Mild H5N1 Cluster in Indonesia Raises Pandemic Concerns

Commentary

Mild H5N1 Cluster in Indonesia Raises Pandemic Concerns
Recombinomics Commentary 13:40
November 24, 2008

Three years ago, a resident of Sinjai regency in South Sulawesi, Khairil Anwar, 22, was identified as positively infected by the virus. Khairil, the first man in Indonesia declared to be infected by the bird flu virus, is still healthy up to now.

The above comment as part of the report on the H5N1 simulation exercise in Makassar in South Sulawesi is curious. Two weeks ago a large cluster was reported in Makassar. Although the first 7 cases tested were H5N1 PCR positive, the patients recovered after prompt treatment with Tamiflu, raising concerns about mild H5N1 cases that are efficiently transmitted.

The first confirmed H5N1 case in Indonesia was a government worker who died in Tangerang 3 1/2 years ago, along with two of his daughter. The index case tested positive for H5 antibodies twice, which was confirmed by WHO regional labs in Atlanta (CDC) and Hong Kong. However, since the samples were collected three days apart the high titer of 320 had doubled to 640, but fell short of the WHO requirement of a four fold increase. Her sister also died with bird flu symptoms, but was not test. Her father was PCR positive and H5N1 was subsequently isolated. That isolate became the vaccine target for clade 2.1, but use of that isolate led to an Indonesian ban on shipment of samples to NAMRU-2 in Jakarta, as well as collaborating labs in Atlanta and Hong Kong.

Similarly, information on H5N1 outbreaks in Indonesia was diminished. After Indonesia declared H5N1 endemic in 2006, they stopped submitting reports on H5N1 outbreaks in poultry. Recent media reports suggest that 50% of poultry sold in the Jakarta area is now H5N1 positive. Moreover, bird samples that were being tested by the WHO regional site in Australia was also stopped.

On the human side, sequences were withheld and then a news blackout was imposed after several H5N1 cases were linked to relatives who had also died with bird flu symptoms, but had been misdiagnosed as have lung inflammation, dengue fever, or typhus. More recently, lab confirmed cases in Semarang and Sulawesi were denied by the Ministry of Health without explanation for the death or hospitalizations. The cases included a cluster of 17 patients who were hospitalized over a 48 hour time period, raising concerns of increased transmission efficiencies.

An increase in transmission frequency is the key event in transforming small familial H5N1 clusters into a pandemic. The Indonesian response to this large cluster has been to stage a massive simulation involving local police and military, with additional education programs planned fro the region.

Mild H5N1 would allow H5N1 to develop more efficient spread in humans and acquire Tamiflu resistance which is widespread in clade 2B H1N1 seasonal flu and may be increasing in clade 2C, which are the major forms of H1N1 currently in circulation worldwide.

The WHO has been silent on recent events. When Indonesia announced the news blackout on confirmed human cases, WHO noted that withholding of information from citizens in Indonesia did not preclude notification of WHO. However, since the news blackout was announced, the cases announce in situation updates have been case confirmed weeks or months prior to the update. Moreover, WHO has been silent on the misdiagnosed cases in the earlier clusters, as well as the large cluster in Makassar.

The efficient spread of mild H5N1 and lack of WHO comments remain causes of concern.