KY Yuen

Within a period of nine months from May 1997 to January 1998, eighteen patients which included 11 children came down with this 'avian flu' with an overall mortality of 33%. This astonishingly high mortality rate of Influenza A H5N1 compared with the rate of 0.01% of the usual subtype H3N2 could be partly explained by the very low prevalence of neutralising antibody against H5 in our general population. Another important explanation came from the local and overseas molecular studies which suggested that the characteristic cleavage-site sequence in H5 is susceptible to effect of a wide spectrum of cellular proteases present in various tissues. Therefore this virus may have unusual tissue tropism beyond the respiratory tract. Besides the upper (67%) and lower respiratory tract involvement (61%), a high proportion of these patients had gastrointestinal syndrome (50%), liver dysfunction (44%), renal dysfunction (22%), leucopenia and lymphopenia (61%), and hemophagocytosis (11%), which may explain the unusual severity of disease in human beings.

Another important observation is the age-related dichotomy in clinical presentation and final outcome. Except for the 3 year old boy who succumbed to Reye's syndrome associated with the intake of aspirin, young children less than the age of 5 uniformly recovered from the mild upper respiratory infection and fever. On the contrary all the older children and adult suffered from severe disease which required respiratory support. Postulations to account for such dichotomy could be occupational or behavioral difference which may lead to a different dose of viral exposure. Other mechanisms that may account for a more severe disease in adults include immunopathology mediated by non-protective cross-reacting antibody or cell-mediated immune response due to past exposure to homologous viral antigens. Further immunological study on this phenomenon should be undertaken to ascertain if immunotherapeutic strategy may lessen the severity of disease in the older patients.

As in any emerging infectious disease, a rapid diagnostic method is vital for case identification, epidemiological tracing and early specific therapy. The H5-specific RTPCR assay appears to be a promising technique for the rapid direct detection of the virus from clinical specimens.¹ The direct immunofluorescent antigen test specific for H5 is also useful for exclusion of H5 in specimens positive for flu A by the ELISA test (Directigen) which is not specific for H5. This has provided reassurance to panicking patients or parents and allowed early discharge from the hospital.

Presently there is no proven anti-viral agent which is efficacious for patients suffering from severe primary influenza pneumonia. Amantadine is only proven to shorten the duration of flu syndrome by 50% if given within 48 hours of onset of symptoms. Two-third of our patients which included most of our severe cases presented later than 3 days after the onset of symptoms. The therapeutic efficacy of amantadine on influenza H5N1 could not be ascertained since only 58% of the survivors and 67% of the fatal cases were treated with this agent. Aerosolised ribavirin, the newer neuraminidase inhibitors or high titre H5 specific antisera obtained from convalescent patient or immunised volunteers should be considered if further severe cases occur.

Genetic similarity of the viral strains from patients and chickens suggest that the avian H5N1 virus had crossed the avian-human species barrier without prior adaptation in another mammalian species.² Data on the seroprevalence of the general population, poultry worker, household contact and medical staff contacts of patients suffering from this 'bird flu' also suggest that this disease is a zoonosis which is transmitted predominantly from poultry to human. The low efficiency of human-to-human transmission precluded the possibility of a major epidemic in Hong Kong evolving into a global pandemic unless subsequent mutations or genetic ressortment allow for a better adaptation of this avian virus to a human host. However, the poor adaptability of this unsuccessful virus is perhaps one of the important reason accounting for the high mortality in infected human. Complacency at all levels of the medical community should be discouraged despite the apparent success of the massive chicken slaughter exercise. Remember that the disease has been expected to die out since there is not a single case between May and November 1997. It would be a grave mistake if attention to this zoonosis is slackened at this stage. New emerging infectious diseases including zoonosis would continue to surface in Hong Kong which is being strained by her historically unprecedented overcrowding and busy international travel.

References

1. Yuen KY, Chan PKS, Peiris M, et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998;351:467-71.

2. Class EC, Osterhaus ADME, van Beck R, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998;351:472-77.