What We Don't Know

Seven out of eight? That’s the report on the recent family cluster of human H5N1 cases in Kubu Simbelang village, Karo District, North Sumatra, Indonesia. Apparently, an initial case infected seven laboratory-confirmed cases, all members of an extended family. Seven of the eight infected family members have died. (WHO 2006)[1] Is this how deadly this virus can get? How much do we know about this property of H5N1?

According to the World Health Organization (WHO) [2], as of May 29, 2006, there were 224 confirmed cases of human H5N1 avian influenza, and among those there were 127 deaths.

Country	2003		2004		2005		2006		Total
	cases	deaths	cases	deaths	cases	deaths	cases	deaths	cases	deaths
Azerbaijan	0	0	0	0	0	0	8	5	8	5
Cambodia	0	0	0	0	4	4	2	2	6	6
China	0	0	0	0	8	5	10	7	18	12
Djibouti	0	0	0	0	0	0	1	0	1	0
Egypt	0	0	0	0	0	0	14	6	14	6
Indonesia	0	0	0	0	17	11	31	25	48	36
Iraq	0	0	0	0	0	0	2	2	2	2
Thailand	0	0	17	12	5	2	0	0	22	14
Turkey	0	0	0	0	0	0	12	4	12	4
Viet Nam	3	3	29	20	61	19	0	0	93	42
Total	3	3	46	32	95	41	74	48	224	127

If one believes these counts, they suggest that a person who is diagnosed with an H5N1 infection is more likely to die than survive. The ratio of deaths to diagnosed cases is a measure of how deadly an infectious agent is. Customarily, this ratio is called case-fatality rate. As taken from the May 29 data, the case-fatality rate for H5N1 infections since 2003 is 127/224 = 0.57, or 57%.

We don’t know the true number of H5N1 cases

A case-fatality rate of more than 50% is extraordinarily high for an influenza virus strain. Given that most persons were infected in areas with poor or absent systems of public health and medical care, it is quite possible that only the most conspicuously severe cases of H5N1 infection were counted and that many more -- but milder -- cases went unreported.

Let’s play with the numbers. Given the same number of deaths, but twice as many infected persons, let’s say that half of them were not diagnosed and thus not counted, the case-fatality rate would drop to 127/448 = 0.28, or 28%. With 20 times as many cases and the same number of deaths, the case-fatality rate would be roughly 2.8%, which is similar to that of the 1918 pandemic and a bit less scary. We can be rather sure that there were undetected cases, but we don’t know how many, or how many of those died.

What evidence do we have?

The most likely place to test to determine if there are indeed many milder -- and undetected -- cases would be among persons with contacts to known cases. Several studies are under way to test for antibodies among contact persons. Unfortunately, some results are kept from the public, and the published data are inconclusive. So far, such studies have failed to identify mild or asymptomatic cases (Writing Committee 2005)[3], which suggests that there probably are very few undetected cases. (Enserink 2006)[4] 

We don’t know the true number of H5N1 deaths

Could it also be that the reported case-fatality rates underestimate the true one? Even if there are few undetected infected persons, could it be that deaths that are caused by H5N1 are never properly attributed to the virus? If so, the H5N1 case-fatality rate might be even higher than 57%. (Butler 2006)[5] Perhaps over 80%, as in the recent Indonesian cluster? At this point, let’s remember quickly that extremely few persons became infected, and that this infection is quite hard to get.

What if?

Apparently, there have not been any H5N1 cases in the Indonesian cluster since May 22, and the virus remains very hard to catch. Perhaps the mutation of the virus that was isolated in the cluster was “insignificant,” as claimed by WHO. But what if? Some scientists and commentators argue that an H5N1 strain that managed to move more easily among humans would also be less deadly. This would probably be true, but we don’t know that either.

---

[1] WHO

Avian influenza – situation in Indonesia – update 16

31 May 2006; http://www.who.int/csr/don/2006_05_31/en/

[2] http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_03_06/en/index.html

[3] Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5, Beigel et al.

Avian influenza A (H5N1) infection in humans.

N Engl J Med. 2005 Sep 29;353(13):1374-85.

[4] Enserink M.

Avian influenza. Amid mayhem in Turkey, experts see new chances for research.

Science. 2006 Jan 20;311(5759):314-5.

[5] Butler D.

Pandemic 'dry run' is cause for concern. Indonesian bird-flu cluster rings alarm bells.

Nature 1 June 2006;441(7093):554-555.

doi:10.1038/441554a; Published online 31 May 2006

Comments

[Renate]

In regards to the Avian Flu , I have a strong belief that this supposed flu is being given too much press and incites fear in the populace. Avian flu casualties that have been infected have been dealing with infected birds. This rarely happens in developed countries as our health system is more advanced in screening. There also has been no evidence that the flu can mutate across the human-bird barrier and therefore be spread between humans. I wish we were given all the facts instead of being given only a little information. This causes fear and panic in less well read persons, which sets up a vicious circle.

I hope in future these types of alarmist tactics were repudiated by scientists and not left to the imaginations of the uninformed. It is as bad as the "terrorist threats," Y2K and a host of other supposed dangers. Eventually society "burns out" under constant attack and when this happens and a real pandemic occurs, society just sees it as another"crying wolf syndrome."

Renate Van Dorsser
Edmonton, Canada

[Jody]

Interestingly, W.H.O. announced yesterday that 4 health workers in the Karo cluster that contracted flu like illness did not have H5N1, despite the fact that serology will take at least 15 to 21 days to establish that fact. What do you think the chances are that 4 persons who were exposed to H5N1 carriers and then became ill themselves within the incubation time frame are not infected? Fi shame on W.H.O. for lying!

[Jody]

P.S. The latest issue of Nature states that the Karo H5N1 virus is found in the nose and throat--signifying a change in the cells the virus attacks. Sounds like a significant mutation to me! Note that the fatality rate remains at 80% with that change, too, not dropping as everyone is hoping.

[Jody]

As to the false belief that bird flu is not transmitting human to human, might I refer all interested readers to W.H.O updates in the last two weeks. They now acknowledge at least 6 clusters where human to human transmission is the only explanation that they cannot discount. In actuality, the number of clusters is much higher due to the non-sampling of family members that died prior to tested patients. Efficient and sustainable transmission between people has just taken a leap with the disease now found in the nose and throat.

Should we be worried? I think so. I lived through the SARS crisis, and I saw no better cooperation in Canadian citizens than I read about in Indonesia, as relates to self-quarantine.

W.H.O. is busy re-writing the pandemic phases, and are going to eliminate phases 4 & 5. So we will go from phase 3 where we are now, straight to the pandemic. Isn't that fun?

[rachel]

I have been hearing about the bird flu for about 3 years now. I have to admit though that I have never been as afraid as I am now since I became a mom to a beautiful boy who now is 2. The health of my son is my top priority and to think that the world most likely faces deadly pandanemic and on top of that not being prepared scares me half to death, so I guess we should pray for a miracle since it seems this is the only thing that's gonna get us out of this one.

[Jody]

There is good evidence that a vaccine that contains key pieces of H5N1 virus could already be made. There is reason to believe that segments like PB2 E627K (which have been theorized to allow the virus to replicate at lower temperatures like in the human throat) and are found in all Qinghai HA could be included. Although complete protection from infection could not be guaranteed, this vaccine would hopefully prevent the fatality rates we are seeing. Where is the political will? There is more to do than "pray"! 2000 dead eider ducks were discovered in a breeding colony in Nunavut, and arm- chair scientists declared it to be "one heck of an outbreak of avian cholera". No one has tested any dead birds......

Thailand declared one third of its country a disaster zone yesterday due to bird flu....2 weeks ago they said they had none!Last week, they had 3100 people in quarantine, two human deaths.