Adenoviruses

00:01 Adenoiridae; viruses.

00:04 The adenoviruses are nonenveloped viruses which have an icosahedral capsid.

00:10 Important to remember about the adenoviruses is that they are a group which contain double-stranded DNA in a linear or a straight genome.

00:20 The adenoviruses are transmitted pretty much any way you can imagine.

00:25 Through respiratory aerosols, through fecal-oral contact, through fomites, i.e., little toys that we love to play with with our children, close contact, far contact, you name it, and as a very special gift, in inadequately chlorinated swimming pools.

00:41 As anybody has been to a municipal pool knows, you can sometimes get pink eye, one of our diseases from adenovirus.

00:50 How does adenovirus cause its pathogenesis? It has fibers from its surrounding capsid that bind to specific cell receptors and insert the adenovirus into the cell to begin its growth process.

01:05 In addition, it contains growth- suppressing proteins, but it a way to inhibit those, so that its host cell not only lives until it's done being used by the adenovirus, but if anything, proliferates.

01:19 and grows even better, which is another way of sort of progressing the adenovirus' impact on that local area.

01:27 Once adenovirus is ready to leave, it's already replicated itself, it's created multiple additional variants, then it lyses the host cell And it's only when that lysis occurs, that rupture of the host cell, that inflammation from the human immune system can begin.

01:45 Where it begins depends on where the adenovirus is bound.

01:49 And you'll note that I did not name a specific target cell.

01:52 That's because there are many different types of adenovirus, each of which have different tropism, different focus on the part of the body which they will attack.

02:02 So, one might have a respiratory-based adenovirus, in which case, lysis at the cell creates respiratory disease.

02:10 Similarly, something in the gastrointestinal tract, the conjunctiva, the cornea -- you get the picture.

02:17 Some adenovirus, however, are able to create a persistent or a latent infection, meaning that they can chronically infect their host cells, specifically in the lymphoid tissues without ysing the host cell, without creating that immune reaction.

02:33 That means, though, that they can react -- interact and reactivate at any point that they're sort of triggered to do so.

02:40 And then, they might develop viremia, entering the virus into the bloodstream within like a systemic adenovirus infection.

02:49 So let's now look, in comparison, at some of the infections caused by adenovirus.

02:54 And we'll start with febrile pharyngitis, which really occurs up to a week or so after the incubation, after the initial inoculation with adenovirus, and then we have onset of acute disease.

03:09 This occurs also for acute respiratory disease and conjunctivitis, and in fact, you'll see this as a pretty typical pattern for the incubation period of all of the adenoviruses.

03:20 Who is at most risk for febrile pharyngitis? Children.

03:24 Very young children, < 3 years of age.

03:27 And that's important because children older than 2 or 3 years of age are the ones who most often get streptococcal pharyngitis, which looks and feels a heck of a lot like febrile pharyngitis with adenovirus.

03:40 So the age here is very important.

03:42 Very young children with a strep throat appearance, more likely than not, have adenovirus.

03:48 Acute respiratory disease, and this is typically an atypical pneumonia, most often occurs in young adults, especially those in close quarters, like military recruits, or inmates in a prison.

04:01 And then conjunctivitis, the so-called pink eye.

04:05 Anybody can get that.

04:06 We list older children and adults, but quite honestly, even younger children in daycare or in preschool, at a playgroup, are going to that municipal swimming pool, anybody can get the conjunctivitis.

04:19 We show here, then, some lovely pictures, and as you see at the bottom on the left side of the slide, febrile pharyngitis, you see a very erythematous throat.

04:29 You can see some slightly enlarged tonsils That appearance looks very much like streptococcal pharyngitis would look.

04:36 However, it's indeed is caused by adenovirus.

04:39 Patients with adenoviral pharyngitis will have the same manifestations as you would expect for strep throat, i.e., fever, a very painful throat, they might have a dry cough because they can't handle those secretions.

04:53 Coryza -- coryza is nasal secretions, which again, they cannot swallow very comfortably.

04:58 The whole appearance is very much like a strep throat.

05:02 For the acute respiratory disease in our military recruits, rapid onset of fever, that dry non- productive cough sore throat is from all the coughing, and also, post nasal drip with rhinorrhea.

05:14 And they may have swollen lymph nodes in the neck, cervical adenitis.

05:19 And then conjunctivitis, the pink eye.

05:21 Well, the picture gives 1000 words.

05:24 And I think we've all seen pink eye.

05:25 We have probably all experienced pink eye.

05:28 So, the entire conjunctiva is inflamed, as you can see in the picture.

05:33 It's sort of itchy, there's excess tearing, sometimes it's a mucus discharge.

05:38 We wake up in the morning with crusted discharge.

05:40 sometimes, we actually have to use a washcloth to open up the eye.

05:44 So, we can see that this is a very classic appearance for pink eye or adenoviral conjunctivitis.

05:51 In adults, unfortunately, this disease potentially could progress to cause a full keratitis, which then might require treatment by an ophthalmologist.

06:03 The next category of infections caused by adenovirus include are atypical pneumonia, gastroenteritis, and appendicitis, and these are, thankfully, a little bit less common than the 3 that we just talked about.

06:15 For atypical pneumonia, here, it's a slightly longer incubation period, up to 2 weeks, versus gastroenteritis, which is anywhere from 3-10 days, the typical incubation we just talked about.

06:27 And similarly, with appendicitis, perhaps a week or so after inoculation with adenovirus.

06:34 The population at risk for atypical pneumonia, everybody: children, adults, you name it.

06:39 For gastroenteritis, it's far more often seen in younger children, the ones who are at risk for other types of viral gastroenteritis.

06:47 And then in appendicitis, similarly, children.

06:50 The reason is that the targeting tissue for the gastrointestinally-focused or tropic adenovirus also can enter the lymphoid tissue to create that latent period, that sort of hiding, within lymphoid tissue.

07:06 And it is exactly that lymphoid swelling which might actually block off the appendix and create the appendicitis.

07:13 So, similar populations for both gastroenteritis and appendicitis.

07:17 The clinical manifestations for atypical pneumonia, exactly what you would expect nonproductive, dry, sharp cough, which persists sometimes for several weeks.

07:28 If one obtains a chest radiograph, or chest X-ray, you'll see bilateral, diffused, patchy inflammation.

07:34 It is an interstitial pneumonia, not an LV or a pneumonia.

07:38 In direct distinction to the classic bacterial lobar pneumonia, this atypical pneumonia without adenovirus involves at least 1 and more often than not, several lobes of lung.

07:50 Far more likely, you'll see it pretty much diffusely throughout the entire lung fields.

07:55 In the gastroenteritis, there are specific serotypes, as we mentioned before, which have tropism for gut tissue and the gut lymphoid tissue.

08:04 As we can see in the slide, serotypes 40, 41, and 42 are very much associated with watery diarrhea and some emesis.

08:15 The serotypes 25, 26, 27 and 28 will cause focused diarrhea, but those are far more often acquired in hospital.

08:21 It's a limited population.

08:24 Any of these, however, because of their growth in the gut associated lymph nodes can cause intussusception, because those swollen lymph nodes serve as a lead point for the intussusception to occur.

08:39 And then finally, as we've been talking about with appendicitis, the same lymphoid hyperplasia compromises blood supply to the appendix and we can get the inflammation.

08:49 Diagnosis of the adenovirus.

08:51 Well, it can -- it does cause dense, basophilic intranuclear inclusion bodies, which you can see identified with the arrows on the slide.

09:01 Identified because everything looks rather dense and basophilic, but these are even darker purple, and you can see them as little clusters within the cytoplasm of their target cells.

09:14 Far more often, since adenovirus can be a pathologic diagnosis by our pathologists, but far more often in clinical practice, we will use serotype specific assays.

09:27 Because adenovirus occurs in so many different serotypes, it's far easier to use immunoassays, a DNA probe, or a PCR -- polymerase chain reaction -- which can target uniform sites for all adenovirus rather than doing antibody-specific testing with a serology panel.

09:46 So, molecular diagnostics are probably the way to go without adenoviral detection, and they pick up the disease far more readily.

09:55 Prevention and treatment.

09:56 Well, this is difficult because adenovirus is a survivor.

10:00 It lives everywhere.

10:02 It's resistant to detergent and acid and drying, and it's resistant to the acid environment in the gut environment.

10:09 This is unfortunate because if you think about your typical kindergarten or preschool, where children's leavings, their mucus, their who-knows-what, gets smeared all over everything, well, those are a highly adenovirus-rich environment, and it's very hard to clean that stuff.

10:28 So, that simply means the best way to prevent adenovirus is wash your hands.

10:34 Not that difficult.

10:36 For those individuals who are at high risk for getting, sort of, an epidemic outbreak of adenovirus and this, again, would be our military recruits, there is a oral vaccine which has decent efficacy, but it is not in common use in the general population.

10:52 Treatment.

10:53 There are no antivirals yet discovered or tested which have any known efficacy against adenovirus, so this is truly a supportive care.

11:02 "Tincture of time," is what we say, trying to make the patient comfortable.

11:06 So, adenovirus is ubiquitous.

11:08 It's all around. It can cause multiple different types of diseases, depending on the tropism of the virus itself.

11:15 But most commonly, it is an unfortunate cause of pink eye, which you can get anywhere and everywhere.