Oseltamivir an antiviral drug, slows the spread of influenza (flu) virus between cells in the body by stopping the

virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.51 day.[1] The drug is sold under the trade name Tamiflu, and is taken orally in capsules or as a suspension. It has been used to treat and prevent influenza A virus andinfluenza B virus infection in over 50 million people since 1999. Possible side effects Common adverse drug reactions (ADRs) associated with oseltamivir therapy (occurring in over 1% of clinical trial participants) include: nausea, vomiting, diarrhea, abdominal pain, and headache. Rare ADRs include: hepatitis and elevated liver enzymes, rash, allergic reactions including anaphylaxis, and StevensJohnson syndrome. Various other ADRs have been reported in postmarketing surveillance, including: toxic epidermal necrolysis, cardiac arrhythmia, seizure, confusion, aggravation of diabetes, and haemorrhagic colitis. There are concerns that oseltamivir may cause dangerous psychological, neuropsychiatric side effects including self harm in some users. These dangerous side effects occur more commonly in children than in adults. This stems from cases in Japan, where the drug is most heavily prescribed, consuming 60% of the world's production.[18] Concern has focused on teenagers, but problems have also been reported in children and adults. http://en.wikipedia.org/wiki/Oseltamivir#Possible_side_effects

Scientists are squabbling over the effect of virus inhibitor Tamiflu. While some say it is an important weapon in the battle against Mexican flu, others say this has never been proven. The effect of Tamiflu has not been researched enough, says epidemiologist Luc Bonneux of the Netherlands Interdisciplinary Demographic Institute. He says there is no proof that the virus inhibitor prevents serious complications from Mexican flu. But Jaap van Dissel from the Leiden University Medical Centre is convinced that it works. What bothers Mr Bonneux most of all is the so-called scientific research. In an article for the Dutch Journal of Medicine, he writes that one of the often-cited studies into Tamiflu's active substance, oseltamivir, was carried and paid for by the Swiss medicine manufacturer Roche. By coincidence, the same company which put Tamiflu on the market. Unreliable The Belgian epidemiologist thinks there is a lot wrong with the research. Mr Bonneux doubts whether the test groups in the Roche trial show enough similarities to be able to draw factual conclusions. He thinks Roche has presented the results in the most favourable light. He wants bigger and better studies to gain more certainty about the drugs effectiveness. In addition flu patients seldom develop complications, like pneumonia, not even high-risk patients. Therefore treatment is unnecessary.

Difficult research Jaap van Dissel, professor of infectious diseases at the Leiden University Medical Centre and a member of the Dutch Health Council, says Mr Bonneux is entitled to his own opinion. Research into the effectiveness of Tamiflu is just difficult, he says. Two groups of trial volunteers hopefully develop seasonal flu. One group is given medicine and the other is not, showing whether or not the medicine works. Ideally, because flu symptoms do not always mean someone has flu, says Professor Van Dissel. If the trial volunteer does not have flu, Tamiflu doesnt work either. The professor from Leiden believes Tamiflu is effective in the current pandemic. In a situation like this, you know it is flu. Then it appears that 80 percent of people in close contact with the patient are protected. Especially if it is taken straight away. The quicker the better. Commotion This is not the first time that Mr Bonneux has expressed his doubts about Tamiflu. In a commentary in the Belgian magazine De Tijd, he wrote earlier that it is only the pharmaceutical industry that profits from the medicine as remedy for mild flu, which H1N1 in fact is. The evidence that Tamiflu slows down the epidemic by a day, can, according to him, only be found in the virtual world of an obscure computer model. The telephone was red hot, says Mr Bonneux, surprised by the commotion his article caused. While I didnt actually say anything new. When the US Food and Drug Administration (FDA) approved Tamiflu in 1999, it doubted its effectiveness. The FDA considers the effectiveness of the medicine in people with a poor immune system or serious heart disease unproven. Clear considerations In addition Tamiflu is expensive, a relatively large number of people have to be treated to prevent infection and it only provides a limited amount of protection. A preventive dose of antibiotics works better, thinks Luc Bonneux. The complications of flu can cause more problems than the actual disease itself. Pneumonia can be treated with antibiotics. Then Tamiflu doesnt help at all. Although, he does not deny that the medicine is useful for people in high-risk groups, such as the elderly and the chronically ill. That is precisely Dutch policy, so I do not see the problem, says Professor Van Dissel. The Netherlands is much stricter than Great Britain for example, where Tamiflu can just be ordered over the Internet. Here it is only people in high-risk groups who are given a prescription, and they always have to consult a doctor. When the patients are children a doctor should take the decision whether or not to prescribe the drug. Professor Van Dissel sees few alternatives. We are not talking about a nasty bout of winter flu, this is a type of influenza which few people have developed immunity to. We know that a lot of people have to be treated to prevent the spread of the epidemic. Doing nothing is not an option. Mr Bonneux says the glass is half empty, we prefer to say the glass is half full. http://www.rnw.nl/english/article/commotion-over-tamiflu-does-it-work-or-not H1N1 viruses gain Tamiflu resistance without losing fitness Robert Roos News Editor

Mar 2, 2009 (CIDRAP News) Studies published today confirm that influenza A/H1N1 viruses have become widely resistant to oseltamivir (Tamiflu), the leading flu drug, without losing their ability to make people sickthereby underlining the need for new antiviral drugs. The findings also underscore the possibility that H5N1 avian influenza could gain resistance to oseltamivir, calling into question the value of stockpiling the drug in preparation for a potential flu pandemic, according to two experts who comment on the latest findings in an accompanying editorial. The research reports and editorial were released online today by the Journal of the American Medical Association. To the surprise of many, H1N1 resistance to oseltamivir rose sharply last year, reaching 12.3% in the United States and 16% worldwide. So far this season, it is far higher: more than 98% (321 of 325) of H1N1 isolates tested by the Centers for Disease Control and Prevention (CDC) were resistant to the drug. None of the H1N1 isolates have shown resistance to zanamivir (Relenza), the other flu drug in the neuraminidase inhibitor class. H1N1 is one of three flu subtypes that circulate each season, along with A/H3N2 and influenza B. Because of the spread of resistance, the CDC in December changed its recommendations on antiviral treatment for flu. For patients suspected of having influenza A, the CDC recommended using zanamivir or a combination of oseltamivir and rimantadine (an older flu drug in a different class) instead of oseltamivir alone. In one of the new studies, a team from the CDC and several state health departments compared people infected with oseltamivir-resistant and oseltamivir-susceptible strains of H1N1 last season and found no differences in patient characteristics, symptoms, or severity of illness. They report that four patients infected with resistant strains died. A second study describes an outbreak of resistant H1N1 infections in four patients in a Dutch hospital in February 2008. Three immunocompromised patients became ill after exposure to a patient who was sick with a resistant H1N1 strain, and genetic analysis showed that the viruses all matched, making it clear that the infection spread from person to person in the hospital. Taken together, the two studies "dispel the notion that oseltamivir resistance compromises virulence," states the accompanying editorial by David M. Weinstock, MD, and Gianna Zuccotti, MD, of Harvard Medical School in Boston. Resistance in 2007-08 US season The CDC-state study reports that oseltamivir resistance was found in 142 of 1,155 (12.3%) H1N1 viruses tested last season. Resistant viruses were reported in 24 states. Of the 142 patients who had resistant viruses, 99 supplied information. None of the 99 reported taking oseltamivir before being tested for flu, nor did they have close contact with others who had taken it. Four of the patients died, two of them in hospitals and the other two on the way to a hospital or in the emergency department.

After seven cases from one state were excluded, the authors compared 92 patients who had resistant H1N1 infections with 182 who had susceptible strains. They found no differences by age, sex, race, underlying medical conditions, or clinical symptoms. The analysis did indicate that patients with susceptible viruses were more likely to be hospitalized, but this difference disappeared when the two patients with resistant viruses who died before they could be admitted to hospitals were classified as hospital admissions. Before last season, oseltamivir resistance had been seen only in patients who were treated with the drug, the authors note, adding that it is unclear why oseltamivir-resistant H1N1 viruses emerged during the season and continue to circulate. "Additional options for the treatment and prophylaxis are critically needed," the report concludes. Hospital outbreak In the other report, the Dutch researchers write that three hospital patients apparently acquired oseltamivirresistant H1N1 infections from another patient who was found to have the virus while being treated for systemic lupus erythematosus. The three were in the same ward as the presumed index patient at the same time, though they never shared a room. Two patients, a hematopoietic stem-cell transplant recipient and an 89-year-old man, died of the illness. Genetic sequencing revealed that isolates from the four patients matched closely. All four had not only the H274Y mutation associated with resistance, but also a rare mutation known as T284A. Five healthcare workers got sick with flu-like symptoms while the index patient was hospitalized, but none of them were tested for flu, the report says. "This study confirmed that circulating H274Y-mutated A(H1N1) viruses can retain significant pathogenicity and lethality, as shown in these elderly or immunocompromised patients with lymphocytopenia, underlining the need for the introduction of new effective antiviral agents and therapeutic strategies," the authors conclude. Findings shouldn't be surprising "The widespread belief that oseltamivir would retain activity against epidemic influenza strains has crumbled, but this should come as no surprise," write Weinstock and Zuccotti, in the editorial accompanying the two reports. They say that surveillance over the past several years indicated that resistance was rising on a path that closely paralleled the rise of adamantane (amantadine and rimantadine) resistance 3 years earlier. Further, recent laboratory studies have shown that the H274Y mutation that confers resistance in H1N1 viruses does not necessarily interfere with the virus's ability to replicate in animal models, the editorial says. One corollary of the new studies, according Weinstock and Zuccotti, is that "oseltamivir resistance is likely to develop during the treatment of other N1-containing strains, including avian influenza A(H5N1). Thus, stockpiles to mitigate an influenza pandemic should not be limited oseltamivir."

Oseltamivir is the leading antiviral drug in national stockpiles for pandemic preparedness. The US stockpile is about 80% oseltamivir and 20% zanamivir, federal officials have said. Vaccination remains key tool Other experts said the findings show that vaccination remains the key tool for battling influenza. They share the concern about the risk of resistance in H5N1 viruses. "These developments further support the use of influenza vaccine as the cornerstone for influenza prevention and control," said Kathleen M. Neuzil, MD, MPH, a member of the Pandemic Influenza Task Force of the Infectious Diseases Society of America and director of the Influenza Vaccine Project at PATH in Seattle. Concerning the risk of resistance in H5N1, she said, "These recent findings represent a paradigm shift. We need to be prepared for the possibility that H5N1, or other influenza strains, could become resistant to oseltamivir and still be pathogenic and transmissible. This advocates for research and development into new antiviral and effective pandemic vaccines." Dr. Keiji Fukuda, director of the World Health Organization's Global Influenza Programme, called H5N1 resistance "a theoretical possibility." "So far, oseltamivir resistance has been rarely reported in H5N1 human isolates (three in Vietnam with H275Y mutation, two in Egypt with N294S mutation which confers mild reduction of oseltamivir susceptibility)," he commented by e-mail. "This is another situation where monitoring is essential." (The resistance mutation is sometimes called H275Y, depending on the naming system.) Fukuda observed that all the resistant H1N1 viruses tested so far have been sensitive to zanamivir and the adamantanes. "Of course, empiric therapy is difficult when you do not know the specific influenza virus type and subtypeas one typically does not in clinical practicebecause in some countries most of the circulating H3N2 viruses are resistant to adamantanes," he added. "But when national surveillance is good, empirically selected therapy is rational and possible." Both experts allowed for a possibility that H1N1 will eventually become susceptible to oseltamivir. "As these [resistant Brisbane-like] strains continue to evolve and be replaced by other strains, it's possible that the resistance will go down. This needs to be monitored," said Fukuda. Neuzil commented, "No one knows, but it [resistance] could certainly disappear as rapidly as it developed, as without widespread use of oseltamivir, it appears unlikely that antiviral pressure will favor resistant viruses." http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/mar0209osel.html Q. How does Tamiflu work? A. The influenza virus has a gene that is responsible for making a protein called neuraminidase which helps the virus to escape the cell it has just infected so it can attack another cell in the body. Tamiflu is a drug that blocks the action of neuraminidase and so inhibits the spread of flu virus from one cell to another. Tamiflu has to be taken early on in the course of an infection to stand a good chance of working well. It can also be taken prophylactically to limit the spread of virus in the body.

Q. How does a flu vaccine work? A. A vaccine works in quite a different way. A vaccine induces an immunity to whatever strain of flu is circulating. In the case of the H1N1 strain of swine flu, a vaccine would stimulate the production of virusfighting particles, or antibodies, directed against the haemagglutinin (H) proteins found on the surface of the virus. Once a person has been inoculated, the immune system will be primed to fight a real infection of the H1N1 strain when it comes along. Q. How easy is it to make a flu vaccine? A. The procedure is straightforward, but time consuming. The H1N1 strain of swine flu will be dismantled in a secure laboratory using reverse genetics its genes are cut up and separated. The genes responsible for the outer viral coat are then spliced with the genes of a harmless virus called PR8, and the recombined virus injected into fertilised hens' eggs. The eggs are incubated for days to let the virus multiply. Scientists then extract the fluid from the egg to isolate the virus. After splitting the virus with chemicals, the fragments are used to construct a vaccine. A laboratory vaccine can be made within four weeks, but industrial production can take up to six months. Q. How safe are influenza vaccines? A. Very safe. However, there was a bad experience in 1976 when a vaccine was developed against a swine flu outbreak. Some 40 million Americans were injected with the vaccine, which killed 25 and left 500 others with Guillain Barr syndrome, a serious neurological disorder. The vaccine turned out more dangerous than the original flu outbreak, which killed only one person. Q What defence do we have against swine flu? A Better than we did against the last pandemics in 1957 and 1968. We have a stockpile of anti-viral drugs Tamiflu and Relenza which we did not have then. We also have a pandemic plan, drawn up by the Government since avian flu became a threat in 2003, which sets out what is to be done from distributing the drugs and setting up helplines to closing schools and banning public events. Q Are there enough anti-viral drugs? A Not according to the Tories. The Government says it has over 30 million courses of the drugs, enough for half the population. The Tories say this is not enough if family members of an infected person are to be treated prophylactically. In that case, enough drugs to cover three-quarters of the population will be necessary, they say. Q How do anti-viral drugs work? A Two anti-viral drugs have been licensed in Britain in the last decade: Tamiflu and Relenza. The problem with the flu virus is that it is constantly mutating, so a new vaccine has to be produced each year. The antiviral drugs get round this by targeting not the virus itself but an enzyme that enables the virus to spread from cell to cell. Provided they are taken within 48 hours of the onset of symptoms they can shorten the illness and reduce its severity.

Q Why has the Government got drugs in its stockpile? A Because resistance has emerged in flu strains in some countries, rendering the drugs ineffective. Q What about a vaccine? A Pandemics tend to happen in waves separated by several months, so a vaccine could potentially be developed against the second or third wave, if they occur. A vaccine first has to be matched to the exact strain of the virus and then incubated in hen's eggs, which may take up to six months. Hundreds of millions of doses would be required which would put huge pressure on the world's laboratories. Q Shouldn't a vaccine be the first priority? A Previous vaccines against swine flu have turned out to be worse than the disease. An outbreak in the US in 1976 infected 200 people, of whom 12 were hospitalised and one died. But before it was over 40 million people had been vaccinated, 25 of whom died and 500 of whom developed Guillain-Barre syndrome, which can be fatal. --Q: What is swine flu? A: Much the same as human flu but in pigs. The worry is that pigs are excellent hosts for the virus. And because they are genetically close to humans, they can pass the virus to us more easily than birds can. The great fear over the past decade has been that the avian flu virus, H5N1, would infect pigs which would act as a reservoir for its transmission to humans. Luckily for the world, apart from a few isolated outbreaks, this did not happen. Q Has swine flu infected humans before? A: Yes. There have been rare cases since the 1950s, mostly in people such as farmers who work directly with pigs. In Europe, 17 cases have been reported since 1958. In the US, an outbreak at a military camp in New Jersey in 1976, infected over 200 soldiers, of which 12 were hospitalised and one died. Q What are the symptoms of swine flu? A: Similar to ordinary human flu cough, sudden fever, headache, muscle pains. In severe cases, it may lead to pneumonia, multi-organ failure, and death. The incubation period for ordinary human flu is two to five days. Q: Can it be treated? A: Yes up to a point. Early indications are that patients in Mexico and the US have been successfully treated with the antiviral drugs Tamiflu and Relenza. These drugs cannot prevent flu but they can limit its severity, and thus save lives, if taken as soon as symptoms develop. However, the swine flu has proved resistant to older anti-virals such as amantadine. Q: How can I protect my family?

A: By acquiring a stock of anti-viral drugs such as Tamiflu or Relenza, available only on prescription at an NHS cost of around 20 for a course of 10 doses (enough for one person). Otherwise, the best defence is strict personal hygiene. It is hard to better the advice printed by the 'News Of the World' on 3 November 1918: "Wash inside nose with soap and water night and morning; force yourself to sneeze night and morning, then breathe deeply. Do not wear a muffler, take sharp walks regularly and walk home from work; eat plenty of porridge." Porridge is, of course, a known cure-all but the rest of the advice holds as true today as it did then. Q: Is there a vaccine against it? A: Not in humans (there is in pigs). Ordinary seasonal flu vaccine for humans might offer some protection because there are similarities between the H1N1 human flu viruses and the new H1N1 pig flu virus. Investigations are under way to see if the seasonal vaccine would have a protective effect but those will "take some time". http://www.independent.co.uk/life-style/health-and-families/health-news/swine-flu-q-amp-a-is-tamiflundash-or-a-vaccine-ndash-the-answer-1676395.html

What is swine flu (novel H1N1 influenza A swine flu)? Swine flu (swine influenza) is a respiratory disease caused by viruses (influenza viruses) that infect the respiratory tract of pigs and result in nasal secretions, a barking-like cough, decreased appetite, and listless behavior. Swine flu produces most of the same symptoms in pigs as human flu produces in people. Swine flu can last about one to two weeks in pigs that survive. Swine influenza virus was first isolated from pigs in 1930 in the U.S. and has been recognized by pork producers and veterinarians to cause infections in pigs worldwide. In a number of instances, people have developed the swine flu infection when they are closely associated with pigs (for example, farmers, pork processors), and likewise, pig populations have occasionally been infected with the human flu infection. In most instances, the cross-species infections (swine virus to man; human flu virus to pigs) have remained in local areas and have not caused national or worldwide infections in either pigs or humans. Unfortunately, this cross-species situation with influenza viruses has had the potential to change. Investigators think the 2009 swine flu strain, first seen in Mexico, should be termed novel H1N1 flu since it is mainly found infecting people and exhibits two main surface antigens, H1 (hemagglutinin type 1) and N1 (neuraminidase type1). Recent investigations show the eight RNA strands from novel H1N1 flu have one strand derived from human flu strains, two from avian (bird) strains, and five from swine strains. What treatment is available for swine flu (H1N1)? The best treatment for influenza infections in humans is prevention by vaccination. Work by several laboratories has recently produced vaccines. The first vaccine released in early October 2009 was a nasal spray vaccine. It is approved for use in healthy individuals ages 2 through 49. This vaccine consists of a live attenuated H1N1 virus and should not be used in anyone who is pregnant or immunocompromised. The injectable vaccine, made from killed H1N1, became available in the second week of October. This vaccine is approved for use in ages 6 months to the elderly, including pregnant females. Both of these vaccines have

been approved by the CDC only after they had conducted clinical trials to prove that the vaccines were safe and effective. However, caregivers should be aware of the vaccine guidelines that come with the vaccines, as occasionally, the guidelines change. Please see the sections below titled "Can novel H1N1 swine flu be prevented with a vaccine?" and the timeline update for the current information on the vaccines. Two antiviral agents have been reported to help prevent or reduce the effects of swine flu. They are zanamivir (Relenza) andoseltamivir (Tamiflu), both of which are also used to prevent or reduce influenza A and B symptoms. These drugs should not be used indiscriminately, because viral resistance to them can and has occurred. Also, they are not recommended if the flu symptoms already have been present for 48 hours or more, although hospitalized patients may still be treated past the 48-hour guideline. Severe infections in some patients may require additional supportive measures such as ventilation support and treatment of other infections like pneumonia that can occur in patients with a severe flu infection. The CDC has suggested in their interim guidelines that pregnant females can be treated with the two antiviral agents. Tamiflu targets a protein called neuraminidase that lives on the flu virus cells. This protein helps the flu virus break through the cell walls so it can move on to other cells and replicate itself. Tamiflu inhibits the neuraminidase protein, so that the virus can't leave the cell to infect other cells. Eventually, the virus dies. Tamiflu can't stop the flu entirely. However, studies have shown that if you take it within 48 hours of showing symptoms, it can shorten the duration of the flu (strains A and B). Patients with the flu who took it felt better 30 percent (or 1.3 days) faster than people who didn't take it [ref]. The drug also can help protect you from getting the flu if you're exposed to someone who has it. But Tamiflu can't prevent the spread of the disease, and it won't stop illnesses (like the common cold) that resemble the flu. Tamiflu isn't cheap, either. A 10-dose course can cost $60 to $80 in the United States. Currently there is no generic version of the drug available in the U.S. Between 2004 and 2005, 12 children in Japan reportedly died after taking Tamiflu. However, the children also had neurological problems that could have been associated with the flu itself. In November 2005, the Pediatric Advisory Committee of the FDA ruled that the drug was safe for children [ref]. http://health.howstuffworks.com/medicine/medication/tamiflu.htm Jenner was operating on the now widely accepted principle that once a person catches a certain disease, he or she is immune to it for the rest of their life. For example, once you've had the chickenpox, it's extremely unlikely that you'll ever catch it again. This is because your body, when exposed again, will recognize the disease and fight it off. The beauty of vaccines is that they help the body develop disease-fighting abilities without making you sick. Vaccines accomplish this amazing feat by tricking the body into believing it already has the full-blown disease. Here are the steps in this process, known as the "immune response": The vaccine is administered. It contains weakened or dead forms of the disease. The immune system identifies these foreign substances (viruses and bacteria), also known as antigens. Once antigens are identified, the immune system develops proteins that circulate in theblood. These proteins are called antibodies. They fight the infection by killing the antigens. Antibodies are made by white blood

cells called lymphocytes, also known as B cells. The main purpose of B cells is to create antibodies to fight infection. The body stockpiles these antibodies so they are available to fight off the disease if exposed later on. Unfortunately, antibodies are disease-specific, so previously acquired chickenpox antibodies will be useless if faced with other diseases. It's very important to note that when the actual disease infects a person, the antigens multiply thousands and thousands of times until a raging infection is under way. The vaccine provides just enough of these antigens for the body to recognize them and complete the immune response process, therefore protecting them from exposure to the disease in the future. Vaccine Types Vaccines are usually given via a hypodermic injection, but some are given through the mouth or nose. There are two main groups of vaccines: live-attenuated vaccines and inactivated vaccines. Live-attenuated vaccines: Live-attenuated basically means alive, but very weak. These vaccines are made when the virus is weakened to such a level that they reproduce only about 20 times in the body. By comparison, natural viruses reproduce thousands of times. When the vaccine is made, the virus or bacteria is weakened in a laboratory to the point where it's still alive and able to reproduce, but can't cause serious illness. Its presence is enough to cause the immune system to produce antibodies to fight off the particular disease in the future. "Live-attenuated vaccines can cause very mild illness in a small proportion of people," says John Bradley, M.D., member of the committee on infectious diseases of the American Academy of Pediatrics (AAP). "However, these side effects are usually very mild and limited to a low-grade fever or runny nose." Dr. Bradley also notes that about 5 to 10 percent of children who receive the varicella (chickenpox) vaccine develop a few pox spots, but it's nothing compared to the full-blown illness. To weaken the virus, scientists must isolate it through a specimen from an infected person. They then grow the virus in a test tube. They "pass" the virus into a second test tube, then a third, a fourth and so on. Scientists perform this "passage" many times -- the measles virus was passed 77 times! The virus is periodically taken out of the test tube to see if it has mutated. Eventually, the virus gets so used to living in the comfortable test-tube environment that it loses its capacity to produce illness in humans. These passages are performed in a very controlled environment in exactly the same way each time. This discovery was considered the "hallelujah" of vaccine development, according to William Schaffner, M.D., professor and chair of the Department of Preventive Medicine at Vanderbilt University School of Medicine. Examples of live-attenuated vaccines are MMR (measles, mumps and rubella combination vaccine), varicella and the intranasal form of influenza. Inactivated vaccines: When inactivated vaccines are made, the bacteria is completely killed using a chemical, usually formaldehyde. Dead pieces of disease-causing microorganisms (usually bacteria) are put into the vaccine. Because the antigens are dead, the strength of these vaccines tend to wear off over time, resulting in less long-lasting immunity. So, multiple doses of inactivated vaccines are usually necessary to provide the

best protection. The benefit of inactivated vaccines is that there is zero chance of developing any diseaserelated symptoms -- allergic reactions are possible but extremely rare. Examples of inactivated vaccines are hepatitis A,hepatitis B, poliovirus, haemophilus influenzae type b (Hib), meningococcal, pneumococcal and the injected form of influenza. Why are some vaccines live and some dead? "The bottom line is that the decision is entirely driven by the science," says Dr. Schaffner. "If scientists can make a killed vaccine that is effective, that is what they will do. It's all about trial and error." Most viral diseases, he says, require live-attenuated vaccines, but the vast majority of bacterial illnesses are prevented with inactivated vaccines. There are some exceptions to this rule, though. For example: Some travelers to less-developed countries get the vaccine to prevent typhoid fever. There are live and killed forms of this vaccine. Rabies is a viral infection that is 100 percent fatal once it has progressed. The disease is simply too dangerous to give, even in a weakened state. Fortunately, science allowed the development of an inactivated rabies vaccine. http://health.howstuffworks.com/wellness/preventive-care/vaccine2.htm