In order to help Indonesia improve its high human mortality due to bird flu (H5N1 influenza), more effective diagnostic methods must be used and improved case management must be implemented to achieve faster treatment with antivirals, according to the authors of an article released on August 14, 2008 in The Lancet.
Most of us are familiar with the flu, which seasonally affects many populations. Because it is an RNA virus, it will undergo genetic shifts relatively rapidly, providing challenges for scientists in creating vaccines. Avian influenza, also known as bird flu or H5N1 has achieved notoriety recently as it has transmitted from birds to humans with often fatal outcomes.
Internationally, the most human cases of bird flu have been found in Indonesia, which also has one of the highest case-fatality rates. While surveillance systems have been implemented to increase awareness to potential outbreaks, there are still significant risk factors that exist in this country.
To investigate the factors that contribute to the fatality of bird flu in Indonesia, Dr Toni Wandra, Directorate General of Disease Control and Environmental Health, Ministry of Health, Jakarta, and colleagues analyzed all 127 bird flu cases manifesting between June 2005 and February 2008. Each case was investigated by teams for epidemiological and clinical data from both case investigation reports and interviews with patients, family members and other individuals associated with the case.
In the first two days after onset, most patients had non-specific symptoms. That is, of the 122 patients with complete data, 25% had both fever and cough, and 7% had fever with breathing problems. The symptoms upon reaching the hospital were as follows: 99% had fever (121 cases), 88% had cough (107 cases), and 84% (103 cases) had breathing problems.
The median time from onset to treatment with oseltamivir was seven days. Survival frequency when compared to treatment time, the following was found, indicating a significant difference in treatment outcome between treatment in two days or less and five days or more:
- The one patient who received treatment within 2 days survived.
- Of patients receiving treatment within 2-4 days, 36% (4 of 11) survived.
- Of patients receiving treatment within 5-6 days, 38% (6 of 16) survived.
- Of patients receiving treatment in 7 or more days, 19% (10 of 44) survived.
Examining mortality in total, 81% of all infected patients (103 cases) died. The median hospitalization time for these patients was six days. Mortality was lower in cases that were clustered together rather than primary, stand-alone cases. For secondary cases, due to clusters, the median treatment time was five days instead of seven. Mortality was higher in cases that resided in urban areas or from indirect exposure to infected poultry through an intermediate.
The authors conclude that improving treatment times can help improve outcomes for bird flu cases. “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.” Additionally, they point out, investigations in the surveillance system should include any history of contact with poultry, especially dead and sick poultry, for all illness similar to influenza. They add: “”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.”
Prof. Sheila Bird, Medical Research Council (MRC) Biostatistics Unit, Cambridge, UK, and Jeremy Farrar, Professor of Tropical Medicine, Oxford University, contributed an accompanying comment in which they emphasize the importance of early preventative action. “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.”
Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series
I Nyoman Kandun, Erna Tresnaningsih, Wilfried H Purba, Vernon Lee, Gina Samaan, Syahrial Harun, Eka Soni, Chita Septiawati, Tetty Setiawati, Elvieda Sariwati, Toni Wandra
highest case-fatality rates worldwide. We described the factors associated with H5N1 case-fatality in Indonesia.
Lancet Online August 14, 2008
DOI:10.1016/S0140-6736(08)61125-3
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Minimum dataset needed for confirmed human H5N1 cases
Sheila M Bird, Jeremy Farrar
Lancet Online, August 14, 2008
DOI:10.1016/S0140-6736(08)61126-5
Written by Anna Sophia McKennety