Clinicians' biosecurity network report, may 26, 2006

Clinicians' Biosecurity Network Report, May 26, 2006
Published by the Center for Biosecurity of UPMC to present analysis of recent events in biosecurity for healthcare providers
Avian Influenza Update: New Cluster of Human Victims in Sumatra; WHO
Releases Guidelines for Treatment and Prophylaxis of Avian Influenza
By Eric Toner, M.D. and Luciana Borio, M.D., May 26, 2006

Cluster of 8 Family Members in Sumatra Infected with H5N1
On May 23, the World Health Organization (WHO) acknowledged the likelihood that a large cluster of human cases of H5N1 infections
in the northern portion of the Indonesian island of Sumatra is due to human to human transmission [1]. The cluster comprises 8
individuals of one extended family. On April 27, a 38 year old woman became ill, and then died on May 4. While she was never tested
for H5N1 infection, 7 members of her extended family--3 adult siblings, 2 adolescent sons, a 10 year old nephew and an 18 month old
niece--subsequently became ill with WHO-confirmed H5N1 infections, and 6 of the 7 have died. The source of the woman’s infection
is not known. Three of the infected family members shared a room with her on the night of April 29 while she was actively sick and
coughing. The other family members lived nearby. While each of the 7 confirmed cases had prolonged and close contact with an
actively sick individual, it appears that they may not have had close contact with the index case, raising the possibility of more than
one generation of transmission. No one outside the family has become ill, and only blood relatives (i.e. not spouses or in-laws) have
been involved.
Full sequence analysis of 2 viral specimens from this cluster shows no evidence of reassortment or of known mutations thought to
increase the likelihood of human to human transmission. In addition, the sequences appear to be similar to those of birds from the
region last year. Live virus has not been found in the area, and there have been no reported outbreaks in animals, although
serological studies have found evidence of H5 antibodies in pigs, chickens and ducks nearby. It is reported, however, that farmers in
the area have not been cooperating with efforts to test their animals [2].
While many other family clusters of H5N1 have been reported, this is the largest. In addition, while several previous clusters have
been thought to indicate limited human to human transmission, this is the first instance in which more than one generation of
transmission is considered likely. The fact that only blood relatives are involved has also been noted, and has been observed in all
previous clusters of human H5N1 infection as well, leading some experts, including Dr. Robert Webster, to speculate that this may be
evidence of a genetic susceptibility to the infection [3].
WHO Releases Guideline for Treatment and Prophylaxis of Avian Influenza
The WHO has just issued guidelines for the treatment and prophylaxis of avian influenza A (H5N1) virus infection [4], and stated that with the H5N1 virus now confirmed in birds in more than 50 countries, additional sporadic human cases should be anticipated. The guidelines were formulated by an international panel of experts that included clinicians with experience in treating H5N1 infected patients. The panel considered the benefits, harms, burdens and cost of interventions. The WHO’s evidence-based guidelines classify recommendations as strong or weak, characterize the quality of the evidence as high, moderate, low and very low, and are specific to the current pre-pandemic conditions. It is important to note that there are no available data from controlled clinical trials of treatment or prophylaxis for H5N1 infection, and most evidence was formulated from data gathered from small observational case series, animal studies, and extrapolation of treatment and chemoprophylaxis data derived from seasonal influenza cases. While these guidelines are an important contribution, clinical data to establish the optimal treatment regimen for infected patients are urgently needed.
Table 1: Key recommendations for the treatment of patients in which H5N1 infection has been confirmed or is strongly

Availability of Therapy
M2 inhibitor (amantadine, rimantadine) might be added to neuraminidase inhibitor if local surveillance data shows virus susceptibility Although animal studies have indicated that a prolonged course of high-dose oseltamivir increases survival [5], the WHO guidelines recommend treating H5N1 infected patients with the same regimen used for the treatment of seasonal influenza. With regard to geographic susceptibility of M2 inhibitors, clade 1 H5N1 virus isolated from humans in Thailand carries mutations associated with resistance to M2 inhibitors, whereas, to date, clade 2 virus isolated from China does not seem to carry these mutations.
Table 2: Key recommendations for chemoprophylaxis of patients potentially exposed to H5N1
Availability of
Risk Exposure Category
Moderate: prophylaxis might be administered Notes: 1.) M2 inhibitors (amantadine or rimantadine) should not be administered as prophylaxis in pregnant women.
2.) Amantadine should not be administered as prophylaxis to the elderly, to individuals with renal insufficiency, or to persons who are
taking neuropsychiatric medications or who have neuropsychiatric or seizure disorders.
Table 3: Risk Exposure Categories
> Individuals who handle sick animals > Household or family members in proper personal protective equipment infected patient.
> Those who have donned proper PPE during exposure > Those involved with general culling > Health care or laboratory personnel samples in the absence of proper PPE.
Recommendations for other Treatments
The panel does not recommend the use of corticosteroids, interferon alpha, immunoglobulin therapy, or ribavirin unless evaluation of
these treatments is undertaken under the auspices of a randomized, controlled clinical trial. Antibiotics should be administered only if
clinically indicated for the treatment of bacterial pneumonia, but not for the general prevention of secondary bacterial pneumonia
This week’s developments are worrisome. Press reports [6] indicate that in Sumatra, residents of the affected village have
demonstrated fear of and hostility toward authorities. It has also been reported that one the infected persons who died refused to take
oseltamivir. Such developments suggest that the effective implementation of public health guidelines may prove as challenging as the
disease itself.
1. World Health Organization. Avian influenza – situation in Indonesia – update 14. Available at
essed May 24, 2006.
2. Tan Ee Lyn. Indonesia's bird flu fight riddled with problems. Reuters, 23 May 2006. Available at
essed May 24, 2006.
3. Jason Gale. Human Genetics May Play a Role in Avian Flu Cases. Bloomberg, May 11, 2006. Available at
Accessed May 25, 2006.
4. World Health Organization. WHO Rapid Advice Guidelines on pharmacological management of humans infected with avian
influenza A (Hy 25,
5. Yen HL, Monto AS, Webster RG, Govorkova EA. Virulence may determine the necessary duration and dosage of oseltamivir
treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis 2005;192(4):665-72.
6. Helen Branswell. Indonesian bird flu cluster may be human-to-human-to-human spread. Canadian Press, May 23, 20.
Accessed May 25, 2006.
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