Editorial Commentary: Host and Viral Factors in Emergent Influenza Virus Infections
David S. Hui
1
Frederick G. Hayden
0
0
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine
,
Charlottesville
1
Department of Medicine and Therapeutics, Chinese University of Hong Kong
, Shatin
-
Human cases of avian influenza A
(H5N1) virus infection were first
documented in Hong Kong in 1997 [1, 2];
the virus reemerged in 2003 to spread
intercontinentally and become entrenched
in poultry in other parts of Asia and
Egypt. Sporadic human cases with an
estimated case fatality rate close to 60%
continue to occur [3]. Influenza A(H1N1)
pdm09 virus first emerged in 2009 as a
novel swine-origin strain that rapidly led
to a pandemic [4] and remains a common
circulating strain. Human infections with
the novel avian influenza A(H7N9) virus,
first reported in China in March 2013 and
subsequently declining after closure of
live poultry markets, have reemerged
since October 2013 in mainland China
and spread to Hong Kong in December
2013 [5]. All 3 types of influenza viruses
continue to pose significant threats to
human health globally.
The retrospective cohort study
published by Wang et al in this issue of Clinical
Infectious Diseases [6] compares the
demographic features, risk factors, presenting
clinical characteristics, and outcomes
of patients hospitalized in China and
Vietnam with laboratory-confirmed avian
A(H7N9), avian A(H5N1), or A(H1N1)
pdm09 virus infection. The authors have
combined and compared data derived
from selected studies with somewhat
differing designs and time frames. For
example, data from Vietnamese patients with A
(H1N1)pdm09 or with A(H5N1)
infection from April 2009 onward are not
included [6], and population-based data
on baseline comorbidities were not
available for Vietnam. Such disparities might
have resulted in populations with
differences in variables of interest being
combined or missing for analysis. Secular
changes in case management are also
potential confounders with regard to
outcomes such as intensive care unit
admission and mortality. In the current report,
the frequency of mechanical ventilation
was slightly higher in patients with A
(H7N9), all of whom were admitted
within the past year, than in A(H5N1)
patients, whereas the case fatality rate was
substantially higher for A(H5N1).
The analysis of risk factors compares
their proportions in the general Chinese
population to those in the hospitalized
influenza patients. The findings confirm
prior studies highlighting the older age
and male predominance of A(H7N9)
patients [7], the broad similarities in clinical
and laboratory features of severely ill A
(H7N9) and A(H5N1) patients [8, 9],
and the findings that obesity, asthma, and
chronic obstructive pulmonary disease
are significant risk factors in
hospitalization for A(H1N1)pdm09 virus infections
[4]. The finding that chronic heart disease
was associated with an increased risk of A
(H7N9) hospitalization is unsurprising,
given the older age of these patients and
chronic heart diseases strong association
with seasonal influenza complications,
although only 11% of patients with A
(H7N9) reportedly had chronic heart
disease [6]. Recent retrospective analyses
examining the effects of influenza-specific
interventions have highlighted the
importance of influenza infections as
predisposing to serious cardiovascular events. Both
seasonal influenza vaccine receipt [10] and
neuraminidase inhibitor treatment for
clinically diagnosed influenza [11, 12]
have been associated with significant
reductions in subsequent acute cardiac
and stroke diagnoses.
Both viral and host factors contribute
to disease severity and outcomes across
influenza subtypes. The younger age,
infrequent presence of comorbidities (11% of
cases), and higher mortality of A(H5N1)
patients (55%) presumably reflects the
greater intrinsic virulence of A(H5N1)
viruses, although these viruses also show
substantial genetic diversity and
differences in virulence and treatment response in
ferrets [13] and perhaps in patients [14].
Although the absolute risk of severe
disease is thankfully much lower for A
(H1N1)pdm09 infection compared with
A(H5N1) and A(H7N9), younger age
was also a risk factor for increased
likelihood of hospitalization and mortality,
relative to seasonal influenza, during the first
year of the pandemic [15]. Of note, the
pattern of excess deaths in those aged <65
years may continue up to a decade after
introduction of a pandemic strain [16],
consistent with recent reports of severe A
(H1N1)pdm09 virus infections in the
United States (http://emergency.cdc.gov/
HAN/han00359.asp) and elsewhere.
One counterintuitive observation in
the current report was an apparent
protective effect of smoking on
hospitalization across all 3 virus subtype cohorts.
One possible hypothesis is that
nicotinerelated anti-inflammatory effects might
alter influenza severity in humans.
Chronic infusion of nicotine at doses chosen to
model plasma levels of those fou (...truncated)