Acute diarrheal disease in young children is a major cause of morbidity world wide and is a leading cause of
mortality in developing countries. Research has shown that enteric adenoviruses, primarily Ad40 and Ad41,
are a leading cause of diarrhea in many of these children, second only to the rotaviruses. However many
different symptoms can manifest, depending on the type of infecting Adenovirus. There are 49 distinct
serotypes that can cause infections in humans.

Adenoviruses were first discovered in human adenoids (tonsils), in 1953. There are over 50 different
Adenovirus serotypes in humans, and they are responsible for 5-10% of upper respiratory infections in
children, and many infections in adults as well. Infections are most likely to occur in people living in
institutional conditions such as military bunkers.

Adenoviruses are primarily transmitted by droplets coughed-out by sick people. It can also be transmitted by
contact with an infected person, fecal residue, or by virus particles left on objects that an infected person
touches.

The diarrhea resulting from enteric adenoviruses is longer in duration than that caused by the rotaviruses,
usually lasting 7 - 8 days. Adenovirus infections often show up as conjunctivitis, tonsilitis (which may look
exactly like strep throat and cannot be distinguished from strep except by throat culture), an ear infection, or
croup. Adenoviruses can also cause gastroenteritis (stomach flu). A combination of conjunctivitis and tonsilitis
is particularly common with adenovirus infections. Small children are especially prone to develop adenovirus
bronchiolitis or pneumonia, both of which can be severe. In babies, adenoviruses can also cause coughing
fits that are almost exactly like whooping cough. Adenoviruses can also lead to viral meningitis or
encephalitis. Rarely, adenovirus causes inflammation of the urinary bladder -- also known as cystitis,
producing blood in the urine. In children, adenoviruses may cause acute upper respiratory infections with
fever and runny nose. Adenovirus types 1, 2, 3,5, and 6 are responsible for most of these infections.

Adenovirus can be the root of a wide range of symptoms such as:

Colds
Pharyngitis (sore throat)
Bronchitis
Pneumonia
Diarrhea
Conjunctivitis (eye infection)
Fever
Cystitis (bladder inflammation or infection)
Rash illness
Neurologic disease
Ear infection

One type of illness called Lytic adenovirus infection destroys large numbers of cells, in which healthy cells
are killed and used to replicate up to one million new viruses per cell killed (of which 1-5% are infectious). In
chronic or latent infection, a much smaller number of the virus replicate and healthy cells can multiply more
rapidly than they are destroyed. People who have this kind of infection don't seem to be sick. This is probably
why many adults have immunity to adenoviruses without realizing they have ever been infected.

Some people with adenovirus gastroenteritis may release the virus in their stools for months after the
symptoms are gone. The virus can even be passed from person to person by contact with water in swimming
pools that do not have enough chlorine in them to kill the virus. As with many other infectious organisms,
proper hand-washing is one way to lessen the spread of adenoviruses from one person to another. Heat and
bleach will kill adenovirus on objects.

The majority of people infected with Adenovirus recover on their own. People with immune-system
deficiencies sometimes die of adenovirus infections, but very rarely do previously healthy people die of these
infections.

Military Experience with Adenovirus

Adenovirus thrives in crowded areas such as military barracks, and is common in those with weakened
immune systems. Overstressed recruits, training to get in shape and adapt to the military, are ideal
incubators for the virus.

An mass outbreak affected many bases during the 1950's and 1960's. An undisclosed number of troops died
from this outbreak. However an applied vaccine in 1971 halted new infections. So successful was the vaccine
that the virus was forgotten, as new personnel took up positions in the military. However doctors warned that
the Adenovirus was controlled, not eliminated. Yet the vaccine ceased to be a high priority and when funds
dried up, vaccine production stopped in 1996. Officials claimed that there had been no outbreaks since 1987,
so a 'wait-and-see' strategy was adopted.

Seven weeks later, on May 22, 1997, the first feverish soldier dragged himself into Fort Jackson, S.C medical
center, in the largest basic training center on U.S soil. About a month later, over 70 hospitalizations were
occurring weekly with over 650 confirmed cases of Adenovirus infection.

Thankfully, several concerned doctors had already established a system to track the reemergence of
Adenovirus in the military. Infections continued until stockpiles were shipped to bases and treatments
distributed. It took 7 months to successfully halt this outbreak.

Another outbreak at Lackland base occurred in October of 1999 during it's challenging first "Warrior Week".
Over 1,000 recruits were infected over the course of 8 months until vaccine pills were available.

Within 3 months in 2000, the virus killed 2 young recruits; the first to die in 28 years. The first victim
developed a fever June 20 and sought medical treatment then returned to his barracks. When symptoms
remained unabated, he revisited the clinic June 23 and was given an antibiotic for assumed bronchitis. On
June 24 he was discovered unconscious in the barracks. He never resumed consciousness and died July 3,
according to reports from the CDC.

The second victim was from the same training center in the Great Lakes area. The 18-year-old recruit had
gone to the medical clinic three times complaining of respiratory difficulties, and had been given a
decongestant and acetaminophen. On September 18, 2000, he went back a fourth time, suffering from
severe indigestion, severe weakness and a purplish rash on his legs, suggesting hemorrhaging. He died nine
hours later, according to CDC records.

The November 16, 2007 issue of the Morbidity and Mortality Weekly Report noted an unusual number of
recent cases of severe pneumonia and deaths caused by adenovirus serotype 14 (AD14) infection among
civilian and military communities in the U.S. This strain of AD14 seems to have a particularly high rate of
severe illness in humans, but it's occurrence has been unusual. Anyway, health departments should monitor
outbreaks or clusters of AD14 infection.

Spurred by the highly publicized deaths and the rising infection rates, the Defense Department signed a
$35.4 million contract with a biotechnology company in September 2001. Yet the latest vaccine will not be
finalized until at least 2007, with a release tentatively scheduled in 2009. The lengthy process is due to
clinical trial requirements, even though the vaccine is not much different than the last one.

A total of 6 deaths have since been associated with Adenovirus, but most information about them have been
keep secretive by the military such as the names.

Most people have been infected by at least one adenovirus serotype by the time they reach school age. As
adults most people have acquired immunity to multiple adenovirus types due to the exposure they had as
children. In developing countries, babies who contract the virus and get diarrhea may die within 24 hours of
dehydration, especially if clean water and medical treatment isn't immediately available.

Infection is usually self-limiting in people with healthy immune systems, but accurate and rapid diagnosis can
eliminate the need for expensive and invasive tests. An ELISA test using specific antibodies have been
shown to be a sensitive, accurate and rapid method of diagnosis.

As with most viruses, there are no antibiotics that help cure an adenoviral infection, so treatment is largely
directed at the symptoms.

IVD Research, Inc.
5909 Sea Lion Place Suite D
Carlsbad, California  92010  USA
Phone: (760) 929-7744
Fax: (760) 431-7759
Email:
orders@ivdreasearch.com
ivd@ivdresearch.com