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. |