respond rapidly to a different emerging strain of annual flu, or a potential pandemic of a mutated avian strain.

DNA-based vaccines work in a completely different way. They employ snippets of DNA constructed in the lab that match genetic elements of the flu virus. When the DNA-vaccine is administered, it begins to express the protective proteins, which the host recognizes as part of flu, thereby initiating an immune response.
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About UMMS: The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $174 million in research funding annually, 80 percent of which comes from federal funding sources. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information visit www.umassmed.edu.

About PowderMed Ltd – http://www.powdermed.com/ PowderMed is a private immunotherapeutic company based in Oxford, UK. The Company is focused on the clinical development and manufacture of therapeutic and prophylactic DNA-based vaccines for viral diseases and cancer. The company has four clinical and three pre-clinical stage projects. The lead clinical program has shown positive Phase I results in the treatment and prevention of human influenza. This technology is uniquely and easily adaptable to treat avian flu and to address the pandemic threat. PowderMed also has a product for the treatment of genital herpes in Phase I trials, and two partnered Phase I
programs, one in Cancer (Ludwig Institute) and the other in HIV/AIDS (Glaxo SmithKline). PowderMed vaccines are delivered using PMEDTM (Particle mediated epidermal delivery), a needle-free, virtually painless delivery system that requires minimal medical training, allows self-administration and requires no refrigeration for stockpiling. Specifically, PowderMed’s technology delivers DNA to the epidermal layer of the skin where it is presented to the cells of the immune network, thereby creating immunity and thus facilitating both treatment and prevention of disease.

PowderMed has adopted a flexible and cost effective business strategy; company resources are used for discovery research and drug design with outsourced partners being used for its drug development and manufacturing requirements. The Company has a highly experienced management team that has a combined 160 years of experience, with Rolf Stahel as the chair of the board. The Company has raised £20 million in venture financing to date, from its existing investor syndicate that comprises Abingworth Management, Advent Venture Partners, Isis College Fund, Oxford Bioscience Partners and SV Life Sciences.

PowderMed’s Influenza Vaccines
PowderMed DNA vaccines are made up of two components – the vaccine-specific DNA and the delivery device. The DNA vaccine consists of the standard DNA backbone with an immunologically active gene specific to each viral strain – the gene cassette. The delivery device is a fully developed and patented system, called Particle Mediated Epidermal Delivery (PMED™), whereby gold particles coated in the vaccine DNA are propelled into the skin using high-pressure helium. In this way, vaccine DNA is delivered directly to cells of the immune network in the skin, thereby stimulating immunity. This approach provides a rapid route to vaccine development that can be applied to existing and emerging flu strains including, for example, the threat of the emergence of a pandemic flu strain.

Results of previous preclinical and clinical testing of PowderMed’s DNA-based influenza vaccines, including H3 and Avian H5 strains utilizing PMED, show consistent and robust immune responses in animals and humans at microgram doses.

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Knowledge Of Infection May Prevent Spread Of Herpes Virus

June 1, 2006

Main Category: Sexual Health / STDs News
Article Date: 31 May 2006 - 0:00am (PDT)

A new study suggests that the risk of transmitting the virus that causes most cases of genital herpes could be cut in half by more testing and informing sexual partners of infection. The study is published in the July 1 issue of The Journal of Infectious Diseases, now available online.

Until recently, there was little evidence to show that knowledge of infection would lead to decreased transmission of herpes simplex virus (HSV) to others. But Anna Wald, MD, MPH, and colleagues at the University of Washington and the Fred Hutchison Cancer Research Center in Seattle studied 199 patients with newly acquired genital HSV-2 infection and found that patients were about half as likely to transmit the virus when they knew they had genital herpes and informed their sexual partners.

According to Wald, “these findings suggest that testing persons with HSV type-specific serologic assays and encouraging disclosure may result in decreased risk of HSV-2 transmission to sexual partners.”

The importance of this finding is described by editorialists Edward Hook III, MD, of the University of Alabama at Birmingham and Peter Leone, MD, of the University of North Carolina at Chapel Hill as one of three effective tools to prevent the spread of this sexually transmitted disease (STD). “Genital herpes is one of the few common STDs for which, at present, there is little coordinated emphasis on control efforts,” say Hook and Leone. The two experts also support suppressive antiviral therapy and condom use as the other necessary elements to control the spread of genital herpes nationwide.

This most recent study also found that most people who transmitted HSV did not know that they had genital herpes. Wald, Hook, and Leone suggest that physicians should not only increase testing for HSV, but should also counsel their patients about transmitting the virus and disclosing their HSV status to sex partners.

Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Alexandria, Va., IDSA is a professional society representing about 8,000 physicians and scientists who specialize in infectious diseases.

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