# 4065
The ECDC (European Centre for Disease Prevention and Control) releases a daily (5 times a week) update on the influenza pandemic, with the latest numbers along with update on recent news and their analysis or comments.
On Friday of last week 3 big stories carried the day; the announcement by the Norwegian Health Officials that they’d discovered a mutation in the H1N1 virus and two separate reports (North Carolina & Wales) of multiple cases of Tamiflu resistance.
Not surprisingly, wild Internet rumors, rampant speculation, and conspiracy theories have already begun to appear regarding these events. What most of these stories lack in logic and evidence they make up for with imagination and chutzpah.
Before I get letters, I will gladly stipulate that `official statements’ from many government agencies (and NGOs) from around the world are often carefully crafted to impart a reassuring tone, sometimes gloss over important information, and must be read with a certain amount of skepticism as well.
Some official sources are more reliable than others, but Caveat Lector is a good policy, regardless of the source.
Today the ECDC releases their Monday morning update with some analysis of the events of late last week. This is a far more detailed release of information than we saw from the WHO on Friday.
Mutation in the Haemagglutinin gene of pandemic Influenza A(H1N1)v reported from Norway
The Norwegian Institute of Public Health reported on 20 November 2009 the detection of a mutation in the viruses affecting three cases of severe pandemic Influenza A(H1N1)v infection.
Overall approximately 70 influenza viruses from ill patients have been sequenced in Norway, including six from patients who died. The three viruses with this mutation were isolated from the first two fatal cases of pandemic influenza in Norway and one patient with severe respiratory disease.
The two fatal cases , who were not epidemiologically linked, died in July and August, 2009. Based on the currently available information it appears that the mutated virus is not circulating in the Norwegian population, but may the result of a spontaneous change occurring in severely ill patients [1].
In a note responding to the report from Norway WHO reported that worldwide, a similar mutation has been was detected in viruses from several other countries, with the earliest detection reported in April. In addition to Norway, the mutation has been observed in Brazil, China, Japan, Mexico, Ukraine and the USA.[2]
ECDC comment:
The amino acid change in the haemagglutinin HA1 gene at position 222 (225 in influenza H3 numbering) from aspartic acid (D) to glycine (G) observed, may influence receptor binding specificity and therefore has the potential to affect the pathogenicity of the virus.
This might allow the mutated virus to infect tissues deeper in the respiratory tract, although the receptor binding preferences have not been determined yet. Currently, there is no evidence about the consequences of this mutation on the biological properties of the virus.
In addition, if the receptor preference of the mutated virus corresponds to the deeper airways, this most likely will tend to reduce the likelihood for easy human-to-human spread. A likely explanation of this finding is that it is an adaptive mutation of the virus.
At this moment there is no indication of change in the virulence of the circulating pandemic Influenza A(H1N1)v virus. The virus with this mutation remains sensitive to oseltamivir and zanamivir. Studies show that the currently available vaccines confer protection.
Continued close virological monitoring in particular of severe cases, is needed to elucidate any potential relationship between the mutation and the clinical outcome of infection.
Two clusters of possible transmission of oseltamivir resistant Pandemic Influenza A(H1N1)v among hospitalized patients, United Kingdom and United States
UK: Nine Pandemic Influenza A(H1N1)v confirmed cases have been reported amongst patients on a hospital ward in Wales.[3] Five of these cases are determined to be resistant to oseltamivir, one is sensitive and for three resistance status is currently unknown. The cluster is in a group of patients with haematological problems which result in immuno-suppression either because of the disorder or the chemotherapy given to treat the disorder.
Although further epidemiological investigation is underway, it would seem likely that transmission of oseltamivir-resistant H1N1 virus has taken place. Further follow-up of cases and their close contacts both on the ward and in the community is underway to ascertain if there is evidence of transmission. The virus remains sensitive to the other licensed neuraminidase inhibitor zanamivir which is being used as an alternative antiviral and to which patients are responding.[3]
USA: Four patients at a hospital in North Carolina who developed influenza in October were found to have oseltamivir resistant pandemic influenza A(H1N1) [4]. The cluster was detected when the patients did not respond to oseltamivir treatment. Three of the four patients have died. All of the patients were located in a ward for people with cancer or severe blood disorders. All were severely ill and were highly susceptible to infections.
Preliminary genetic evidence suggests that the virus spread among patients at the hospital. The U.S. Centers for Disease Control and Prevention (CDC) is testing virus samples from the patients at Duke to see whether they're indistinguishable from one another. In addition to investigating the hospital cluster, state and federal epidemiologists are trying to determine whether oseltamivir resistant influenza is circulating elsewhere in North Carolina.
ECDC comment:
Oseltamivir resistance to influenza viruses is well documented in immunosuppressed individuals and can develop quickly if oseltamivir is being given. It is likely to be associated with the high viral load which may occur during infection in these patients. In addition, immunosuppressed people may be more susceptible to infection (i.e., a smaller exposure may result in infection in these patients). It is thus not surprising that spread of resistant virus may occur from patients in whom resistance is more likely to develop during treatment to patients who are very susceptible, especially in a confined setting such as a hospital ward.
The range of manifestations (e.g., asymptomatic, mild, severe) of influenza infection, such as observed with the 2009 A(H1N1) pandemic, makes it difficult, if not impossible, to determine if any given patient or healthcare worker is carrying virus. Thus, people in contact with an index patient can innocently spread influenza to other patients.
Unvaccinated healthcare workers and visitors in contact with these patients may be at risk for being infected with this resistant strain. At this time it is difficult to predict the likelihood of spread of this resistant strain into the community through these people or another means.
The conditions under which these clusters occurred are likely to be present at other medical centres throughout the EU. That is, transmission of influenza in the community with immunocompromised patients in healthcare settings receiving either prophylactic or therapeutic oseltamivir. Thus, member states should remain vigilant for similar clusters now and in the future.
Unless oseltamivir resistance becomes more common, it remains appropriate to use oseltamivir for the treatment and prophylaxis of influenza in the UK, the US and elsewhere. Treatment failure is a reason to consider alternative treatment and to test a viral isolate for resistance. The continuous surveillance for resistance from a sample of isolates taken from community infections should be maintained in countries where resources for testing are available.
Countries without resistance testing capacity should send samples elsewhere for testing on a periodic basis. The best ways to prevent the spread of antiviral susceptible and antiviral resistant influenza in the healthcare setting and between healthcare settings and the community is to ensure healthcare workers are immunized and that there is strict adherence to infection control procedures.
