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Review of 1918 Pandemic Flu
Studies Offers More Questions than Answers
Experts Say Further Study of Past
Pandemics Key to Preparedness
Scientists and public health
officials, wary that the H5N1 avian influenza virus could trigger an
influenza pandemic, have looked to past pandemics, including the 1918
“Spanish Flu,” for insight into pandemic planning. However, in a Journal of
Infectious Diseases review article now posted online, David M. Morens, M.D.,
and Anthony S. Fauci, M.D., of the National Institute of Allergy and
Infectious Diseases (NIAID), part of the National Institutes of Health,
conclude that studies of the 1918 influenza pandemic, which killed some 50 to
100 million people around the globe, have so far raised more questions than
they answer.
“Today, nearly a century after the
1918 influenza pandemic, its mysteries remain largely unexplained,” says Dr.
Fauci, NIAID director. “Much work remains to be done, by scientists as well
as by historians and other scholars, with regard to the many unanswered
questions surrounding this historic pandemic. These studies must be part of
our preparedness efforts as we face the prospect of a future influenza
pandemic.”
Dr. Morens adds, “In addition to
ongoing laboratory studies, we feel that much can be learned from examining
the vast scientific literature related to the 1918 influenza pandemic and
previous influenza pandemics. A treasure trove of journal articles and other
materials exists in many languages that can be mined for novel information
with practical applications relevant to the threat of pandemic influenza we
face.”
In their article, Drs. Morens and
Fauci review several topics, including the origins of the 1918 pandemic
influenza virus, the excess mortality of the pandemic, the predilection to
kill the young and healthy, the lower-than-expected mortality among the
elderly, and the cyclicity of influenza pandemics over the past 100 years.
Such topics are relevant today as highly pathogenic H5N1 avian influenza
viruses have spread from Asia to the Middle East, Europe and Africa.
One of the great unsolved
mysteries surrounding the 1918 pandemic is why it tended to kill the young
and healthy. Unlike yearly influenza epidemics, in which death rates are
highest among infants, the elderly and those with chronic health conditions,
the 1918 influenza pandemic took its greatest toll on healthy adults between
the ages of 20 and 40. One possible explanation, supported by recent studies
in mice with a reconstructed version of the 1918 virus, is that an
over-responsive immune system may release a “cytokine storm,” or excessive
amount of immune system proteins that trigger inflammation and harm the patient
in the process. Of note, most deaths among humans infected with the H5N1
avian influenza virus have occurred in individuals under the age of 40.
However, as the authors point out, it is not yet known whether there is a
higher percentage of young people in the affected populations compared to
older people, whether younger people are more susceptible to infection or
whether they have more exposure to infected birds.
Highly pathogenic H5N1 influenza
viruses have primarily infected wild birds and domestic poultry populations
in dozens of countries, although at least 275 people have been infected and
167 have died. As Drs. Morens and Fauci point out, the H1N1 virus that caused
the 1918 pandemic appears to be avian in origin, but the host source of the
1918 virus has never been identified. Furthermore, no major disease outbreaks
among birds were documented immediately before the 1918 pandemic. They
suggest that an avian influenza strain could have been hidden in an obscure
ecological niche, and the pandemic strain arose by the genetic adaptation of
that avian virus to a new human host.
“The more we learn about influenza
A viruses and what they can do to maintain their deadly relationship with the
human species, the more remarkable they seem,” says Dr. Morens. “The
challenge for us is to learn as much about influenza viruses as they have
already ‘learned’ about us.”
Drs. Morens and Fauci also discuss
the high number of deaths associated with the 1918 pandemic and the disease
process, based on clinical and autopsy studies published between 1918 and
1922. Most pandemic deaths were associated with either an aggressive
bronchopneumonia, in which bacteria could be cultivated from lung tissue at
autopsy, or with a severe acute respiratory distress-like syndrome (ARDS) characterized
by blue-grey facial discoloration and excessive fluid in the lungs. In
neither case is it known whether most deaths were caused by a secondary
bacterial infection or a primary viral infection. They propose that the many
excess deaths that occurred during the 1918 influenza pandemic resulted from
a disease process that began with a severe acute viral infection that spread
down the respiratory tree causing severe tissue damage, which was often
followed by secondary bacterial invasion. More definitive answers regarding
the causes of deaths due to the “Spanish Flu” may require a comprehensive
re-examination of the 1918 autopsy series, they note.
If a pandemic with similar
characteristics were to occur in the near future, Drs. Morens and Fauci
predict that the relative number of deaths would be substantially lower than
that which occurred in 1918.
“Almost all ‘then-versus now’
comparisons in theory are encouraging,” they write. “In 2007 public health is
much more advanced, with better prevention knowledge, good influenza
surveillance, more trained personnel at all levels, well-established
prevention programs featuring annual vaccination with up-to-date influenza
and pneumococcal vaccines, and a national and international prevention
infrastructure.” In addition, two classes of antiviral drugs are currently
available, as well as antibiotics effective against bacteria that cause
influenza-associated pneumonia.
The most difficult challenge in
mitigating the effects of a severe pandemic today would be to ensure access
to medical care and resources, they note. Hospitals, medical personnel and
drug suppliers could be overwhelmed with huge demands for services, medicines
and vaccines, a situation that would be exacerbated in less developed
countries and impoverished regions.
Drs. Fauci and Morens conclude
that the best hope for the future lies in developing and stockpiling more
broadly protective influenza vaccines. In the meantime, prevention efforts
should be directed towards logistical planning, increased surveillance, the
development of medical countermeasures, an improved understanding of pandemic
risks, and an aggressive and broad research agenda.
NIAID is a component of the
National Institutes of Health. NIAID supports basic and applied research to
prevent, diagnose and treat infectious diseases such as HIV/AIDS and other
sexually transmitted infections, influenza, tuberculosis, malaria and illness
from potential agents of bioterrorism. NIAID also supports research on basic
immunology, transplantation and immune-related disorders, including
autoimmune diseases, asthma and allergies. News releases, fact sheets and
other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health
(NIH) — The Nation's Medical Research Agency — includes 27 Institutes
and Centers and is a component of the U.S. Department of Health and Human
Services. It is the primary federal agency for conducting and supporting
basic, clinical and translational medical research, and it investigates the
causes, treatments, and cures for both common and rare diseases. For more
information about NIH and its programs, visit www.nih.gov.
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Reference: DM Morens et al. The 1918
influenza pandemic: Insights for the 21st century. The Journal of Infectious
Diseases. DOI: 10.1086/511989 (2007).
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