NIAID Experts See Dengue as Potential Threat
to U.S. Public Health
A disease most Americans have never heard of could soon become
more prevalent if dengue, a flu-like illness that can turn deadly,
continues to expand into temperate climates and increase in severity,
according to a new commentary by Anthony S. Fauci, M.D., director
of the National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health, and David M. Morens,
M.D., Fauci's senior scientific advisor. Their commentary appears
in the January 9 and 16 double issue of the Journal of the
American Medical Association.
Previously confined to tropical and subtropical climates, the
mosquito-borne illness is becoming a much more serious problem
along the U.S.-Mexico border and in the commonwealth of Puerto
Rico. Dengue occurs sporadically and has had a relatively small
impact on the United States thus far, so the amount of dengue-related
illness in this country is presently minimal. However, the disease
tends to occur in explosive epidemics. Moreover, the NIAID scientists
note, efforts to control the populations of mosquitoes that transmit
dengue have fallen short of their goal.
These trends stimulated Drs. Fauci and Morens to call for more
research to understand and combat dengue. "Widespread appearance
of dengue in the continental United States is a real possibility," the
NIAID scientists write in their commentary. "Worldwide, dengue
is among the most important reemerging infectious diseases with
an estimated 50 to 100 million annual cases...[and] 22,000 deaths." Public
health officials need to take the threat seriously, the scientists
assert, because no specific treatments or vaccines for dengue are
available. To fight the disease, they state, "The formidable
challenges of understanding dengue pathogenesis and of developing
effective therapies and vaccines must be met."
Dengue (pronounced "DENG-ee") is caused by any of four
related viruses transmitted to humans by the mosquitoes Aedes
albopictus (nicknamed "Asian tiger mosquito") and Aedes
aegypti. First seen in the United States in 1985, Ae.
albopictus has been found in 36 states, while Ae. aegypti has
been found in several southern states. Experience elsewhere in
the world shows that where these mosquitoes go, the disease usually
follows.
In their commentary, Drs. Fauci and Morens provide a historical
and clinical overview of dengue; discuss the controversy about
the origins and development of the most severe forms of the disease;
describe the implications of dengue pathogenesis for safe vaccination
strategies; and note the challenges to dengue treatment, control
and prevention. The scientists highlight the hypothesis that naturally
and maternally acquired dengue antibody may precipitate severe
disease on subsequent infection. This hypothesis has implications
for dengue vaccine development, the authors write, because a vaccine
could potentially stimulate the immune system to cause more severe
disease on subsequent natural infection.
Most people infected with a dengue virus have no symptoms or a
mild fever. Those who do get sick sometimes experience minor bleeding,
such as from the nose or gums, and frequently develop a high fever,
severe headache, pain behind the eyes and in joints and muscles,
and a rash. Sometimes the disease leads to leakage of blood plasma
out of the circulatory system and into tissues, causing blood pressure
to drop. This condition often can be reversed by giving patients
fluids and electrolytes. With proper treatment, case fatality rates
for severe dengue can be less than 1 percent. If left untreated,
however, the person may become unresponsive, slip into a coma and
possibly die. Early diagnosis and treatment of dengue are critical
to preventing shock and death. The severe forms of dengue disease
have been defined by the World Health Organization as dengue hemorrhagic
fever (DHF) and dengue shock syndrome (DSS).
Recognizing the threat to public health posed by dengue, NIAID
allocated $33.2 million in fiscal year 2007 for nearly 60 dengue
research projects, including basic research on dengue, DHF and
DSS; projects to develop vaccines, diagnostics and therapeutics
for the disease; and clinical trials of vaccines.
The priorities of NIAID's dengue research program include the
following:
- Develop animal models to study the basic mechanisms of infection
and perform preliminary tests of vaccines and therapeutics
- Design and evaluate vaccines and therapeutics
- Understand how dengue viruses can elicit antibodies — normally
a form of protection against disease — that may help the
viruses infect host cells and exacerbate the disease
- Learn what causes capillaries to leak plasma in DHF and DSS
- Understand the genetic factors in both people and dengue viruses
that influence the severity of the disease
- Identify biological markers that might predict whether an individual
is protected from dengue viruses and whether a person with dengue
fever will likely develop DHF or DSS
By vigorously pursuing these research priorities, NIAID hopes
to advance the development of medical tools to fight this important
reemerging infectious disease.
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.
Reference:
DM Morens and AS Fauci. Dengue and hemorrhagic fever: A potential
threat to public health in the United States. JAMA DOI:10.1001/jama.299.2.214
(2007).
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