# 7422
One of the enigmas surrounding the H5N1 virus is the wide disparity in fatality rates between countries. As you can see from the chart above, Indonesia’s CFR (Case Fatality Ratio) is more than twice that of Egypt.
Of the nations that have reported cases, Bangladesh has the best record, with only a 14% fatality rate.
Granted, these numbers are likely skewed by differences in surveillance, testing, and reporting around the world, but they are what we have to work with.
One of the unknowns is the relative health impact of different clades of the H5N1 virus (until recently, Indonesia had only dealt with clades 2.1.1, 2.1.2. and 2.1.3, but now adds 2.3.2. – while clades 2.2.1 and 2.2 are endemic in Egypt).
But other factors have been posited, including delays in seeking healthcare and, once sought, the speed and quality of diagnosis and treatment.
A study, recently published in BMC Public Health, looks at the treatment and outcome of 124 cases of H5N1 infection reported in Indonesia between 2005 and 2010, and finds serious delays in the time between seeking medical treatment and an accurate diagnosis and antiviral treatment for the virus.
Human influenza A H5N1 in Indonesia: health care service-associated delays in treatment initiation
Wiku Adisasmito, Dewi Nur Aisyah, Tjandra Yoga Aditama, Rita Kusriastuti, ¿ Trihono, Agus Suwandono, Ondri Dwi Sampurno, ¿ Prasenohadi, Nurshanty A Sapada, MJN Mamahit, Anna Swenson, Nancy A Dreyer and Richard Coker
BMC Public Health 2013, 13:571 doi:10.1186/1471-2458-13-571
Published: 11 June 2013
Abstract (provisional)
Background
Indonesia has had more recorded human cases of influenza A H5N1 than any other country, with one of the world's highest case fatality rates. Understanding barriers to treatment may help ensure life-saving influenza-specific treatment is provided early enough to meaningfully improve clinical outcomes.
Methods
Data for this observational study of humans infected with influenza A H5N1 were obtained primarily from Ministry of Health, Provincial and District Health Office clinical records. Data included time from symptom onset to presentation for medical care, source of medical care provided, influenza virology, time to initiation of influenza-specific treatment with antiviral drugs, and survival.
Results
Data on 124 human cases of virologically confirmed avian influenza were collected between September 2005 and December 2010, representing 73% of all reported Indonesia cases. The median time from health service presentation to antiviral drug initiation was 7.0 days. Time to viral testing was highly correlated with starting antiviral treatment (p < 0.0001). We found substantial variability in the time to viral testing (p = 0.04) by type of medical care provider. Antivirals were started promptly after diagnosis (median 0 days).
Conclusions
Delays in the delivery of appropriate care to human cases of avian influenza H5N1 in Indonesia appear related to delays in diagnosis rather than presentation to health care settings. Either cases are not suspected of being H5N1 cases until nearly one week after presenting for medical care, or viral testing and/or antiviral treatment is not available where patients are presenting for care. Health system delays have increased since 2007.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
The therapeutic effects of antivirals, like oseltamivir, are the most pronounced in the first 48 hours of infection. After that, some benefit may be derived, but its effects are greatly diminished.
In Indonesia, this study found the average time between seeking medical treatment, and receipt of antivirals, was 7 days. Too late to have much effect.
The authors write in the discussion section:
A low clinical suspicion of disease by health care workers likely remains an important impediment to early diagnosis, virological confirmation, and appropriate treatment initiation [13].
The signs and symptoms during the first two days of disease in cases reported here were mostly non-specific. This nonspecific clinical presentation of influenza A (H5N1) disease raises challenges.
The differential diagnosis of cases may include other influenza-like illnesses, dengue, or typhoid [14], to the exclusion of influenza A (H5N1). In an earlier report, only 12% of influenza H5N1 cases were initially diagnosed as having influenza H5N1
[13].
There’s a good deal of data included in this report, including demographic information on cases, CFRs based on the type of medical facility where patients were first seen, and a detailed list - by patient symptoms – of the time to seeking medical care, time to testing, and time to antiviral treatment.
The authors conclude by writing:
Conclusions
Reducing health care system delays in the initiation of specific treatment for patients infected with influenza H5N1 is no easy matter. The non-specific nature of the disease, especially in the early days, suggests a number of options that might be considered.
The application of rapid diagnostic tests on presentation to confirm or refute the diagnosis might enable clinicians to tailor their treatment better. Alternatively, the initiation of treatment when clinical suspicion is raised might offer benefits to the minority who actually have influenza H5N1.
Both of these approaches have cost implications that need to be determined. Prospective clinical studies too may offer more robust data on clinical symptoms and signs associated with differentiating H5N1 from other diseases as well as determining those likely to fare least well clinically and thus benefit most from influenza specific clinical interventions.
