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Pandemic ‘dry run’ is cause for concern

Naturevolume 441pages554555 (2006) | Download Citation

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Indonesian bird-flu cluster rings alarm bells.

A cluster of avian flu cases in Indonesia last month is being seen by many experts as a dry run for the handling of an emerging pandemic virus. But although the World Health Organization (WHO) says that all went well, some critics allege that the response to the virus — thought to have been moving between humans — shows how ill-prepared the international community and affected nations still are.

“If this was a test to see whether Indonesia could contain a virus, they failed miserably.”

“Any chance of containment was absolutely hopeless,” says Andrew Jeremijenko, who until March was head of influenza surveillance at the US Naval Medical Research Unit 2 in Jakarta. “If this was a test to see whether Indonesia could contain a virus, then they just failed miserably.”

The difficulties encountered also raise questions as to the practicality of a plan to try to stop an emerging pandemic in its tracks by rapid intervention. Modelling studies predict that if a pandemic virus emerges, the WHO would have at most three weeks to help the affected country to quarantine all carriers and treat those infected with antivirals (N. M. Ferguson et al. Nature 436, 614–615; 2005).

The first case in the cluster fell ill on 24 April and died on 4 May. Samples were not taken, however, and alarm bells only rang when her relatives started going to hospitals in the days that followed. In total, eight members of an extended family in the village of Kubu Sembelang in north Sumatra became infected with H5N1. Six more of them have since died.

Jeremijenko says the response was slow and disorganized. The first WHO official and a team of local officials didn't reach the village until 12 May. Other international experts did not reach the village until the following week, at least in one case because of difficulties getting an invitation from Indonesia's ministry of health, according to Jeremijenko. Villagers also refused to cooperate with the team initially. Several of the H5N1 patients fled hospitals, returning coughing to the community.

Spreading the news

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.

Johannes Ginting is thought to have caught bird flu from a relative. Seven members of his family have died. Credit: AP PHOTO/BINSAR BAKKARA

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.

Concerns over the cluster itself have eased as no new cases have since been reported nearby, and the WHO says the virus's sequence shows “no evidence of significant mutations”. The sequences have not been made public yet. The all-clear will not be given for another two weeks or so, however, and the pharmaceutical company Roche has been put on standby to send antiviral drugs to the region.

Teams on the ground are trying to monitor fresh cases. But thousands of Indonesians die every day from tuberculosis, dengue and other infectious diseases, and almost all go untested for H5N1. On 29 May, the WHO announced six more cases in other areas of Indonesia, two of which were also a family cluster.

“There have been a number of family clusters where only one person was tested,” says Jeremijenko, adding that there is “only limited testing, in large cities such as Surabaya, Medan, Bandung and Jakarta. We know we are missing cases, especially in rural areas.”

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.

Another explanation is that the first case in last month's cluster had a particular genetic susceptibility to the virus, making her a ‘superspreader’. But it is too soon and the data are too sparse to know for sure, says Bjorge.

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

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