# 684
The WHO (World Health Organization) yesterday released their latest treatment recommendations for avian influenza. First their protocol, then a brief discussion.
Since the last meeting in Hanoi, May 2005, eight new countries have reported human infections with avian influenza A(H5N1) viruses. Clinicians, epidemiologists, virologists and public health specialists from the countries with human cases, and experts in pulmonary medicine, critical care, and influenza attended the meeting to share their experiences.Participants agreed that standardizing care and promptly sharing clinical and treatment information are critically important to understanding the disease in humans and to improving clinical management.
Observations and experiences, including unpublished data, were shared by participants during the consultation. Several conclusions regarding management of patients with H5N1 illness support and expand current WHO guidance
• Experiences with early oseltamivir treatment suggest its usefulness in reducing H5N1-associated mortality. In addition, evidence of prolonged H5N1 virus replication indicates that treatment is warranted even with late presentation.
• As previously discussed, modified regimens of oseltamivir treatment, including two-fold higher dosage, longer duration and possibly combination therapy with amantadine (in countries where the H5N1 virus is susceptible to amantadine) may be considered on a case by case basis, especially in patients with pneumonia or progressive disease. Ideally this should be done in the context of prospective data collection.
• Corticosteroid therapy has failed so far to show effectiveness, and prolonged or high dose corticosteroids can result in serious adverse events in H5N1 patients, including opportunistic infection. Corticosteroids should not be used routinely, except for persistent septic shock with suspected adrenal insufficiency.
• Antibiotic prophylaxis should not be used. When pneumonia is present, antibiotic treatment is appropriate initially for community-acquired pneumonia according to published evidence-based guidelines. When available, the results of microbiologic studies should be used to guide antibiotic usage in patients with A(H5N1) infection.
• Therapy for H5N1-associated ARDS should be based upon published evidence-based guidelines for sepsis-associated ARDS, specifically including lung protective mechanical ventilation with low tidal volume.
The observations from the meeting will be published in greater detail, as an updated WHO guidance on H5N1 clinical management followed by a meeting summary in the form of peer-reviewed article in the scientific literature.
There is not a lot here we didn't already know, or at least strongly suspect. What they do is confirm current wisdom. And it should be noted that these recommendations are for a period of time where we only see sporadic cases.
Things may well change in a pandemic.
That oseltamivir (Tamiflu) is useful in the treatment of H5N1 is hardly earth shattering, and that it should be started early for the best results, has been long known.
There has been talk in some circles about denying Tamiflu to those who presented after being sick more than 48 hours, as it was felt that it was too late to do much good, but these recommendations say late treatment is warranted.
Once again, we get a clear indication that the standard course, 10-pills over 5 days, may be inadequate for severely affected patients. Double the dose, for a longer duration, may be required.
The recommendation not to use corticosteroids in high doses, except for persistent septic shock with suspected adrenal insufficiency, follows closely the experiences doctors had with SARS patients. High dose steroids were used to combat ARDS (Acute Respiratory Distress Syndrome), and they did often see early improvements in patients, but the long term survival rate was as bad, or worse, than those that did not receive that treatment.
The antibiotic advice is pretty standard, as we fear creating resistant bacteria strains, but won't be of much use later, in a pandemic. Niceties, like lab cultures, are unlikely to be available for the vast majority of flu victims in a crisis. Doctors will be forced to guess on what antibiotics to prescribe, and hope they work.
The impact of these recommendations, however, could be significant.
The United States, along with nearly every nation stockpiling Tamiflu, has less than they need for a pandemic. Increasing that course of treatment to double or quadruple (twice the dose for twice the duration) that dose would significantly reduce the number of people who could receive treatment.
What we don't know is what percentage of patients would need the higher dose. If it is only a small number, then it won't severely impact the number of treatment courses. If it turns out that most patients require this higher dose, then the number of treatment courses could be cut by half, or more.
Evidence, once again, that we can't view Tamiflu as a magic bullet for a pandemic. There simply won't be enough to go around.
NPI's (Non-Pharmaceutical Interventions) like school closings, social distancing, and handwashing are going to be our primary defenses if a pandemic erupts.
