Rabies vaccine

Rabies Vaccine Fails in Rare Death

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The rabies vaccine unexpectedly failed to save the life of a 6-year-old boy in Tunisia who was infected with the deadly virus, even though doctors started treating him the same day a stray dog bit him on the face, according to a new report of his case.
“It’s very rare to have the rabies post-exposure regimen fail, but there are cases where it does fail,” said Dr. Amesh Adalja, a member of the Infectious Diseases Society of America and a doctor at the University of Pittsburgh Medical Center, who was not involved in the child’s care.
The vaccine almost always works when the injections are delivered soon after a person is exposed to the rabies virus. It’s possible that the doctors failed to completely clean the dog’s saliva from all of the boy’s wounds. But even without such an error, there are rare instances in which the vaccine does not work in people, according to the case report, published Jan. 14 in the journal BMJ Case Reports.

After the dog bite, doctors immediately cleaned and treated the child’s wounds, according to the case report. They administered rabies immunoglobulin, which are antibodies that can fight the rabies virus; these were delivered both directly to the bite wound on his forehead as well as intravenously, into his bloodstream. They also injected the post-exposure rabies vaccine into his arm on the day it happened and on days 3, 7 and 14 after the bite, following World Health Organization guidelines.
But 17 days after the dog bite, the child came to the hospital with fever, vomiting, pink eye and signs of neurological problems, including crossed eyes, agitation, uncoordinated muscle movements and brisk reflexes in his legs. He died that day after developing seizures and going into cardiac arrest. [7 Devastating Infectious Diseases]
A later examination of the boy’s brain found that he had rabies, the researchers wrote in the report. Other tests showed that the dog that bit him also had rabies.
The virus that causes rabies travels along nerve cells until it reaches the brain, where it causes fatal swelling. Bites from rabid dogs cause more than 98 percent of the 40,000 to 60,000 cases of rabies among people that occur every year worldwide, the researchers said. Tunisia, in northern Africa, has one to two human rabies deaths a year, typically from people who do not seek treatment after being bitten by dogs.
Failure of the rabies vaccine is rare. In 1997, researchers reported at a conference that out of 15 million cases in which the vaccine had been used to date, it had failed in just 47 people, said Dr. Natasha Crowcroft, the chief of infectious diseases at Public Health Ontario, who was not involved with the care of the child in the recent case.
When the vaccine does fail, it’s not unusual for people to have been bitten on the hand or face, parts of the body that have a high concentration of nerves that the rabies virus can potentially infect. Moreover, the virus doesn’t have to travel far to the brain if it enters through a wound on the face, Crowcroft said.
Usually, “the rabies virus travels quite slowly to the brain up through the nerves,” she said. “When we give the vaccine, it’s a race of [the body] making antibodies from the vaccine and the virus traveling up to brain. As soon as the virus gets to the brain, it’s too late.”
The boy did not have hydrophobia (fear of water) or excessive salivation, two common rabies symptoms, when he returned to the hospital on day 17. “These features made the diagnosis of rabies encephalitis [swelling of the brain from rabies] difficult, especially in this child, who had received four doses of rabies vaccine” and other treatments, the researchers wrote in the case report.
It’s possible that the doctors missed a wound that was infected when they examined the child, and therefore didn’t properly clean and treat it with immunoglobulin, according to the case report. The doctors sutured the bite wound after cleaning and treating it, but if they missed some of the saliva, the suturing may have even helped the virus enter the nerves in the face, the researchers said.
Vaccines can also fail if they’re expired or not stored at adequate temperatures, but that didn’t happen in this case, the researchers said.
There is a pre-exposure rabies vaccine, but its high price makes it difficult to provide to people in developing countries, where many cases of rabies occur. Instead, only people who are at high risk of rabies, such as veterinarians, are usually given the pre-exposure vaccine, the researchers said.

Rabies Vaccine and Immunization Information

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Rabies is an acute and deadly disease caused by a viral infection of the central nervous system. The rabies virus is most often spread by a bite and saliva from an infected (rabid) animal (e.g., bats, raccoons, skunks, foxes, ferrets, cats, or dogs). In the United States, rabies is most often associated with bat exposures. However, there have been rare cases in which laboratory workers and explorers in caves inhabited by millions of bats were infected by rabies virus in the air.

Virtually 100% of those infected with rabies who do not receive the vaccine will die. Rabies illness includes rapidly progressing central nervous system symptoms such as anxiety, difficulty swallowing, and seizures.

Although less than ten human rabies fatalities occur in the United States annually, as many as 40,000 Americans receive the vaccine each year after contact with animals suspected of being rabid. An additional 18,000 people get the vaccine before exposure as a preventative measure.

Worldwide, at least 4 million people are vaccinated each year for rabies. The number of deaths that rabies causes each year is estimated to be at least 40,000, and as high as 70,000 if higher case estimates are used for densely populated countries in Africa and Asia where rabies is epidemic. India, with a very large population of stray, ownerless dogs, has about half of all cases of rabies worldwide. Between 30-60% of human rabies cases occur in children under 15 years of age.

Prompt wound care and the administration of rabies immune globulin (RIG) plus vaccine are highly effective in preventing human rabies following exposure.

Available Vaccines

The rabies vaccine is available as:

  • Human diploid cell vaccine (HDCV)
  • Purified chick embryo cell vaccine (PCECV)

Product: Imovax Rabies (HDCV for pre or post-exposure)
Manufacturer: Sanofi Pasteur
Year Licensed: 1980

Product: RabAvert (PCECV for pre or post-exposure)
Manufacturer: Novartis
Year Licensed: 1997

History of the Vaccine

The first rabies vaccine was developed in the early 1960’s. All rabies vaccines currently available for humans are made from killed rabies virus.

Who Should and Should Not Receive the Vaccine

Who should receive the vaccine pre-exposure?

  • Vaccination before exposure (pre-exposure) should be offered to people in high risk groups such as veterinarians, animal handler/caretakers, or laboratory workers who may be exposed to the rabies virus.

Pre-exposure vaccination may be considered for:

  • People whose activities bring them into frequent contact with rabies virus or potentially rabid animals (e.g., bats, raccoons, skunks, ferrets, cats, dogs).
  • Travelers who will spend more than one month in countries with a high rate of rabies infection, if they are likely to come in contact with rabid animals and immediate access to appropriate medical care is limited.

Who should receive the vaccine post-exposure?

  • Vaccination after exposure (post-exposure) is recommended for all individuals who have had contact with an animal (e.g., bites or abrasions) that they believe may be, or which is proven to be, rabid. Vaccination should be initiated as soon after exposure as possible and should be accompanied by proper wound management and the administration of Rabies Immune Globulin, human (HRIG).

Pregnant women who are exposed to rabies may receive the vaccine.

 

Who should not receive the vaccine?

  • The rabies vaccines are not recommended for routine use.
  • People who are moderately or severely ill should consult with their physician before receiving any vaccine.

Dose Schedule

Pre-exposure rabies vaccines are administered by a series of three injections:

  • The first dose may be given at any time
  • The second dose should be given seven days later
  • The third dose should be given 21 or 28 days after the first dose
  • Booster doses of vaccine are recommended every two years for those individuals who continue to be at increased risk of contracting rabies to maintain protective antibody levels. People that work with live rabies virus in laboratory settings should be tested every six months to ensure that they have adequate antibody levels, and receive boosters as necessary.

When post-exposure rabies vaccines are administered:

  • The number of doses required is determined by the previous immunization status of the individual
  • Previously unvaccinated people should receive the vaccine intramuscularly at 0, 3, 7, and 14  days. For adults the vaccine is given in the deltoid area; for children, it may be given in the anterolateral aspect of the thigh. In addition to rabies vaccine, these people should also receive rabies immune globulin (HRIG) at the same time as the first dose of the vaccine to provide rapid protection that persists until the vaccine works.
  • Previously vaccinated people should receive two doses of the vaccine intramuscularly—the first immediately, the other three days later. RIG is unnecessary and should not be given. An immunized person is anyone who has received a complete series of vaccine, or a person who has received a pre-exposure or post-exposure series of any rabies vaccine who has an adequate rabies antibody level.

Effectiveness of the Vaccine

There are no controlled trials of rabies vaccine. Among persons who had been bitten by an animal that was proven to be rabid and who received both HRIG and a full course of one of these modern rabies vaccines there have been no cases of rabies. Previously immunized people still must receive two additional doses of the vaccine if exposed to the virus, and the vaccine is almost 100% effective in these cases as well.

Although all rabies vaccines licensed in the U.S. induce protective antibody levels after three doses in nearly 100% of recipients, it is important to complete the dose schedules recommended for individual circumstances (see Dose Schedule). Previously, a 5-dose vaccine schedule was recommended but the dose that was given at 28 days is no longer felt to be necessary.

Known Side Effects

Mild reactions such as pain, redness, swelling, or itching at injection site are reported among 30%-74% of those vaccinated. Headache, nausea, abdominal pain, muscle aches, and dizziness are reported in 5-40% of those vaccinated.

Serious events after vaccination are rare. However, allergic reactions including swelling and mild difficulty breathing developed in 6% of patients who received booster doses of Human Diploid Cell Rabies Vaccine. In addition, three cases of neurologic illness resembling Guillain-Barré Syndrome, a progressive disorder affecting the nervous system, have been reported in people who received the Human Diploid Cell Rabies Vaccine. In these cases, all patients recovered within three months.

This vaccine is recommended by:

  • Advisory Committee of Immunization Practices of the Centers for Disease Control and Prevention
  • American Academy of Pediatrics
  • American Thoracic Society

What should you do if bitten by a rabid or suspicious animal?

1) Wash all bites and scratches immediately and thoroughly with soap and water and a solution that kills viruses (such as a povidone-iodine solution). Wound cleansing alone will markedly reduce the chances of getting rabies.
2) Go to a health care provider for a medical assessment regarding the need for a tetanus shot (if it needs to be updated), rabies vaccination, and administration of RIG, human. Two rabies immune globulins are licensed for use in the U.S. Each year approximately 18,000 people in the U.S. receive vaccination and immune globulin, and none of them has developed rabies.
3) Notify the state or local health department.

Vaccination and appropriate immune globulin therapy can protect you after you have been bitten. Vaccination before exposure merely simplifies therapy by eliminating the need for RIG and decreasing the number of vaccine doses needed.

Effective rabies control measures include routine immunization of dogs, cats, and ferrets, and control of stray dogs and selected wildlife. A fully vaccinated dog or cat is unlikely to become infected or to transmit rabies.

Key References and Sources of Additional Information

  • Centers for Disease Control and Prevention (CDC). (2008). Human rabies prevention—United States,2008: Recommendations of the Advisory Commission on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 57(RR-3).
  • Centers for Disease Control and Prevention (CDC). (2010). Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: Recommendations of the Advisory Commission on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 59(RR-2) .

Rabies Vaccine Dropped from the Sky

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Story at-a-glance

  • There are only 2-4 human rabies cases in the US each year, but annual prevention costs are more than $300 million
  • The Texas Department of Health is using helicopters to spread 100,000 rabies vaccines for skunks in the wilderness; other states have also conducted similar vaccination efforts
  • No one knows if such programs are effective or if the indiscriminate spreading of a pharmaceutical product into the environment is going to have any unforeseen consequences to wildlife or the surrounding ecosystem.
  • rabies

In 2009, there were just four human cases of rabies in the US. In 2010, there were two1… yet each year, the US spends more than $300 million for rabies prevention,2 which includes the vaccination of companion animals, animal control programs, maintenance of rabies laboratories and medical costs.

Even at the turn of the century, rabies-related human deaths only numbered around 100 annually, and by the 1990s, this had dropped to one or two.  While rabies is a serious, potentially deadly, illness, it is most often transmitted through the bite of a rabid wild animal – a risk factor that is negligible for many in the US.

Texas Department of Health Is Dropping Experimental Rabies Vaccines from the Sky

About 92 percent of the reported rabies cases in 2010 were in wild animals, including raccoons, skunks, bats, foxes, rodents and others. This poses a theoretical risk not only to humans but also to family pets, which could then transmit rabies to their owners.

Nonetheless, human rabies cases remain extremely rare… but efforts are still underway to knock out the rabies virus in wild skunk populations in Texas.

The Texas Department of Health is actually using helicopters to spread 100,000 rabies vaccines in two counties. The vaccines, which are contained in plastic cases coated with fishmeal to entice wildlife to eat them, are part of a pilot program to help reduce the number of rabid skunks in the area.

No one knows yet if the program is going to work – skunks will need to be caught and tested for rabies 30-60 days after the vaccines are dropped – or if the indiscriminate spreading of a pharmaceutical product into the environment is going to have any unforeseen consequences to wildlife or the surrounding ecosystem.

Should Wildlife Be Vaccinated Against a Disease That Infects 2-4 People a Year?

It’s also unclear why Texas is taking such aggressive measures against rabies. There has so far been only one reported case of human rabies in Texas in 2013, and the man was exposed in Guatemala, Mexico — not in Texas. The last case of human rabies in Texas prior to that was in 2009 and prior to that in 2004 – for a total of just 6 human cases in the last decade.3

For comparison, there were 2,390 cases of campylobacteriosis in Texas in 2012 alone… an illness largely spread by contaminated poultry raised on concentrated animal feeding operations (CAFOs). This illness, too, can be deadly if it infects a person with a compromised immune system, yet we’re not hearing about widespread efforts to curb its transmission…

Even if you factor in data from the US Centers for Disease Control and Prevention (CDC), which states there were 6,153 reported cases of rabies in animals in 2010, that’s for animals in the entire US, and not only skunks but also raccoons, foxes, bats and others. Texas isn’t the only state to opt for preventative rabies vaccination of wildlife, either. According to the Human Society of the United States (HSUS):4

“Federal and state wildlife officials have been vaccinating wildlife in many regions over the past 15 years. They distribute vaccine-laden baits that the target animals eat and thereby vaccinate themselves. Right now, oral rabies vaccination of wildlife focuses on halting the spread of specific types of rabies in targeted carrier species. Next, it’s hoped that this tool can shrink the diseases’ range.”

The end question remains the same, not only for Texas but for the entire US: is it really necessary to spend $300 million a year on rabies prevention… and what are the potential consequences of vaccinating wildlife?

What Exactly Is Rabies?

Rabies is a viral disease that most often enters your body through a bite or wound contaminated by the saliva from an infected animal. If it manages to infect the central nervous system, it can lead to early symptoms that include fever, headache, weakness and discomfort. As the disease progresses, it can lead to insomnia, anxiety, confusion, paralysis, hallucinations, difficulty swallowing, fear of water and death.

If you have been bitten by a wild animal (or a dog with unknown rabies status), wash the wound thoroughly with soap and water, as this will help to decrease your risk of infection.

Next, talk to a doctor about your next steps. He or she will probably contact the local or state health department and, if it’s deemed that the animal was rabid or at high risk of being rabid, you may need to start postexposure prophylaxis (PEP), which consists of a series of vaccines that can protect you from developing rabies. But remember, though rabies is serious, and frightening, it’s extremely rare. HSUS puts it into perspective:

“Given all the media attention that rabies regularly receives, it may be somewhat surprising to learn that very few people die from rabies nationwide each year. Over the past 10 years, rabies has killed only a total of 28 people in the U.S. This amounts to fewer than 3 fatalities a year nationwide.

People who contracted rabies in the United States were mostly infected by a bat. Most didn’t even know they were bitten. Some may have been sleeping when bitten. Others handled a bat bare-handed without realizing they’d been potentially exposed to rabies. But don’t panic over every bat sighting. Less than one-half of one percent of all bats in North America carries rabies. Although raccoons suffer from rabies more than any other mammal in the United States (about 35 percent of all animal rabies cases), only one human death from the raccoon strain of rabies has been recorded in the United States.”