The information was kindly provided by Dr.Akira Goto to ProMed Mail. The information was translated into English by Dr. Akira Goto from the Ministry of Health, Labour and Welfare of Japan website.Please note that this is merely a digest of the information, and
may contain translation errors.

Source: http://www.mhlw.go.jp/topics/bukyoku/kenkou/tori/041222/1.html

Japan: Human Cases of Avian Influenza - Laboratory Findings
--------------------------------------------------
In response to the posting "Avian influenza, humans - Japan (Kyoto)(03):
conf" (archive number: 20041222.3372), I would like to forward some
information from the website of the Ministry of Health, Labour and Welfare
of Japan. Please note that this is merely a digest of the information, and
may contain translation errors.

Subjects of the survey:
----------------------
"exposed groups"

[A] (farm workers): 16 workers at the chicken farm where the outbreak occurred
[B] (local government employees): 42 local government employees who were
involved in controlling the outbreak (investigating the farm and/or culling
the chickens during the event)

"control group"
[C]: 33 local government employees who did NOT participate in the control
operation

Blood samples:
-------------
Blood samples were drawn 19-28 Apr 2004, about one month after the end of
the outbreak control operation. In addition, 4 people among the 58
"exposed" had their blood taken on 11 Mar 2004, and those samples were also
tested in this survey.

Antibody assay:
---------------
Neutralizing antibody titers against the influenza A(H5N1) Kyoto strain
(A/Chicken/Kyoto/3/2004) were measured using a "micro-neutralizing assay"
at the Department of Virology III of the National Institute of Infectious
Diseases.

Results of the assay:

Neutralizing antibody titer

Group / Number / <1:10 / 1:10 or higher /

[A] /  16 /  12 /  4* /
[B] / 42 /  41 / 1 /
[C] / 33 / 33 / 0 /

*note: serum pair showed "seroconversion" in one of the 4; "seropositive"
farm workers; no serum pairs were available for the other 4 "seropositive"
people in groups [A] and [B].

(1:10, which is the lower detection limit of this micro-neutralizing assay,
was chosen as the cut-off value, because all 33 of the members of the
control group showed titers of less than 1:10.)

Symptoms of the 5 people who showed "positive" antibody titers:
--------------------------------------------------
One farm worker, who exhibited seroconversion, had a sore throat for
several days just after participating in the operation. However, this
person did not develop fever or other systemic symptoms.  4 other people
also failed to show systemic flu-like symptoms such as fever.

commentary by Dr. Henry Niman

Although five workers had antibody against A/chicken/Kyoto/3/2004(H5N1), a titer of >10 is not a very convincing number, (patients exposed to the 1918 pandemic virus had higher titers 85 years after exposure) and indeed only 1 of the 5 workers was tested twice to show a rising titer.

Since the positives were involved in decontaminating an H5N1 infected farm over an extended time period, the titer may in fact represent antibody to killed virus, since no virus was isolated from any of the "infected" workers.

However, even if the workers were infected with A/chicken/Kyoto/3/2004(H5N1) or a closely related virus, the failure of the virus to produce serious illness in these workers would not indicate that "exposure to influenza virus-infected poultry does not pose a serious risk to human health".

The H5N1 isolates in Vietnam and Thailand are associated with a case fatality rate in excess of 70%.  Although the sequences of the isolates from Japan have not been made public, full sequences from a large number of 2004 H5N1 isolates in Thailand and Vietnam have been published and these isolates (from humans, wild cats, and a variety of wild and domestic poultry) have polymorphisms specific for Vietnam, Thailand, or both countries.  Many of the polymorphisms are not found in other H5N1 isolates, but in fact are found in mammalian isolates, most notably H1N2 (need serious attention).

The above Kyoto virus is described in a MAFF report dated 6/30/2004.  The table on page 26 appears to show the homology between a representative Kyoto isolate and a number of other H5N1 isolates (Ck/Korea/ES/03, Dk/China/E319-2/03, Dk/Anyang/AVL-1/01, Thailand/KAN-1/04, Ck/Supanburi/2/04, Dk/Angthong/72/04,  Qa/Angthong/72/04, Vietnam/1096/04, HK/213/03, Ck/HK/YU562/01, HK/156/97).

All 8 genes are listed and a full data set is listed for most isolates.  The isolate from Korea is 99% homologous for all 8 genes.  The percent homology is considerably lower for other isolated.  For HA and NA of the Thailand and Vietnam isolates, the percent homology is 96% and 97% respectively for HA and NA.  Thus, there are considerable differences between the isolates from Japan and the isolates from Vietnam or Thailand (the data of recent H5N1 isolates in China will be of great importance).

Extrapolating weak antibody data from a small number of farm workers with repeated exposure to killed virus to exposure to avian influenza infected poultry is not justified because of the publicly available sequence and case fatality data from Vietnam and Thailand H5N1 infected people and animals.