25 August = 2005

25=20 August 2005

=93Necessary=20 but Not Sufficient=94: The 3 Million Courses of Oseltamivir for H5N1 = Nascent=20 Pandemic Control. = Five (5)=20 Other Criteria are Required, Similar to the US Cities Readiness = Initiative=20 (CRI).

In=20 the recent publication by Neil =20 Ferguson (from Imperial College London) and colleagues in = Nature=20 titled =93Strategies for containing an emerging influenza pandemic in = Southeast=20 Asia=94 six (6) criteria were listed that had to be achieved to predict = a high=20 probability of = controlling pandemic=20 influenza when it first began to occur. =20 Importantly, only one of these six criteria included having a = rapidly=20 deployable stockpile of at least 3 million courses of the anti-H5N1 oral = drug=20 oseltamivir (=93Tamiflu=94).

Thus,=20 the news announced 24 August that the WHO had received a commitment from = Roche=20 to donate 3 million treatment courses of oseltamivir for use as a = stockpile=20 against pandemic flu should be seen as necessary but not sufficient = because the=20 other five (5) criteria for success must also be = met.

The=20 complete six (6) criteria quoted from the conclusion of the = Nature paper=20 are:

1).=20 =93Rapid identification of the original case = clusters=94

2).=20 =93Rapid, sensitive case detection and delivery of treatment to targeted = groups,=20 preferably within 48 hours of a case arising=94

3).=20 Effective delivery of treatment to a high proportion of the targeted = population,=20 preferably > 90%.

4).=20 Sufficient stockpiles of drug, preferably 3 million or more courses of=20 oseltamivir

5).=20 Population cooperation with the containment strategy and, in particular, = any=20 social distancing measures introduced

6).=20 International cooperation in policy development, epidemic surveillance = and=20 control strategy implementation. = Containment is unlikely if Ro (the average number of secondary = cases for=20 each primary case of a contagious disease) exceeds 1.8 for the new = pandemic=20 strain.=94 =

Understandably,=20 the Ro will not be known at the time it is essential to implement a = containment=20 policy at the start of the pandemic. In addition, it should be = emphasized that=20 this model focuses on a rural outbreak initiating the pandemic, = and=20 recognition of such an outbreak while it is still rural. Specifically, = the=20 authors state in their section on =93Effect of antiviral prophylaxis=94 = that the =91maximum number of oseltamivir courses that would = be needed=20 to control the pandemic in which cases arise in Bangkok at an early = stage of the=20 outbreak can increase by an =93unfeasible order of=20 magnitude=94.

The=20 other five criteria above = deserve=20 even more effort and resources now that the criteria of having 3 million = courses=20 of oseltamivir is being met = (10=20 capsules/course for either one standard treatment course at two = capsules/day,=20 or for a single 10 day = prophylactic=20 course (as per Ferguson et al. in their modeling paper in Nature) = at one=20 capsule/day).

In=20 fact, similarities can be recognized between the six most critical = criteria=20 outlined above in this model to control a nascent influenza pandemic in = rural=20 Asia and the US Cities Readiness Initiative (CRI) (described on the CDC = website=20 at www.bt.cdc.gov/cri/qa.asp) = Both=20 require (1) rapid detection of = the=20 disease, (2) rapid delivery of treatment or prophylaxis preferably = within 48=20 hours, (3) effective delivery to a high proportion of the targeted = population,=20 preferably > 90%, (4) sufficient stockpiles of the needed = antimicrobial drugs=20 e.g., from the Strategic National Stockpile (SNS) in the case of the = CRI), (5)=20 cooperation of the involved population with any Public Health = containment=20 policies, and (6) both national and international cooperation in = epidemic=20 surveillance and policy =20 development. =20

CRI=20 efforts in the USA that began in ~21 cities and metropolitan areas over = the past=20 year to implement distribution of antibiotics within 48 hours e.g., = after an=20 aerosol attack with anthrax, have proven how difficult meeting this 48 = hour=20 criteria would be in one or more US cities. To be able to meet such a 48 = hour=20 criteria for delivering oseltamivir to a large number of persons in = rural Asia=20 is probably no less challenging and would require much multidisciplinary = international preparedness planning.

Daniel=20 R.Lucey, MD, MPH

Adjunct=20 Professor of Microbiology and Immunology

Georgetown=20 University School of Medicine

Director,=20 Center for Biologic Counterterrorism and Emerging = Diseases

Department=20 of Emergency Medicine, Washington Hospital Center

Washington=20 DC

e-mail:=20 Daniel.R.Lucey@Medstar.net=

website:=20 http://www.bepast.org/