Tuesday, May 23, 2006

WHO update on Indonesia cluster: not comforting

WHO has issued a new update on the Indonesian cluster and it wasn't very comforting. The 32 year old man who died yesterday was the father of a youngster (10 years old) who took ill on 5/3 and died on 5/13. The father took ill on 5/17. He had spent a great deal of time with his sick son and WHO suggests this was the source of his infection:
The case is part of a family cluster in the Kubu Sembelang village, Karo District, of North Sumatra. The man is the seventh member of an extended family to become infected with the H5N1 virus and the sixth to die. An additional person, who was the first member of the family to fall ill, died of respiratory disease on 4 May. No specimens were taken prior to her burial and the cause of her death cannot be determined. However, as her clinical course was compatible with H5N1 infection, epidemiologists at the outbreak site include this woman as the initial case in the cluster.

The newly confirmed case is a brother of the initial case. Specimens were taken on 21 May and flown the same day to Jakarta. Tests run overnight confirmed his infection. His 10-year-old son died of H5N1 infection on 13 May. The father was closely involved in caring for his son, and this contact is considered a possible source of infection.

Although the investigation is continuing, preliminary findings indicate that three of the confirmed cases spent the night of 29 April in a small room together with the initial case at a time when she was symptomatic and coughing frequently. These cases include the woman’s two sons and a second brother, aged 25 years, who is the sole surviving case among infected members of this family. Other infected family members lived in adjacent homes.

All confirmed cases in the cluster can be directly linked to close and prolonged exposure to a patient during a phase of severe illness. Although human-to-human transmission cannot be ruled out, the search for a possible alternative source of exposure is continuing. (WHO)
This last sentence is of some significance. If the 10 year old contracted it from one of the two sons or uncle who were infected by the index case (the mother who took ill on 4/27), then the father is either a tertiary or fourth generation case. This would be the first known case that has gone beyond one generation of infected human to human cases. The statement, "Although human-to-human transmission cannot be ruled out, the search for a possible alternative source of exposure is continuing" seems bizarre in this context. One would think it is the other way around: "Although human-to-human transmission seems the best current explanation, other sources of exposure cannot be ruled out."

An additional note gives some scanty information on sequencing of two viruses isolated from this cluster (presumably isolated and confirmed by NAMRU2 in Jakarta):
Full genetic sequencing of two viruses isolated from cases in this cluster has been completed by WHO H5 reference laboratories in Hong Kong and the USA. Sequencing of all eight gene segments found no evidence of genetic reassortment with human or pig influenza viruses and no evidence of significant mutations. The viruses showed no mutations associated with resistance to the neuraminidase inhibitors, including oseltamivir (Tamiflu).

The human viruses from this cluster are genetically similar to viruses isolated from poultry in North Sumatra during a previous outbreak.
If the sequencing is completed, why is it not being deposited immediately in GenBank (or is it)? It is not immediately obvious that the reassortments with pig and human viruses concern only HA and NA or also include all other segments. We are learning that there is a great deal of reassortment occurring among influenza viruses within subtypes. When the same HA and NA are present against new genetic backgrounds of internal genes, outbreaks can occur. There is some thought this is what is happening when one strain of the same subtype replaces another in seasonal influenza (e.g., replacement of A/Fujian(H3N2) with A/California(H3N2)). The statement that there are no significant mutations suggests non-significant ones have taken place. Does this mean the unique cleavage site mutation seen in the human but not avian viruses in Indonesia is not there?

Let's see the sequences. Now. With holding them from the world scientific community is unconscionable.