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Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series

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Development of better diagnostic methods and improved case management could speed-up identification of bird flu cases in humans (H5N1 influenza), and in turn lead to faster treatment with antiviral drugs to decrease Indonesia’s extremely high mortality due to the disease.


These are the conclusions of authors of an Article published early Online and in an upcoming edition of The Lancet.Indonesia has had the most human cases of bird flu, and one the highest-case-fatality rates worldwide. Dr Toni Wandra, Directorate General of Disease Control and Environmental Health, Ministry of Health, Jakarta, Indonesia, and colleagues analysed the factors associated with bird flu fatality in Indonesia. Between June 2005 and February 2008 there were 127 confirmed bird flu infections. Investigation teams were deployed to investigate and manage each confirmed case; they obtained epidemiological and clinical data from case-investigation reports when possible and through interviews with patients, family members, and key individuals.

The researchers found that 103 (81%) of infected patients died, with a median time to hospitalisation of six days. On reaching hospital, of 122 patients with complete data, 121 (99%) had fever, 107 (88%) had cough, and 103 (84%) had breathing problems. However, for the first two days after onset, most patients had non-specific symptoms; only 31 had both fever and cough, and nine had fever and breathing problems. Median time from onset to treatment with the antiviral drug oseltamivir was seven days. Treatment started within two days for one patient, who survived. Four of 11 (36%) of patients receiving treatment within 2–4 days survived, six of 16 (38%) of patients receiving treatment within 5–6 days survived, and 10 of 44 (19%) receiving treatment at seven days or later survived. Starting treatment within two days was associated with significantly lower mortality than was starting treatment at days 5–6 or later. Mortality was lower in clustered cases (ie, those that were part of one collective outbreak) than primary, stand-alone cases; and treatment started at a median of five days from onset in secondary cases in clusters compared witheight days for primary cases. Residence in an urban area and indirect exposure* were also positively associated with mortality.

The authors conclude: “Early case identification and treatment with oseltamivir is key to addressing the high case-fatality rate in Indonesian cases. There is a clear need to identify definite causes for high-case fatality...While additional research is done we propose the following strategies to provide early diagnosis and prompt treatment to improve quality of case management. Poultry surveillance is being stepped up, and active human case finding by local health centres and village officials is being instituted in areas of poultry deaths.” They add that investigations should include thorough history of contact with poultry, especially dead and sick poultry, for all patients with influenza like illness. They conclude: “This strategy will promote earlier and targeted detection of patients that have clear exposure to diseased birds, which should then prompt earlier treatment and reduced case fatality. Finally, all health-care workers should be trained in case management of early H5N1 influenza, and should be equipped with oseltamivir to enable timely administration.”

In an accompanying Comment, Prof Sheila Bird,Medical Research Council (MRC) Biostatistics Unit, Cambridge, UK, and Jeremy Farrar, Professor of Tropical Medicine, Oxford University say: “Consideration needs to be given now—not in the teeth of a pandemic, and not deflected by either proprietary defensiveness or opportunistic profiteering—to gauging the comprehensiveness of national surveillance for human H5N1 cases. And to ensuring the analysability of a minimum dataset on the exposures and clinical course of every confirmed case of human H5N1. The world also needs to find a more equitable way to ensure that all share in the benefits of such important research. Indonesia could give the lead here.”

Source institution:

United Nation System Influenza Coordination (UNSIC)

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