Adenovirus infections

Definition

Adenoviruses are small infectious agents that cause upper respiratory tract infections, conjunctivitis , and other infections in humans.

Description

Adenoviruses were discovered in 1953. By 2004 about 49 different types had been identified, and about half of those were believed to cause human diseases. Adenovirus infections can occur throughout the year, unlike the seasonality associated with other respiratory viruses.

In children, adenoviruses most often 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. Occasionally more serious lower respiratory diseases, such as pneumonia or bronchitis , may occur. Adenoviruses can also cause acute diarrhea in young children, characterized by fever and watery stools. This condition is caused by adenovirus types 40 and 41 and can last as long as two weeks.

As much as 51 percent of all hemorrhagic cystitis (inflammation of the bladder and of the tubes that carry urine to the bladder from the kidneys) in American and Japanese children can be attributed to adenovirus infection. A child who has hemorrhagic cystitis has bloody urine for about three days, and invisible traces of blood can be found in the urine a few days longer. The child will feel the urge to urinate frequently but find it difficult to do so, for about the same length of time.

Other illnesses associated with adenovirus include:

• encephalitis (inflammation of the brain) and other infections of the central nervous system (CNS)
• gastroenteritis (inflammation of the stomach and intestines), which sometimes leads to enlarged lymph nodes in the intestines and rarely intussusception
• acute pharyngoconjunctival fever (inflammation of the lining of the eye [conjunctivitis] with fever)
• acute mesenteric lymphadenitis (inflammation of lymph glands in the abdomen)
• chronic interstitial fibrosis (abnormal growth of connective tissue between cells)
• intussusception (a type of intestinal obstruction)
• pneumonia that does not respond to antibiotic therapy
• whooping cough syndrome when Bordetella pertussis (the bacterium that causes classic whooping cough) is not found

Transmission

Specific adenovirus infections can be traced to particular sources and produce distinctive symptoms. In general, however, adenovirus infection is transmitted by the following:

• inhaling airborne viruses
• getting the virus in the eyes by swimming in contaminated water, using contaminated eye solutions or instruments, wiping the eyes with contaminated towels, or rubbing the eyes with contaminated fingers
• not washing the hands after using the bathroom and then touching the mouth or eyes

Infections often occur in situations in which individuals are in close contact with one another, such as the military, cruise ships, or college dormitories. Outbreaks among children are frequently reported at boarding schools and summer camps.

Most children have been infected by at least one adenovirus by the time they reach school age. Most adults have acquired immunity to multiple adenovirus types due to infections they had as children.

Demographics

Adenoviruses are responsible for 3 to 5 percent of acute respiratory infections in children. Most adenovirus infections occur between the ages of six months and five years. The incidence of adenovirus infection does not appear to differ among males and females or individuals of different race.

Causes and symptoms

In one mode of adenovirus infection (called lytic infection because it destroys large numbers of cells), adenoviruses kill healthy cells and replicate up to 1 million new viruses per cell killed, of which 1 to 5 percent are infectious. People with this kind of infection feel sick. In chronic or latent infection, a much smaller number of viruses are released, and healthy cells can multiply more rapidly than they are destroyed. People who have this kind of infection do not exhibit symptoms.

Children who have normal immune systems usually experience only minor symptoms when infected with adenovirus. The course of infection tends to be more serious in children who are immunocompromised, such as those undergoing chemotherapy or those who have a disease that disrupts normal immune response (e.g. human immunodeficiency syndrome [HIV]). In such children, the virus more often affects organs such as the lungs, liver, and kidneys, and the risk of fatality increases.

Symptoms common to respiratory illnesses caused by adenovirus infection include cough, fever, runny nose, sore throat , and watery eyes. In children with gastroenteritis caused by the adenovirus, symptoms may include diarrhea, fever, nausea, vomiting , and respiratory symptoms. Children with acute pharyngoconjunctival fever usually show signs of conjunctivitis, fever, sore throat, runny nose, and inflammation of the lymph glands in the neck (certical adenitis). More rarely, if the virus infects the lining of the brain and spinal cord (meninges) or the brain itself, meningitis or encephalitis may result; symptoms include fever, stiff or painful neck, irritability, changes in personality, or seizures.

When to call the doctor

Parents should contact a healthcare provider if the following applies to the infected child:

• The child is under three months of age.
• The child has symptoms that continue to worsen after one week.
• The child has difficulty breathing.
• The child shows symptoms of meningitis or encephalitis.
• The child has eye redness and swelling that becomes painful.
• The child shows signs of infection and is immunocompromised.

Diagnosis

Although symptoms may suggest the presence of adenovirus, distinguishing these infections from other viruses can be difficult. A definitive diagnosis is based on culture or detection of the virus in eye secretions, sputum, urine, or stool.

The extent of infection can be estimated from the results of blood tests that measure increases in the quantity of antibodies the immune system produces to fight it. Antibody levels begin to rise about a week after infection occurs and remain elevated for about a year.

Treatment

Treatment of adenovirus infections is usually supportive and aimed at relieving symptoms of the illness. Bed rest may be recommended along with medications to reduce fever and/or pain . (Aspirin should not be given to children because it is associated with Reye's syndrome.) Eye infections may benefit from topical corticosteroids to relieve symptoms and shorten the course of the disease. Hospitalization is usually required for severe pneumonia in infants and for keratoconjunctivitis (to prevent blindness). No effective antiviral drugs had been developed as of 2004.

Nutritional concerns

Because a child can become easily dehydrated if suffering from vomiting or diarrhea, it is important care-givers provide adequate fluid intake. Fluids such as water, breast milk or formula (if applicable), electrolyte replacement drinks, diluted juice, or clear broths should be encouraged. Drinks with caffeine should be avoided because of caffeine's diuretic effects (i.e. causes water to be lost through urine).

Prognosis

In otherwise healthy children, adenovirus infections are rarely fatal, and most patients recover fully. Immunocompromised children have a greater chance of serious side effects and death, with fatality rates as high as 50 to 69 percent (depending on the cause and extent of immunodeficiency).

Prevention

Practicing good personal hygiene and avoiding contact with people with infectious illnesses can reduce the risk of developing adenovirus infection. Proper hand washing can prevent the spread of the virus by oral-fecal transmission. Sterilization of instruments and solutions used in the eye can help prevent the spread of EKC, as can adequate chlorination of swimming pools.

A vaccine containing live adenovirus types 4 and 7 has been used to control disease in military recruits, but it is not recommended or available for civilian use. A recent resurgence of the adenovirus was found in a military population as soon as the vaccination program was halted. Vaccines prepared from purified subunits of adenovirus were as of 2004 under investigation.

Parental concerns

In the home setting, frequent hand washing should be encouraged, and children's toys and shared belongings should be frequently cleaned. Children who suffer from adenovirus infection should be kept home from school or daycare until they no longer show symptoms.

KEY TERMS

Conjunctivitis —Inflammation of the conjunctiva, the mucous membrane covering the white part of the eye (sclera) and lining the inside of the eyelids also called pinkeye.

Reye's syndrome —A serious, life-threatening illness in children, usually developing after a bout of flu or chickenpox, and often associated with the use of aspirin. Symptoms include uncontrollable vomiting, often with lethargy, memory loss, disorientation, or delirium. Swelling of the brain may cause seizures, coma, and in severe cases, death.

Virus —A small infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein. A virus needs a living cell to reproduce.

Whooping cough —An infectious disease of the respiratory tract caused by a bacterium, Bordetella pertussis. Also known as pertussis.

Resources

BOOKS

Demmler, Gail J. "Adenoviruses." In Principles and Practice of Pediatric Infectious Diseases. Edited by Sarah S. Long. New York: Churchill Livingstone, 2003.

Treanor, John J., and Frederick G. Hayden. "Adenovirus." Textbook of Respiratory Medicine. Edited by John F. Murray and Jay A. Nadel. Philadelphia: Saunders, 2000.

PERIODICALS

Evans, Jeff. "Viral Gastroenteritis On Board." Internal Medicine News (January 15, 2003): 44.

"Guard against Pertussis." Contemporary Pediatrics (February 2003): 87.

ORGANIZATIONS

American Academy of Pediatrics. 141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098. Web site: <www.aap.org>.

National Center for Infectious Diseases, Center for Disease Control and Prevention. Mailstop C-14, 1600 Clifton Rd., Atlanta, GA 30333. Web site: <www.cdc.gov/ncidod>.

WEB SITES

"Adenoviruses." Centers for Disease Control and Prevention, Respiratory and Enteric Viruses Branch, August 11, 2003. Available online at <www.cdc.gov/ncidod/dvrd/revb/respiratory/eadfeat.htm> (accessed December 23, 2004).

Gompf, Sandra G., and Wendy Carter. "Adenoviruses." eMedicine, July 19, 2004. Available online at <www.emedicine.com/med/topic57.htm> (accessed December 23, 2004).

Maureen Haggerty Teresa G. Odle Stephanie Dionne Sherk

Adenovirus Infections

Definition

Adenoviruses are DNA viruses (small infectious agents) that cause upper respiratory tract infections, conjunctivitis, and other infections in humans.

Description

Adenoviruses were discovered in 1953. About 47 different types have been identified since then, and about half of them are believed to cause human diseases. Infants and children are most commonly affected by adenoviruses. Adenovirus infections can occur throughout the year, but seem to be most common from fall to spring.

Adenoviruses are responsible for 3-5% of acute respiratory infections in children and 2% of respiratory illnesses in civilian adults. They are more apt to cause infection among military recruits and other young people who live in institutional environments. Outbreaks among children are frequently reported at boarding schools and summer camps. Another example includes an increased outbreak of gastroenteritis among cruise passengers in 2002.

Acquired immunity

Most children have been infected by at least one adenovirus by the time they reach school age. Most adults have acquired immunity to multiple adenovirus types due to infections they had as children.

In one mode of adenovirus infection (called lytic infection because it destroys large numbers of cells), adenoviruses kill healthy cells and replicate up to one million new viruses per cell killed (of which 1-5% are infectious). People with this kind of infection feel sick. In chronic or latent infection, a much smaller number of viruses are released 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 been infected.

Childhood infections

In children, adenoviruses most often 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. Occasionally more serious lower respiratory diseases, such as pneumonia, may occur.

Adenoviruses also cause acute pharyngoconjunctival fever in children. This disease is most often caused by types 3 and 7. Symptoms, which appear suddenly and usually disappear in less than a week, include:

• inflammation of the lining of the eyelid (conjunctivitis)
• fever
• sore throat (pharyngitis)
• runny nose
• inflammation of lymph glands in the neck (cervical adenitis)

Adenoviruses also cause acute diarrhea in young children, characterized by fever and watery stools. This condition is caused by adenovirus types 40 and 41 and can last as long as two weeks.

As much as 51% of all hemorrhagic cystitis (inflammation of the bladder and of the tubes that carry urine to the bladder from the kidneys) in American and Japanese children can be attributed to adenovirus infection. A child who has hemorrhagic cystitis has bloody urine for about three days, and invisible traces of blood can be found in the urine a few days longer. The child will feel the urge to urinate frequently—but find it difficult to do so—for about the same length of time.

Adult infections

In adults, the most frequently reported adenovirus infection is acute respiratory disease (ARD, caused by types 4 and 7) in military recruits. Influenza-like symptoms including fever, sore throat, runny nose, and cough are almost always present; weakness, chills, headache, and swollen lymph glands in the neck also may occur. The symptoms typically last three to five days.

Epidemic keratoconjunctivitis (EKC, caused by adenovirus types 8, 19, and 37) was first seen in shipyard workers whose eyes had been slightly injured by chips of rust or paint. This inflammation of tissues lining the eyelid and covering the front of the eyeball also can be caused by using contaminated contact lens solutions or by drying the hands or face with a towel used by someone who has this infection.

KEY TERMS

Conjunctivitis— Inflammation of the conjunctiva, the mucous membrane lining the inner surfaces of the eyelid and the front of the eyeball.

Virus— A small infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein.

The inflamed, sticky eyelids characteristic of conjunctivitis develop 4-24 days after exposure and last between one and four weeks. Only 5-8% of patients with epidemic keratoconjunctivitis experience respiratory symptoms. One or both eyes may be affected. As symptoms of conjunctivitis subside, eye pain and watering and blurred vision develop. These symptoms of keratitis may last for several months, and about 10% of these infections spread to at least one other member of the patient's household.

Other illnesses associated with adenovirus include:

• encephalitis (inflammation of the brain) and other infections of the central nervous system (CNS)
• gastroenteritis (inflammation of the stomach and intestines)
• acute mesenteric lymphadenitis (inflammation of lymph glands in the abdomen)
• chronic interstitial fibrosis (abnormal growth of connective tissue between cells)
• intussusception (a type of intestinal obstruction)
• pneumonia that doesn't respond to antibiotic therapy
• whooping cough syndrome when Bordetella pertussis (the bacterium that causes classic whooping cough) is not found

Causes and symptoms

Specific adenovirus infections can be traced to particular sources and produce distinctive symptoms. In general, however, adenovirus infection is caused by:

• inhaling airborne viruses
• getting the virus in the eyes by swimming in contaminated water, using contaminated eye solutions or instruments, wiping the eyes with contaminated towels, or rubbing the eyes with contaminated fingers.
• not washing the hands after using the bathroom, and then touching the mouth or eyes

Symptoms common to most types of adenovirus infections include:

• cough
• fever
• runny nose
• sore throat
• watery eyes

Diagnosis

Although symptoms may suggest the presence of adenovirus, distinguishing these infections from other viruses can be difficult. A definitive diagnosis is based on culture or detection of the virus in eye secretions, sputum, urine, or stool.

The extent of infection can be estimated from the results of blood tests that measure increases in the quantity of antibodies the immune system produces to fight it. Antibody levels begin to rise about a week after infection occurs and remain elevated for about a year.

Treatment

Treatment of adenovirus infections is usually supportive and aimed at relieving symptoms of the illness. Bed rest may be recommended along with medications to reduce fever and/or pain. (Aspirin should not be given to children because of concerns about Reye's syndrome.) Eye infections may benefit from topical corticosteroids to relieve symptoms and shorten the course of the disease. Hospitalization is usually required for severe pneumonia in infants and for EKC (to prevent blindness). No effective antiviral drugs have been developed.

Prognosis

Adenovirus infections are rarely fatal. Most patients recover fully.

Prevention

Practicing good personal hygiene and avoiding people with infectious illnesses can reduce the risk of developing adenovirus infection. Proper hand-washing can prevent the spread of the virus by oral-fecal transmission. Sterilization of instruments and solutions used in the eye can prevent the spread of EKC, as can adequate chlorination of swimming pools.

A vaccine for pertussis has been developed and is in use in combination with diphtheria and tetanus vaccines for infants. It is shown to have nearly 90% efficacy. A vaccine containing live adenovirus types 4 and 7 is used to control disease in military recruits, but it is not recommended or available for civilian use. A recent resurgence of the adenovirus was found in a military population as soon as the vaccination program was halted. Vaccines prepared from purified subunits of adenovirus are under investigation.

Resources

PERIODICALS

Evans, Jeff. "Viral Gastroenteritis On Board." Internal Medicine News (January 15, 2003): 44.

"Guard Against Pertussis." Contemporary Pediatrics (February 2003): 87.

Kolavic-Gray, Shellie A., et al. "Large Epidemic of Adenovirus Type 4 Infection Among Military Trainees: Epidemiological, Clinical, and Laboratory Studies." Clinical Infectious Diseases (October 1, 2002): 808-811.