Pediatric Annals

EDITORIAL: A Pediatrician's View 

The Importance of Adenoviral Infections in Pediatrics

William A Altemeier, III, MD

Abstract

How much are you concerned about adenoviral infections? The answer is probably "not much." They exist, but they don't seem to cause many problems. Besides, we do not yet have a practical way to identify this organism in the office or an antiviral agent for treatment. However, this virus, although possessing a lower profile than most pediatric pathogens, has some characteristics that can affect practice. For one, adenovirus is the most prevalent cause of viral conjunctivitis in children.

ADENOVIRAL INFECTIONS IN GENERAL

There are more than 49 types of adenoviruses and approximately one-third are known to cause human infections that range from asymptomatic to life threatening.1'2 Upper respiratory tract infections are the most common among these, and pharyngitis is the most prominent symptom. Approximately 15% to 20% of children with isolated pharyngitis have an adenovirus infection (mostly infants and preschoolers).2 When associated with conjunctivitis and fever, the syndrome is called pharingoconjunctival fever.1,2

Adenoviral pneumonia is an uncommon complication but can be severe (10% mortality rate), and 7% to 9% of children hospitalized with acute pneumonia have an adenoviral infection.2 Adenoviral pneumonia is necrotic, and it plus influenza virus have become the leading infectious causes of bronchiectasis in the United States.

After respiratory tract infections, the second most prevalent adenovirus disease is probably gastroenteritis. Types 40 and 41 are "enteric" strains. Approximately 5% to 9% of children with acute diarrhea have this organism in their stools, but some are asymptomatic carriers so the true incidence is uncertain.2 Hemorrhagic cystitis has been caused by adenovirus types 11 and 21. So when you see a grossly hemorrhagic "sterile" urinary tract infection, bet on adenovirus. Other reported complications include myocarditis, meningoencephalomyelitis, and intussusception or a Reye's-like syndrome. Adenoviral infections can also be severe in patients who have deficient B- or T-cell immunity. Persistent pneumonia and hepatitis are problems here.

ADENOVIRAL EYE INFECTIONS

This virus can cause both conjunctivitis and keratoconjunctivitis.1"4 The former is more common in children, the latter more common in adults. Conjunctivitis alone is uncomplicated and does not usually require ophthalmologic referral, whereas keratoconjunctivitis can interfere with vision by causing corneal opacities. Adenoviral keratitis is more superficial than keratitis from herpes simplex or zoster, and thus much less likely to produce visual impairment. When adenovirus produces opacities (uncommonly), these generally resolve during months or years, but permanent visual loss is possible.

How do you know when children with conjunctivitis need to be referred because keratitis could also be present? Ideally, you would use fluorescein strips to help see a corneal ulcer (eg, the dendritic ulcer produced by herpes infections), but I bet many of you are like me and do not feel comfortable depending on this in the office, especially without a slit lamp or the skills to use one.

I would depend on any one of three key signs to indicate when I needed to refer. The first is visual impairment. Conjunctivitis does not interfere with vision and the child can see once exudates are blinked away. Second, severe corneal involvement generally produces more pain than does uncomplicated conjunctivitis. Third, uncomplicated conjunctivitis should start resolving by a week from onset. If it does not, something else may be wrong. Incidentally, one of the best ways to turn a conjunctivitis into a keratitis is to continue wearing contact lenses. Children and adolescents with significant conjunctival inflammation should switch to eyeglasses until this resolves.

SHOULD ANTIBIOTICS BE USED FOR VIRAL CONIUNCTIVITIS?

Infectious conjunctivitis almost always has a bacterial or a viral origin.1 Fungal causes are rare. The data quoted most often about etiology are from a study by Gigliotti et aL4 They cultured…

How much are you concerned about adenoviral infections? The answer is probably "not much." They exist, but they don't seem to cause many problems. Besides, we do not yet have a practical way to identify this organism in the office or an antiviral agent for treatment. However, this virus, although possessing a lower profile than most pediatric pathogens, has some characteristics that can affect practice. For one, adenovirus is the most prevalent cause of viral conjunctivitis in children.

ADENOVIRAL INFECTIONS IN GENERAL

There are more than 49 types of adenoviruses and approximately one-third are known to cause human infections that range from asymptomatic to life threatening.1'2 Upper respiratory tract infections are the most common among these, and pharyngitis is the most prominent symptom. Approximately 15% to 20% of children with isolated pharyngitis have an adenovirus infection (mostly infants and preschoolers).2 When associated with conjunctivitis and fever, the syndrome is called pharingoconjunctival fever.1,2

Adenoviral pneumonia is an uncommon complication but can be severe (10% mortality rate), and 7% to 9% of children hospitalized with acute pneumonia have an adenoviral infection.2 Adenoviral pneumonia is necrotic, and it plus influenza virus have become the leading infectious causes of bronchiectasis in the United States.

After respiratory tract infections, the second most prevalent adenovirus disease is probably gastroenteritis. Types 40 and 41 are "enteric" strains. Approximately 5% to 9% of children with acute diarrhea have this organism in their stools, but some are asymptomatic carriers so the true incidence is uncertain.2 Hemorrhagic cystitis has been caused by adenovirus types 11 and 21. So when you see a grossly hemorrhagic "sterile" urinary tract infection, bet on adenovirus. Other reported complications include myocarditis, meningoencephalomyelitis, and intussusception or a Reye's-like syndrome. Adenoviral infections can also be severe in patients who have deficient B- or T-cell immunity. Persistent pneumonia and hepatitis are problems here.

ADENOVIRAL EYE INFECTIONS

This virus can cause both conjunctivitis and keratoconjunctivitis.1"4 The former is more common in children, the latter more common in adults. Conjunctivitis alone is uncomplicated and does not usually require ophthalmologic referral, whereas keratoconjunctivitis can interfere with vision by causing corneal opacities. Adenoviral keratitis is more superficial than keratitis from herpes simplex or zoster, and thus much less likely to produce visual impairment. When adenovirus produces opacities (uncommonly), these generally resolve during months or years, but permanent visual loss is possible.

How do you know when children with conjunctivitis need to be referred because keratitis could also be present? Ideally, you would use fluorescein strips to help see a corneal ulcer (eg, the dendritic ulcer produced by herpes infections), but I bet many of you are like me and do not feel comfortable depending on this in the office, especially without a slit lamp or the skills to use one.

I would depend on any one of three key signs to indicate when I needed to refer. The first is visual impairment. Conjunctivitis does not interfere with vision and the child can see once exudates are blinked away. Second, severe corneal involvement generally produces more pain than does uncomplicated conjunctivitis. Third, uncomplicated conjunctivitis should start resolving by a week from onset. If it does not, something else may be wrong. Incidentally, one of the best ways to turn a conjunctivitis into a keratitis is to continue wearing contact lenses. Children and adolescents with significant conjunctival inflammation should switch to eyeglasses until this resolves.

SHOULD ANTIBIOTICS BE USED FOR VIRAL CONIUNCTIVITIS?

Infectious conjunctivitis almost always has a bacterial or a viral origin.1 Fungal causes are rare. The data quoted most often about etiology are from a study by Gigliotti et aL4 They cultured the eyes of 99 children with conjunctivitis and 102 age-season matched control subjects from a group practice and university clinic in Charlotte, Virginia.

Culture methods were set up to detect viruses, bacteria, chlamydia, and mycoplasma. The only two bacteria found significantly more often in the conjunctivitis group were Haemophilus influenzae (in 42% of the patients with conjunctivitis compared with 0% of the control subjects) and Streptococcus pneumoniae (in 12% of the patients with conjunctivitis compared with 3% of the control subjects). Adenovirus was isolated from the eyes of 20% of the patients with conjunctivitis and 0% of the control subjects. No other pathogens were found to be significantly associated with conjunctivitis in this study. One of these three agents was responsible for 72% of the conjunctivitis in these subjects, who were beyond the neonatal period.4 Herpes simplex and zoster and enteroviruses can cause conjunctivitis (and keratitis), but adenovirus leads by a wide margin.1"5

So antibiotics are not necessary if you know that the conjunctival infection is viral instead of bacterial. But how easy is this to discern? You can make an educated guess, but Gigliotti et al. demonstrated that you cannot be certain without cultures4 and of course it takes more than a day to get an answer this way.

For example, they noted that a purulent exudate was present in 93% of the children with H. influenzae, 83% of the children with S. pneumoniae, and 45% of the children with adenoviral infections. As mentioned previously, concurrent pharyngitis and fever are found in adenoviral pharyngoconjunctival fever. And "conjunctivitis-otitis" is characteristic of H. influenzae. But pharyngitis was found in 5% of H. influenzae infections, 8% of pneumococcal infections, and 55% of adenovirus conjunctival infections, and otitis media occurred in 33% of H. influenzae infections, 8% of pneumococcal infections, and 10% of adenovirus conjunctival infections.4 Many pediatricians prescribe antibiotic drops for patients with acute infectious conjunctivitis without counting on being able to distinguish a viral from a bacterial etiology.3,4

Adenoviral conjunctivitis and keratoconjunctivitis have one more important characteristic - they are highly contagious.1'3 Virus shedding persists for up to 2 weeks after symptoms begin and the organism can remain infectious for as long as a week out of the body. It is transmissible to the eyes or respiratory tract by hands or fomites (eg, medical instruments) and by droplets. Epidemics have been reported from swimming pools and in nursing homes, summer camps, military units, hospitals (including neonatal intensive care units), and physicians' offices, especially ophthalmology clinics. So it is important to wear gloves when examining or even shaking hands with patients.

What does this mean to your office? It is important to prevent spreading this among and to patients. The Red Book recommends that a health care worker who develops or is suspected of having viral conjunctivitis not have patient contact for 2 weeks after the onset of disease in the second eye.1 One could argue that, if these infections are so common, why take special precautions to prevent their spread? For example, the Red Book allows school-aged children with viral or bacterial conjunctivitis to continue attending school after starting the indicated therapy unless there are systemic signs of illness.5

But you still can't have an epidemic originating from your office, and you should be able to recognize an epidemic and know how to intervene. Swimming pool epidemics have been associated with the malfunction of chlorination systems.1 And not all of these infections are benign, especially for adults. So these are some of the characteristics of adenovirus that relate to pediatric practice.

REFERENCES

1. American Academy of Pediatrics. Summaries of infectious diseases: adenovirus infections. In: Pickering LK, ed. 2000 Red Book: Report of the Committee on Infectious Diseases, 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000:162-163.

2. Mcintosh K. Adenovirus. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson's Textbook of Pediatrics, 16th ed. Philadelphia: W. B. Saunders; 2000:994-995.

3. Leibowitz HM. The red eye. N Engl J Med. 2000343:345-351.

4. Giglioni F, Williams WT, Hayden FG, et al. Etiology of acute conjunctivitis in children. J Pediatr. 1981 ,"98: 531-536.

5. American Academy of Pediatrics. Summaries of infectious diseases: school health. In: Pickering LK, ed. 2000 Red Book: Report of the Committee on Infectious Diseases, 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000:123.

10.3928/0090-4481-20010801-03

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