24 August 2005
WHO to receive 3 million treatment courses (30 million capsules) of the only oral anti-H5N1 drug (oseltamivir) by mid-2006 as outbreaks spread to Kazakhstan, Russia and Tibet.
Today the WHO announced that the manufacturer (Roche) of the only oral drug (oseltamivir) active against the H5N1 influenza virus will donate 3 million treatment courses (at 10 capsules/course a total of 30 million capsules) beginning in early 2006 and ending by mid-2006.
The Director-General of the WHO, Dr. LEE Jong-wook, signed the agreement with Roche and noted in a media briefing that “New outbreaks have recently been confirmed in birds in Kazakhstan, Mongolia, and the Russia Federation…An influenza pandemic will not discriminate between those who live in mansions and those who live in slums”.
Modeling use of antiviral medications to attempt to control an H5N1-like pandemic in Asia two groups (Longini IM et al., in Science Express Aug. 3, and Ferguson N et al. in Nature) recently reported that antiviral stockpiles of oseltamivir such as those being donated next year to the WHO would be needed for rapid delivery and distribution after sustained person-to-person spread began of a pandemic influenza strain.
Of note, a treatment course of oseltamivir is usually considered to require 10 capsules, two given every 12 hours for 5 days. A prophylactic course of oseltamivir given after each exposure to an influenza virus has been defined as also 10 capsules, one given each day for 10 days.
Unfortunately, a person does not always know when they have been exposed to an influenza virus and therefore a longer term (weeks-months) prophylactic course, requiring many more capsules of oseltamivir may be needed. For example a two month prophylactic course, given for repeated H5N1 influenza exposures, would require 60 capsules, taken one each day, rather than 10 capsules.
In addition, a recent study in the Journal of Infectious Diseases involving mice infected with H5N1 suggested that eight days of oseltamivir therapy, rather than 5 days of treatment (not prophylaxis) might improve outcome.
Meanwhile, H5N1 has been found in two locations in western China, Tibet (Lhasa), Kazakhstan, Mongolia, and at least six areas in Russia. Moreover, in the August 5 (Vol 18-No. 31) report on the World Animal Health Organization (“OIE”) website (www.oie.int) additional pigs tested positive by PCR for H5N1 in Indonesia (Panongan subdistrict, Tangerang district, near Jakarta).
Potential spread of H5N1 by migratory birds across the Ural mountains into Europe or to SW Asia, India, or the Middle East is recognized, although one writer (Hon S. Ip, Diagnostic Virology Laboratory in Wisconsin, USA) today questioned the causal role of migratory birds as transmitters of the virus in a ProMEDmail letter titled “Dead birds don’t migrate”.
Progress on human H5N1 vaccines, cited recently from the initial US study using a non-adjuvanted vaccine, different doses of vaccine, and two immunizations is welcome (NY Times front page 7 August). Further testing of new vaccines in multiple nations of the world is still needed, including testing of vaccines that would decrease the amount of H5N1 antigen needed, with the ideal being only one immunization to confer protection and less than or equal to the usual 15ug of influenza antigen per shot use din annual flu vaccines.
Such an “antigen–sparing” vaccine may require use of a vaccine adjuvant (e.g., the FDA-licensed vaccine adjuvant “alum”; on the other hand, researchers announced this week a planned study by Chiron and supported by the US NIH that will use the adjuvant MF-59 with an experimental H9N2 avian influenza vaccine).
Another potential “antigen-sparing” strategy could be alternative routes of immunization (e.g., SQ vs IM), perhaps compared with or without an adjuvant, i.e., proceeding with vaccine studies “in parallel” rather than “in series”.
The need for vaccine safety is paramount, for the sake of each vaccinee, well as from the vaccine regulatory body perspective (e.g., the US FDA). If, however, the next winter brings the first wave of a pandemic influenza “Pacific Storm,” then a safe and effective vaccine will be in extremely high demand worldwide.
Daniel R. Lucey, MD, MPH
Adjunct Professor of Microbiology and Immunology
Georgetown University School of Medicine
Director, Center for Biologic Counterterrorism and Emerging Diseases