September 15, 2008

 

 Reserves of human-use rabies vaccine could alleviate supply worries - September 15, 2008

 
posted September 1, 2008
 
Vaccine vials
Vaccine supply is low while one supplier reports that demand is unexpectedly high
 

The nation's two human-use rabies vaccine suppliers haven't kept pace with demand, and recent use could limit postexposure prophylaxis availability.

An uptick in rabies infections, a swing in the human plasma market, or failure of a human-use vaccine lot to pass regulations could further hurt the nation's vaccine supplies.

Public health officials have talked for years about creating a vaccine reserve.

"It's not a novel concept, and we should be past the talking stage," said Dr. Charles Rupprecht, chief of the Centers for Disease Control and Prevention's rabies program. "We should have a plan like this in place."

But starting such a reserve requires fighting fiscal restraints and public perception, he said. And he does not think the concept will become a reality without a large amount of support.

People generally don't think of rabies as a preventable disease for humans, considering it more of a problem among wildlife and dogs, Dr. Rupprecht said. And current economic conditions may outweigh the validity and utility of a reserve, he said.

"Who's going to pay for it and how?" Dr. Rupprecht said.

State and federal authorities, along with vaccine manufacturers, have been restricting vaccinations since May.

Dr. Richard Franka, a microbiologist for the CDC, said there has been enough vaccine for people exposed to the virus. But pre-exposure vaccinations have recently been limited to people at greatest risk, such as veterinarians, wildlife biologists, and laboratory workers.

Rabies vaccine for humans was not available from one of the nation's main suppliers, Sanofi Pasteur, at press time in mid-August. The other main supplier, Novartis, has been requiring risk assessments before releasing doses, according to an Aug. 22 CDC update sent to clinicians.

"To ensure that thorough risk assessments are conducted, Novartis is now requiring that health care providers confer with public health officials, and obtain a confirmation code from a state health department before ordering vaccine doses for post-exposure prophylaxis," the update says.

Novartis officials recently notified the CDC that its vaccine, RabAvert, was being used at a higher rate than expected, and the use could limit near-term availability of vaccine for postexposure prophylaxis, the CDC message says.

"The CDC strongly recommends that health care providers, state and local public health authorities, animal control officials, and the public take immediate steps to ensure appropriate use of human rabies biologics," the messages says, later adding, "Judicious and appropriate use of rabies vaccines is crucial to avert a situation in which persons exposed to rabies are put at increased risk due to depleted vaccine supplies."

Supplies of rabies vaccine fell after Sanofi Pasteur started renovations in June 2007 in its IMOVAX rabies vaccine production facility in France, according to information from the CDC. The renovations are intended to maintain compliance with FDA and French regulations, and the facility is expected to be operational by late 2009.

Sanofi Pasteur produced inventory of its vaccine on the basis of historical demand, according to the CDC. But Novartis fell short of projected production of RabAvert earlier this year, according to the CDC.

Officials with Novartis wrote a letter, which is posted on the CDC's site, which says in part they are working with the FDA, CDC, and National Vaccine Program Office to manage and increase the supply of RabAvert.

"We anticipate additional vaccine supply availability by the fall and will work with the CDC to ensure its availability for pre (sic) and post-exposure prophylaxis," the letter says.

World Rabies DayWorld Rabies Day
"The World Rabies Day initiative is really a mechanism for the development and support of the appropriate infrastructure both of veterinary and public health. And so, the campaign advocates for the health of the whole population—human and animal."

– PETER COSTA, GLOBAL COMMUNICATIONS COORDINATOR FOR THE ALLIANCE FOR RABIES CONTROL
 
Novartis Vaccines broke ground in May for a new rabies vaccine production facility in Germany, the letter says. The plant will produce supplies for the U.S. and it is expected to be operational in 2011.

An Aug. 11 announcement from the CDC indicated Sanofi Pasteur may have vaccine available by late September or early October. Novartis is expected to have more doses available in October.

"We think things are going to get better," Dr. Franka said. "But since there are only two manufacturers providing vaccine for the U.S. market and there is no storage or reserve, we cannot be sure."

The CDC is recommending veterinarians, public health authorities, and health care providers educate the public about how to avoid rabies exposure and what to do if exposed.

World Rabies Day Sept. 28

Rabies killed one person in the U.S. in 2007 and one in the first four months of this year, according to statistics in "Rabies Surveillance in the United States in 2007," a report starting on page 884 of this issue of JAVMA. There were three reported cases in 2006.

Confirmed cases of rabies in animals in the United States and Puerto Rico rose about 4.6 percent from 2006 to 2007, totaling 7,258 last year, the report says. The rise coincided with a 7 percent increase in the number of animals tested.

Though about 48,000 people in the U.S. are exposed to rabies annually, postexposure prophylaxis remains available and few die from infection, said Abbigail Tumpey, a spokeswoman for the CDC. Rabies kills about 55,000 people worldwide every year, she said.

Organizers of World Rabies Day, occurring Sept. 28, hope to lower the infection rate by raising worldwide awareness of the zoonotic disease, its prevention, and how to combat reserves of the virus in animal populations. The second annual event is expected to include meetings at schools in the Congo, mass vaccinations of cats and dogs in Tanzania, free vaccination and education in Syria, and educational and fundraising runs in the U.S., according to information from the Alliance for Rabies Control.

AVMA staff members will help the Alliance for Rabies Control develop and distribute educational materials for the event. The AVMA Executive Board approved the partnership in April.

Other U.S. events include educational programs in Wisconsin, an information giveaway and vaccination clinic in Virginia, and African lunch day at Schering-Plough cafeterias.

Peter Costa, global communications coordinator for the alliance, described the organization's events as "the essence of 'one health' in action."

"The World Rabies Day initiative is really a mechanism for the development and support of the appropriate infrastructure both of veterinary and public health," Costa said. "And so, the campaign advocates for the health of the whole population—human and animal."

Costa said there were events in 74 countries during the Sept. 8, 2007, event, and broadcast messages reached more than 54 million people. He said his organization has received inquiries about the day from 181 countries this year, and he expects more people will be reached with educational messages than in 2007.

"We have weeklong events that incorporate vaccination clinics, educational campaigns, parades, and school classroom lessons for children," Costa said. "And we also see media blitzes that go out through television authorities, where maybe we'll see a ministry of health or a government that will actually come on public broadcasting and provide a rabies education message."

Cases of rabies in humans are still most prevalent in locations including China, India, and the Philippines, Dr. Rupprecht said. In sub-Saharan Africa, rabies surveillance is "less than ideal," he said.

Children worldwide are at the highest risk because they are most likely to interact with infected dogs and become bitten in high-risk areas such as the face or neck, Tumpey said. Dogs remain the main global reservoir of rabies, despite elimination of the canine rabies virus variants in the U.S., she said.

Costa said low-cost pet vaccination clinics worldwide are prime venues to teach people about rabies because they reach World Rabies Day's target audience.

"We're meeting our benchmark if we're getting rabies prevention information into the hands of the people who need it most," Costa said.

Vaccinating domestic animals is the first line of defense between humans and rabies from wildlife, Tumpey said.

The reserve

Despite reduced supplies of human-use rabies vaccines in the U.S., such vaccines remain more accessible than in some countries with higher infection rates, Costa said.

"So often we say that vaccination is the single most important factor in rabies prevention, but the education is something that can be provided regardless," Costa said. "You know, the education is the most important factor throughout the world, and it's something that we can implement immediately."

Health authorities would like to guarantee production problems won't determine whether vaccine is readily available in the U.S. An ideal vaccine reserve would be maintained by manufacturers and funded by the U.S. government, Dr. Rupprecht said.

"The constraints of where and how funds would be created to manage this portfolio would be the telling issue," Dr. Rupprecht said.