TrueScotsman
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Date: Thu 22 Apr 2010
Source: Eurosurveillance, Volume 15, Issue 16 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19546>
Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1)
infected patients in the west of Scotland, UK, 2009-10
-------------------------------------------
By: R S Miller, A R MacLean, R N Gunson, W F Carman. At: West of Scotland
Specialist Virology Centre, Glasgow, United Kingdom
To the Editor: Kilander, et al (2010) [1] have previously reported that in
some cases of patients with severe or fatal pandemic influenza A(H1N1), an
amino acid substitution from aspartic acid to glycine occurs at position
222 (D222G) of the HA1 subunit of the haemagglutinin (HA). In their study
11 (18 per cent) of 61 patients with severe disease had the mutation, in
contrast to 0 of 205 patients with mild disease.
Since the original report [1] several countries have detected this mutation
[2]. This data has been summarised in a recent World Health Organization
(WHO) review, which reported that the overall prevalence of D222G was less
than 1.8 per cent in contrast to a rate of 7.1 per cent in fatal cases [2].
The WHO paper also reports on the occurrence of other mutations at this
amino acid, D222E and D222N, although their significance is unclear. A
group in Hong Kong have also analysed this amino acid in severe and
non-severe cases of pandemic influenza A(H1N1) [3]. In this study, 9 (4.1
per cent) of 219 severe or fatal cases of pandemic influenza A(H1N1) had
the D222G mutation, in contrast to 0 of 239 non-severe cases.
We sequenced the HA1 subunit of the HA gene from a number of west of
Scotland cases, both community cases and severely ill. Furthermore, we
subdivided the severely ill into those who had died and those who recovered
after hospitalisation. We found an increased incidence of D222G in those
patients who died (2/23; 8.7 per cent) compared with both community and
hospitalised patients (0/35; 0 per cent). We also detected an increased
incidence (2/32; 6.2 per cent cf 0/26; 0 per cent) of D222N (aspartic acid
to asparigine) in severely ill patients and those who had died. The
significance of this mutation is unclear. There was a low level of D222E
(aspartic acid to glutamic acid) present in both severely ill and community
cases with no significant difference between the 2. These results are
tabulated below:
Cases / Number / D222G / D222N / D222E
All cases / 58 / 2 (3.4 per cent) / 2 (3.4 per cent) / 4 (6.9 per cent)
Deaths / 23 / 2 (8.7 per cent) / 0 / 1 (4.3 per cent)
Serious illness / 9 / 0 / 2 (2.2 per cent) / 1 (11 per cent)
Community patients / 26 / 0 / 0 / 3 (11 per cent)
Interestingly, in one of the patients who died and had the D222G mutation,
the original sequence had a mixed base in the D222 codon giving D222D/G. On
resequencing 2 more samples from this patient, we obtained a pure D222G on
one occasion and a pure wildtype D222 on the other, showing that this
patient had a mixed population of virus. This confirms the finding in
Kilander's paper [1] of the co-existence of mutant and wildtype virus.
Source: Eurosurveillance, Volume 15, Issue 16 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19546>
Occurrence of haemagglutinin mutation D222G in pandemic influenza A(H1N1)
infected patients in the west of Scotland, UK, 2009-10
-------------------------------------------
By: R S Miller, A R MacLean, R N Gunson, W F Carman. At: West of Scotland
Specialist Virology Centre, Glasgow, United Kingdom
To the Editor: Kilander, et al (2010) [1] have previously reported that in
some cases of patients with severe or fatal pandemic influenza A(H1N1), an
amino acid substitution from aspartic acid to glycine occurs at position
222 (D222G) of the HA1 subunit of the haemagglutinin (HA). In their study
11 (18 per cent) of 61 patients with severe disease had the mutation, in
contrast to 0 of 205 patients with mild disease.
Since the original report [1] several countries have detected this mutation
[2]. This data has been summarised in a recent World Health Organization
(WHO) review, which reported that the overall prevalence of D222G was less
than 1.8 per cent in contrast to a rate of 7.1 per cent in fatal cases [2].
The WHO paper also reports on the occurrence of other mutations at this
amino acid, D222E and D222N, although their significance is unclear. A
group in Hong Kong have also analysed this amino acid in severe and
non-severe cases of pandemic influenza A(H1N1) [3]. In this study, 9 (4.1
per cent) of 219 severe or fatal cases of pandemic influenza A(H1N1) had
the D222G mutation, in contrast to 0 of 239 non-severe cases.
We sequenced the HA1 subunit of the HA gene from a number of west of
Scotland cases, both community cases and severely ill. Furthermore, we
subdivided the severely ill into those who had died and those who recovered
after hospitalisation. We found an increased incidence of D222G in those
patients who died (2/23; 8.7 per cent) compared with both community and
hospitalised patients (0/35; 0 per cent). We also detected an increased
incidence (2/32; 6.2 per cent cf 0/26; 0 per cent) of D222N (aspartic acid
to asparigine) in severely ill patients and those who had died. The
significance of this mutation is unclear. There was a low level of D222E
(aspartic acid to glutamic acid) present in both severely ill and community
cases with no significant difference between the 2. These results are
tabulated below:
Cases / Number / D222G / D222N / D222E
All cases / 58 / 2 (3.4 per cent) / 2 (3.4 per cent) / 4 (6.9 per cent)
Deaths / 23 / 2 (8.7 per cent) / 0 / 1 (4.3 per cent)
Serious illness / 9 / 0 / 2 (2.2 per cent) / 1 (11 per cent)
Community patients / 26 / 0 / 0 / 3 (11 per cent)
Interestingly, in one of the patients who died and had the D222G mutation,
the original sequence had a mixed base in the D222 codon giving D222D/G. On
resequencing 2 more samples from this patient, we obtained a pure D222G on
one occasion and a pure wildtype D222 on the other, showing that this
patient had a mixed population of virus. This confirms the finding in
Kilander's paper [1] of the co-existence of mutant and wildtype virus.