[Marxism] "Considering the potential death toll of a 1918-like influenza pandemic..."

[Andy <esquincle@xxxxxxxxxxx>]

The New England Journal of Medicine
Volume 351:2363-2365
December 2, 2004
Number 23

Avian Influenza — A Challenge to Global Health Care Structures

Tran Tinh Hien, M.D., F.R.C.P., Menno de Jong, M.D., Ph.D., and Jeremy 
Farrar, D.Phil., F.R.C.P.

The largest, most devastating outbreak of an infectious disease in 
modern history occurred in 1918, when a highly virulent influenza A 
(H1N1) virus spread throughout the world and killed between 20 million 
and 40 million people. Additional epidemics occurred in 1957 (H2N2) and 
1968 (H3N2), both originating in Asia and each killing approximately 1 
million people. These haunting memories have led to widespread concern 
about the ongoing outbreak of avian H5N1 influenza in Asia.

Certain parallels between the "Spanish flu" of 1918 and H5N1 justify 
this concern. Like the 1918 virus, H5N1 influenza has unusually high 
virulence and can capitalize on an absence of preexisting immunity in 
humans, at least in certain age groups. Although the two viruses differ 
in their transmissibility among humans, there is concern that currently 
circulating H5N1 viruses will evolve into a pandemic strain by adapting 
to humans through genetic mutation or reassortment with human influenza 
strains (see diagram). Although it seems that this has not yet 
occurred, recent studies have demonstrated continued evolution of the 
virus since the H5N1 outbreak in Hong Kong in 1997. The goose precursor 
virus of the H5N1 strains that caused that avian influenza outbreak has 
since evolved into a dominant pathogenic genotype, now endemic among 
poultry in Asia, with a host range that has expanded to include 
terrestrial poultry and wild birds.1 It is this genotype that is 
implicated in the recent human infections.
 
[illustration a cellular cartoon]
Generation of a Potentially Pandemic Strain of Influenza through 
Reassortment.

Reassortment of genes between avian and human strains of influenza, 
which is facilitated by the division of the influenza A genome into 
eight segments, can occur during coinfection with both strains. Such 
coinfection may occur in pigs, which would support the growth of both 
avian and human viruses, or it may occur in humans.
 
Other studies have shown that H5N1 viruses isolated between 1999 and 
2002 seemed to acquire the ability to replicate in mammals, possibly as 
a result of transmission between ducks and pigs.2 The possibility that 
the host range of H5N1 has broadened to include mammals is supported by 
recent reports of H5N1 infections in cats3 and news reports about 
tigers in a Thai zoo that have become ill or died after eating raw 
chicken. In comparison, studies of the 1918 strain indicate that the 
hemagglutinin protein, although avian in origin, preferentially bound 
to human receptors, suggesting that it circulated in humans or other 
species with human-like receptors (e.g., pigs) for long enough to 
develop this receptor preference.4 The broadening host range of H5N1 
viruses and the recently reported H5N1 infection of pigs,2 combined 
with endemicity of contemporary human H3N2 viruses among pigs in 
southern China1 and the continuing occurrence of sporadic human H5N1 
infections,5 are obvious concerns; it is possible that the current 
situation resembles the undocumented events that led to the 1918 
pandemic.

Today, modern laboratory techniques, clinical and epidemiologic 
knowledge, and global communication provide the opportunity to monitor 
the evolving outbreak and act on it. However, in many of the countries 
affected by the H5N1 virus, access to these tools is still very 
limited, severely hampering the ability to track the emergence of 
pathogens.

Despite the decimation of the poultry industry throughout much of Asia 
and initial optimism that the outbreak had been curbed, new cases of 
human H5N1 infection have been documented since our report of the first 
10 patients.5 At the time of this writing, there have been a total of 
43 proven human H5N1 infections, of which 31 have been fatal, and 
Cambodia, China, Indonesia, Laos, Malaysia, Thailand, and Vietnam have 
all reported H5N1 in their poultry (see map). Although human infections 
have been documented only in Thailand and Vietnam, it seems likely that 
additional cases have occurred in other countries but have remained 
unrecognized because of a lack of clinical awareness or diagnostic 
facilities.

[illustration:  map of Asia]
Countries Reporting Avian Influenza during 2004.
Information is from the World Organization of Animal Health.
 
On the basis of the current figures for the reported cases, the 
mortality associated with human H5N1 infection is remarkably high — 72 
percent, as compared with an estimated 2.5 percent for Spanish 
influenza. However, it is uncertain whether milder cases of human H5N1 
infection have occurred. If so, this would be further evidence of the 
potential for the virus to adapt to humans. Insight into the full 
clinical spectrum of the illness in humans is critical but requires 
sustained surveillance, which is not feasible in most affected 
countries, owing to technical, logistic, and financial constraints. 
Such surveillance would also yield epidemiologic and virologic data on 
circulating human influenza strains. The absence of such data in many 
of the affected countries precludes assessment of the risk of 
reassortment, as well as rational decision making concerning the 
possibility of vaccinating people against prevailing human influenza 
strains in an effort to prevent reassortment. Finally, active 
surveillance in animals and humans would permit close monitoring of the 
evolution of the current H5N1 viruses, as well as early recognition of 
other potentially threatening avian viruses.

Fortunately, there has been no direct evidence of efficient 
poultry-to-human or human-to-human transmission to date. That there 
have been relatively few cases in humans despite huge numbers of 
infected poultry seems reassuring. The only documented case of probable 
human-to-human transmission involved prolonged, unprotected, intimate 
exposure to a child who was dying of unconfirmed but highly suspected 
H5N1 infection. Such transmission underscores the importance of 
infection-control measures in cases of suspected avian influenza. The 
absence of other secondary cases and the absence of substantial genetic 
changes in the virus in this case are reassuring, as is the absence of 
reported illnesses among health care workers involved in the care of 
patients with H5N1 infection.

In 1997, the H5N1 outbreak in Hong Kong was controlled through the 
killing of all poultry, a strategy that may prove less successful in 
the current outbreak, since it is much more extensive and most of the 
countries involved are less well developed. Furthermore, the potential 
role of wild birds in maintaining and spreading the virus may be a 
complicating factor.1 H5N1 vaccination may be essential for effective 
control but would require global efforts to ensure sufficient 
production of vaccine and to address important economic issues related 
to vaccination (the cost of vaccination and the potential loss of 
export markets for poultry that tests positive for H5N1 after 
vaccination).

Long-term solutions for preventing or adequately managing future 
problems deserve urgent attention. In the era of global travel, the 
time available for instituting effective public health measures during 
an outbreak will be very limited. One of the key lessons of the current 
H5N1 outbreak is the importance of having in each country the clinical, 
scientific, and technical capacity to identify a problem and the 
knowledge necessary to respond to it. Notwithstanding the crucial role 
played by international and regional centers of excellence in 
coordinating surveillance and defending against global pandemics, it is 
people on the ground in affected countries who need to have the 
necessary infrastructure at their immediate disposal to respond quickly 
to rapidly evolving epidemics.

In response to the 1997 outbreak, surveillance for influenza in poultry 
in Hong Kong has been intensified, permitting early recognition of 
outbreaks of other avian influenza strains; together with other 
preventive measures, such surveillance has helped to keep Hong Kong 
free of H5N1 in 2004. This response may serve as a model for currently 
affected countries, but wider implementation of Hong Kong's approach 
will require a global effort.

There are also strong arguments against the artificial separation of 
the people and institutions that deliver clinical care and those that 
monitor public health. We believe that uniting these structures in 
single institutions would enhance cooperation and encourage the 
interchange of information. In addition, people and countries should be 
encouraged, through reasonable compensation schemes, to report 
potential epidemics promptly and honestly.

Few countries or regions in the developed or developing world have 
responded optimally to recent epidemics and health scares. The 
continued circulation of H5N1 in poultry in Asia, with sporadic 
transmission to humans, suggests that we are far from controlling the 
current epidemic. It is probable that the next influenzavirus capable 
of causing a global pandemic will arise and spread from a developing 
country in Asia. Further investment in health care infrastructure and 
consideration of new paradigms for public health are required to 
address the emergence of such threatening diseases. Considering the 
potential death toll of a 1918-like influenza pandemic, such collective 
global investments must be a top priority.


Source Information
From the Hospital for Tropical Diseases (T.T.H.) and the Oxford 
University Clinical Research Unit, Hospital for Tropical Diseases 
(M.J., J.F.), Ho Chi Minh City, Vietnam.

References

1.  	Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and 
potentially pandemic H5N1 influenza virus in eastern Asia. Nature 
2004;430:209-213.
2.  	Chen H, Deng G, Li Z, et al. The evolution of H5N1 influenza 
viruses in ducks in southern China. Proc Natl Acad Sci U S A 
2004;101:10452-10457.
3.  	Kuiken T, Rimmelzwaan G, van Riel D, et al. Avian H5N1 influenza 
in cats. Science 2004;306:241-241.
4.  	Kobasa D, Takada A, Shinya K, et al. Enhanced virulence of 
influenza A viruses with the haemagglutinin of the 1918 pandemic virus. 
Nature 2004;431:703-707.
5.  	Tran TH, Nguyen TL, Nguyen TD, et al. Avian influenza A (H5N1) in 
10 patients in Vietnam. N Engl J Med 2004;350:1179-1188.

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