Prominent among this publication’s recent listing of
the
"
red-hot research papers" of 2009 are reports, in the
astrophysics literature, from something called the Wilkinson
Microwave Anisotropy Probe (Science Watch, March/April
2010). However, not far behind lie three publications that might be
considered of rather more immediate earthly interest. They are on
"swine flu, not perhaps the best term for the disease that has
swept the world since pandemic H1N1/09 influenza virus first
attracted attention just over a year ago.
For one thing, influenza in pigs has long been a worry for animal
husbandry without (usually) transmission to humans. For another,
H1N1/09 has not (yet) caused outbreaks in swine—but if it did
an alarming "Pandora’s box" might be opened (J. Cohen,
Science, 325[5937]: 140-1, 2009).
Colorized negative stained transmission
electron micrograph (TEM) depicted some of the
ultrastructural morphology of the A/CA/4/09
swine flu virus.
Paper #2 in the current Medicine Top Ten, from the Novel
Swine-Origin Influenza A
(H1N1)
Investigation Team, wound up 7th among 2009’s most-cited
publications. At #14 (having finished 18th in the 2009 tally) is a
study from the WHO Rapid Pandemic Assessment Collaboration
(C. Fraser, et al.,
Science, 324[5934]:1557-61, 2009; total cites 81,
latest count 40). Another large collaboration is currently at
#15 among medicine’s hottest (#39 on the other list): R.J.
Garten, et al., Science, 325[5937]: 197-201,
2009; total cites 60, latest count 40.
Those three reports are the early fruits of an international
cooperative effort triggered by the identification, in mid-April
2009, of two patients in California infected with a novel influenza
A virus. Within two weeks of the identification of this virus both
the World Health Organization (WHO) and the U.S. authorities had
declared a public-health emergency. By the end of that April WHO
had already raised the global pandemic alert to phase 5 (out of
six). The genomic make-up of the virus meant that the then current
vaccine was unlikely to offer protection.
Dr. Fatimah S. Dawood and colleagues (paper #2) record details of
the first 642 U.S. cases. The dominant symptoms were fever, cough,
and sore throat but a quarter of patients had diarrhea and
vomiting. Three-fifths of patients were under 19 years of age. The
paper notes that numbers of laboratory-confirmed cases probably
underestimate total infections. Although 22 patients in this series
required hospital care (and two of them died), influenza is usually
self-limited and self-treated and medical help is not sought.
This point is confirmed in a large seroepidemiological study from
England (E. Miller, et al., Lancet, 375[9720]:
1100-8, 2010), suggesting that infections outnumber estimates from
clinical surveillance by a factor as high as 10. The English
experience also confirms the vulnerability of children.
Interestingly, serum samples from before April 2009 showed that 23%
of adults over 65 had protection against the new virus.
Of the other two papers, in Science, the one by Prof.
Christophe Fraser and colleagues (#14) focuses on the virus’s
pandemic potential (see also PLoS Curr Influenza RRN 1135,
2009[Dec 16]). A key figure is the number of cases one case
generates (here 1.2 to 1.6, depending on the method used). The data
come from Mexico, where the disease seems to have started, and
indicate that between 14 and 73 generations of human-to-human
transmission had occurred in that country by late April 2009.
Transmissibility for this infection is much higher than that for
seasonal influenza, a fact that contributed to WHO’s
upgrading of the pandemic status. It is more the antigenic and
genetic features of swine-origin 2009 A (H1N1) that are the focus
in #15. Again, the findings fuel anxiety for the future.
Circulation in humans of an influenza virus with an "antigenically
and genetically divergent HA [hemagglutinin] and a
previously unrecognized genetic composition is of concern to public
health officials around the world."
In the U.K. pandemic influenza A (H1N1) has dropped right out of
the news, despite a predictable second peak last October. The
National Pandemic Flu Service closed in February 2010, and both
here and in the U.S. the most recent official figures show small
infection numbers. The epidemiological and virological data in #2,
#14, and #15, however, argue against any
complacency.
A former deputy editor of The Lancet, David.
W. Sharp, M.A. (Cambridge) is a freelance writer living in
Minchinhampton, U.K.
Medicine
Top 10 Papers
Rank
Paper
Citations
This Period
(Nov-Dec 09)
Rank
Last Period
(Sep-Oct 09)
1
J. Yu, et al.,
"Induced pluripotent
stem cell
lines derived from human somatic
cells,"Science, 318(5858):
1917-20, 21 December 2007.
[Genome Ctr. Wisconsin, Madison;
U. Wisconsin, Madison] *243HE
93
1
2
Novel Swine-Origin Influenza A
(H1N1) Virus Investigation Team
(F.S. Dawood, et al.),
"Emergence of a novel
swine-origin influenza A (H1N1)
virus in humans,"New
Engl. J. Med., 360(25):
2605-15, 18 June 2009. [Writing
group: Ctrs. for Disease Control
& Prevent., Atlanta, GA] *458WR
81
†
3
The ADVANCE Collaborative Group (A.
Patel, et al.),
"Intensive blood glucose
control and vascular outcomes in
patients with type 2
diabetes,"New Engl.
J. Med., 358(24): 2560-72, 12
June 2008. [Writing Group: 18
institutions worldwide] *311IJ
76
3
4
The ACCORD Study Group (H.C.
Gerstein, et al.),
"Effects of intensive
glucose lowering in type 2
diabetes,"New Engl.
J. Med., 358(24): 2545-59, 12
June 2008. [Writing Group: 10 U.S.
and Canadian institutions] *311IJ
73
2
5
R.R. Holman, et al.,
"10-year follow-up of
intensive glucose control in type 2
diabetes,"New Engl.
J. Med., 359(15): 1577-89, 9
October 2008. [6 U.K. institutions]
*358FS
52
5
6
I.H. Park, et al.,
"Reprogramming of human
somatic cells to pluripotency with
defined factors,"Nature, 451(7175): 141-6,
10 January 2008. [Harvard Med.
Sch., Boston, MA; Harvard Stem Cell
Inst., Boston, MA] *249GA
50
10
7
J.M. Llovet, et al.,
"Sorafenib in advanced
hepatocellular carcinoma,"New Engl. J. Med., 359(4):
378-90, 24 July 2008. [22
institutions worldwide] *329FK
48
7
8
The ONTARGET Investigators (S.
Yusuf, et al.),
"Telmisartan, ramipril, or
both in patients at high risk for
vascular events,"New
Engl. J. Med., 358(15):
1547-59, 10 April 2008. [Writing
committee: 5 institutions
worldwide] *285NK
47
†
9
W. Duckworth, et al.,
"Glucose control and
vascular complications in veterans
with type 2 diabetes,"New Engl. J. Med., 360(2):
129-39, 8 January 2009. [11 U.S.
institutions] *391UG
47
†
10
K. Miller, et al.,
"Paclitaxel plus
bevacizumab versus paclitaxel alone
for metastatic breast
cancer,"New Engl. J.
Med., 357(26): 2666-76, 27
December 2007. [9 U.S. and Canadian
institutions] *245UO