1 May News

Update on the Spread of Avian Influenza

(Clinical Infectious Diseases [Donald Kaye])—Since the H5N1 outbreak began in humans in December 2003 and as of 14 March 2006, the disease has been recognized in birds (mainly poultry) in an increasing number of countries, now totaling over 35. Although starting in the Far East, the infection has been detected in other parts of Asia, Europe, and Africa. Some of the countries reporting at least 1 isolate of H5N1 are Albania, Austria, Azerbaijan, Cambodia, Bulgaria, Cameroon, China, Croatia, Egypt, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Iran, Iraq, Italy, Japan, Kazakhstan, Korea, Malaysia, Mongolia, Myanmar, Niger, Nigeria, Poland, Romania, Russia, Serbia and Montenegro, Slovakia, Slovenia, Sweden, Switzerland, Thailand, Turkey, Ukraine, and Vietnam.

In some countries, isolates have been reported only in migrating birds.

There have been at least 180 cases of documented avian influenza, with at least 101 deaths, mainly among children and young adults. Deaths and cases of illness in humans have been reported in Azerbaijan (3 deaths and 3 cases), Cambodia (4 deaths and 4 cases), China (10 deaths and 15 cases), Indonesia (22 deaths and 29 cases), Iraq (2 deaths and 2 cases), Thailand (14 deaths and 22 cases), Turkey (4 deaths and 12 cases), and Vietnam (42 deaths and 93 cases).

There is concern that, over the next few months, migrating birds from Asia will carry H5N1 to Alaska and subsequently down the West coast of the United States.

To put things into perspective, it is important to remember that virtually all human cases have occurred in people with close contact with backyard poultry. The organized poultry industry immediately culls herds that become infected. Even if infected wild birds are in the United States, there is little danger of major spread to people. The danger is that somewhere along the line, most likely in the Far East (where millions of backyard poultry birds are in close contact with millions of people and where occasionally people become infected), a mutation may occur that will allow easy transmission of virus from person to person.

U.S. Buys 14 Million Courses of Bird Flu Treatments

1 March 2006 (Reuters)—US health officials said they have purchased 114 million courses of antiviral treatments from Roche Holding and GlaxoSmithKline in preparation for a possible avian flu pandemic among humans.

The Department of Health and Human Services ordered 12.4 million courses of Roche's Tamiflu and 1.75 million courses of GlaxoSmithKline's Relenza, it said in a statement.

The agency has already purchased 5.5 million courses of antiviral drugs for its government stockpile, it added. Roche, in a separate statement, said it had filled all previous US orders.

Under the Bush administration's plan, the agency aims to have enough medication to treat 25% of the US population in the event of an outbreak.

Last month, Roche officials said federal officials had agreed to buy 46 million rounds of its treatment.

Experts consider Tamiflu their main choice, but its effects against the virus are not well known, and it must be given early on in the infection.

Relenza, invented by Australia's Biota Holdings and also known as zanamivir, is considered to be equally effective but must be inhaled and may worsen asthma and related conditions.

U.S. Aims to Speed Influenza Vaccine Development

2 March 2006 (Reuters Health [Lisa Richwine])—US health officials issued guidelines to speed development of new vaccines to fight seasonal influenza as well as a feared avian flu pandemic that could circle the globe quickly.

The recommendations aim to encourage more companies to develop flu vaccines and to use new technologies that could shorten the time it takes to make vaccines once a new flu strain is identified, officials said.

The guidelines from the Food and Drug Administration (FDA) should provide “faster time frames, greater certainty, and lower costs” for manufacturers, said Dr. Janet Woodcock, FDA Deputy Commissioner for operations. In part, they outline what types of data the agency needs before approving new vaccines.

Flu vaccine is difficult to make using the current manufacturing process. The flu virus needs to be grown in special types of chicken eggs for months, and the United States has experienced periodic shortages in recent years.

Some companies are working on vaccines using new technologies involving cell cultures instead of eggs and using advanced genetic techniques to formulate the vaccines.

Both would be quicker and more reliable than current methods.

The new guidelines “help clarify what are the fast pathways to get there,” said Dr. Jesse Goodman, Director of the FDA's Center for Biologics Evaluation and Research.

For example, manufacturers may be able to win approval for a pandemic flu vaccine by changing the strain in an already approved seasonal flu shot. That process is simpler than the usual path for an entirely new vaccine, officials said.

The FDA also will consider new vaccines under “accelerated approval” rules that provide a faster route to market for important new products. Those rules “can take 1 to 2 years off time of development and licensure of a product,” Goodman said.

Companies also can test technology that will allow smaller amounts of flu vaccine to be used while still producing enough immunity to fight off an infection, Goodman said.

The FDA will take public comments on the guidelines for 90 days before finalizing them.

Varicella Zoster Immune Globulin Available for Postexposure Prophylaxis

3 March 2006 (Reuters Health)—Varicella zoster immune globulin is now available as VariZIG under an investigational new drug application submitted to the US Food and Drug Administration (FDA) for patients who have been exposed to varicella and are at increased risk for severe disease and complications.

Eligible individuals include immunocompromised patients, neonates whose mothers have signs and symptoms of varicella from 5 days before to 2 days after delivery, premature infants born at 128 weeks of gestation who are exposed during the neonatal period and whose mothers do not have evidence of immunity, premature infants born >28 weeks of gestation or who weigh <1000 g at birth, and pregnant women.

VariZIG should be administered within 96 h after exposure as an intramuscular injection at doses between 125 to 625 U per 10 kg of body weight.

The Centers for Disease Control and Prevention advise that patients be observed closely for signs or symptoms of varicella for 28 days after exposure, with antiviral therapy administered if disease occurs. Five months later, varicella vaccine should be given if it is not contraindicated.

If VariZIG will not be available within 96 h after exposure, physicians should consider using intravenous immune globulin, which should also be started within 96 h.

Providers can acquire VariZIG by calling FFF Enterprises at (800) 843–7477.

Downloadable release forms are available online at http://www.fffenterprises.com. The drug will be shipped with release forms, protocol, an informed consent form, case report forms, an investigator brochure, and drug accountability forms.

Source: MMWR Morb Mortal Wkly Rep 2006; 55:209–10.

Editor's comment. This will replace the previous source of the only US- licensed supply of varicella zoster immune globulin (VZIG) (Massachusetts Public Health Biologic Laboratories), the manufacturer of which has discontinued production of VZIG. The investigational (not licensed) VZIG product, VariZIG (Cangene Corporation) became available under an investigational new drug application submitted to the FDA.

U.S. FDA Advisers Back New Use of Cubist Antibiotic

7 March 2006 (Reuters Health [Susan Heavey])—A US advisory panel supported Cubist Pharmaceuticals' bid to market its Cubicin antibiotic to treat a wider range of staphylococcal infections, citing a need for new agents to target the increasingly drug-resistant bacteria.

The panel of outside advisers to the Food and Drug Administration (FDA) unanimously recommended Cubicin, an injected cyclic lipopeptide, as safe and effective to treat bloodstream infections and narrowly backed the drug to treat infective endocarditis.

Cubicin is already indicated for complicated skin infections. The FDA usually follows the advice of its advisory panels and is expected to rule by 24 March.

“It appears there's a general consensus” regarding the general bloodstream use, said panel Chairman Dr. James Leggett, an associate professor of medicine at the Oregon Health Sciences University in Portland.

But 4 of the 9 experts said there was not enough information to decide whether the drug was suitable to treat endocarditis.

Erratum

The 1 March 2006 issue of Clinical Infectious Diseases included a Reuters Health news story titled “Kids', Teens' Immunization Schedule Updated.” The story incorrectly stated that influenza vaccination is now recommended for infants <6 months old. The story should have stated that the recommendation is for infants ≤6 months old.