Declan Butler, reporter

May 31, 2006

Breaking the silence: “If this was a test to see whether Indonesia could contain a virus, they failed miserably”

Filed under: avian influenza — admin @ 10:10 pm

The latter quote is from a front-page article I’ve published in Nature tonight on what the experience of the large human cluster of avian flu cases in Indonesia says about the realities of attempting to slow the spread of, much less extinguishing at source, an emerging pandemic in the context of a developing country, with poor health infrastructure.

Plans
by the World Health Organization (WHO) to try to slow or contain a pandemic show that to have any hope of success these would require rapid and decisive action within at most a three-week window from the emergence of a pandemic virus. But the handling of the cluster in Indonesia, as described in the article, is one of delays and confusion. Brief recap; this involved 8 members of an extended family in Kubu Sembelang, 7 of whom died, a patient fatality rate seen nowhere else.

WHO will no doubt argue that it reacted fast; it got samples on 10 May, results of viral testing on the 11th, and had one man, alongside local health teams, at the scene of the outbreak on the 12th. But that was already 19 days after the initial case fell ill, 16 days after she went to hospital, and more than a week after she died.

Meanwhile, villagers concerned that their animals would be killed became hostile to outsiders, resulting in international experts and local teams being subsequently barred from the village for a whole five days. Victims refused to take Tamiflu, fled the government hospital, while families refused protective gear when caring for their sick… the list of unanticipated confusion goes on.

The initial quote came from Andrew Jeremijenko, who until March was head of influenza surveillance at the US Naval Medical Research Unit 2 in Jakarta (NAMRU-2), and I’d like to thank him for having the courage to speak out in my article.

Andrew, who spent last weekend treating wounded at the scene of the Indonesian earthquake — he was also involved in the tsunami response (see article here) — explained his reasons to me in an email: “I think it is our duty to point out that containment has serious limitations, and in an unusual event like this people need to be more aggressive then usual. Political deference though acceptable in some circumstances in others is not. I think this is important information to get out there.”

Working at NAMRU-2, Andrew witnessed the enormous gap between the official rhetoric and the reality on the ground. Take the recent declaration by Michael Leavitt, US Secretary of Health and Human Services’ statement to the World Health Assembly: “In closing, I ask this Assembly today to pledge with me to abide by four principles of pandemic preparedness:

* Transparency,
* Rapid reporting,
* Data sharing and,
* Scientific cooperation.

In reality of course, for many political and cultural reasons — including those of the scientific community itself — although some progress is being made, lip service is often paid to these on the ground, and that includes the US’s own CDC — see Flu researchers slam US agency for hoarding data. The problem, as we pointed out over a year ago in Nature — see “On a wing and a prayer” — is this:

“Each human case that occurs in Asia is potentially a global threat. The international virology community needs to be permanently there, on the ground. We need to diagnose cases swiftly, and treat the patients and all their contacts immediately with antiviral drugs to try to kill the pandemic at source.

To understand the genetics, and link this to the epidemiology and pathology of the virus, we need immediate sharing of all virus samples and data. None of this is happening adequately. National governments’ performance is half-hearted, incomplete and far too slow. International organizations are working with their hands tied behind their backs, for bureaucratic and diplomatic reasons. In short, the level of current efforts is not commensurate with the threat we face.”

That remains the elephant in the room. The WHO, like FAO and OIE, answers to its member states — not the other way round, as many seem to think — and therefore it is almost taboo for its officials to criticize the actions of a member state, if they want to enjoy any cooperation on the ground. They deserve to have their hands strengthened, as noted in the recent Nature editorial, Dreams of flu data.

“Not before time, the WHO will have broader powers in 2007, when international health regulations, agreed by its members in May last year, come into force. These impose obligations on states to respond to any infectious disease of international concern. Cat-and-mouse games will no doubt continue, but the WHO will at least have a ‘health policing’ role, something that it currently lacks.”

But with the exception of a few reporters, notably Helen Branswell at Canadian Press, Maggie Fox at Reuters, and Nick Zamiska at the Wall Street Journal, many journalists simply regurgitate the parsimonious information from the PR departments of such agencies as if it were gospel.

The critical tone of my article tonight, should in no way be interpreted as disparaging of the valiant efforts of the many committed staff and doctors in Indonesia and within the WHO battling the problem on the ground. But we also must be aware, as journalists, and citizens, that politics complicated matters.

And last, let’s touch on the interesting question of sharing sequence data — see again Dreams of flu data. The sequences of virus from the victims of the Indonesia cluster have not been made public. Why not? In the article, there is much buck passing among the three actors involved.

1.”Malik Peiris, a virologist, doing a great honest job at the University of Hong Kong who sequenced the virus, declined to comment on any mutations, saying that making sequences public is not his call. “Our job as a WHO reference lab is to report back to the originating country and the WHO,” he says.”

2.”The WHO also declined to give any details. “We will leave that to the government of Indonesia, the owner of the data,” says Bjorge.”

3. In an email received from the Indonesian government after my deadline, it states with respect to making data public: “We are fully aware of the threat of the next influenza pandemic. And Indonesia is fully supporting whatever measures are considered necessary to prevent, control and contain a potential pandemic. ;”

So apparently, noone is opposed to depositing the sequences in Genbank immediately, but noone is taking the decision to do so. In the Nature editorial, “Dreams of flu data” we argued: “Genetic data are also lacking. When samples are sequenced, the results are usually either restricted by governments or kept private to an old-boy network of researchers linked to the WHO, the US Centers for Disease Control and Prevention, and the FAO. This is a far cry from the Human Genome Project, in which all the data were placed in the public domain 24 hours after sequencing. Many scientists and organizations are also hoarding sequence data, often for years, so they can be the first to publish in academic journals. With the world facing a possible pandemic, such practices are wholly unacceptable. Nature and its associated journals are not alone in supporting the rapid prior exposure of data when there are acute public-health necessities. ”

Three cheers, then, to Ilaria Capua of the Tri-Veneto Region Experimental Animal Health Care Institute in Italy, who last month threw down the gauntlet to her colleagues by refusing to put her latest data on Nigeria and Italy in these private networks. Instead she uploaded them to GenBank and called on her colleagues worldwide to do likewise. Only in this way can researchers establish and track the global pattern of the evolution of the bird-flu virus.”

Is it perhaps time for the Human Genome Project’s “Bermuda Agreement” on sequence deposition to be applied to all H5N1 sequences?

Below are a few excerpts from my article tonight.

“The WHO made the outbreak public on 18May. Health officials — and stock markets — worldwide trembled five days later when the WHO budged from its previous standard line that “the most plausible source” of the cluster was infected poultry, and acknowledged for the first time since the emergence of H5N1 that an extended chain of human transmission was the most likely explanation.

Steven Bjorge, a WHO official in Jakarta, disputes the allegation of unnecessary delays and bungling, arguing that the WHO and the Indonesian government reacted promptly. “The team was in the field early, and the Indonesians are doing a good job,” he says. The abscondments from hospital were “an unusual experience”, he adds.”

And some discussion of possible explanations for the cluster:

“What caused the suspected human-to-human transmission at Kubu Sembelang is still a mystery. Nature has learned that the cases differed from past Indonesia cases, in that they had much higher viral loads in the throat and nose. Human-to-human transmission is more likely through droplets coughed from the nose and throat than from infections further down the respiratory tract.

Mutations in cases in Turkey earlier this year showed a substitution of glutamic acid with lycine at position 627 in the PB2 component of the polymerase gene. The mutation is thought to allow the virus to survive in the cooler nasal regions. This mutation has not been publicly reported in Indonesia previously, but Nature has learned that it occurred in at least one case in August 2005.”

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