ADENOVIRUS INFECTION

In Immunocompromised Individuals
By Muskan-E Muhemmed
 ADENOVIRUSES
• Adenoviruses are a group of common viruses that can
infect the lining of your eyes, lungs, intestines, nervous
system and urinary tract
• They can cause mild to severe illness, although severe
cases are rare
• Patients with immunosuppression, or co-existing diseases
are at higher risk to develop a severe case of Adenovirus
infection, which will be the primary focus of this report
 TRANSMISSION
• Transmission of adenoviruses in immunocompromised patients occurs in the same way it does from
an infected patient with a normal immune system
• It is spread by the following methods:
- Through respiratory secretions in the air, especially by coughing and sneezing
- Viral shedding in the faeces
- Very close contact/touch, such as shaking hands
- Contact with surfaces exposed to the adenovirus
• Transmission can occur a long time after a patient has recovered from the infection (“viral
shedding”). This is especially common amongst patients that are immunocompromised
• Furthermore, in immunocompromised patients, endogenous reactivation appears to be the
predominant mechanism of infection
 RISK FACTORS
In immunocompromised patients, the main risk factors are:
• Severe lymphopenia; <300CD3+ cells/microlitre peripheral blood
• Allo-hematopoietic stem cell transplantation (HSCT), with in-vivo or ex-vivo depletion of T cells
• Allo-hematopoietic stem cell transplantation with unrelated cord blood graft
• Treatment of cancer patients with alemtuzumab (targeted cancer drug)
 DIAGNOSTICS
• The standard diagnostic method for rapid, quantitative, specific and highly sensitive detection of Human
Adenoviruses, in any diagnostic material, is PCR-based assays
• Hematopoietic stem cell transplantation (HSCT) patients at risk must mandatorily be screened by PCR
• Other immunocompromised patients having unexplained fever, cytopenia, enteritis or elevated liver enzymes
must also undergo PCR screening in peripheral blood to exclude adenovirus infection
• Further screening can be done by analysing other diagnostic specimens of interest
 SYMPTOMS
• As expected, the symptoms of an adenovirus infection in patients with immunosuppression are a lot more severe
than in those who have a normal immune state
• Adenoviruses are capable of causing an extensive range of diseases in patients with immunosuppression, ranging
from:
- Fever, enteritis, elevated liver enzymes, secondary pancytopenia to
- Sever haemorrhagic enteritis, haemorrhagic cystitis, nephritis, pneumonia, encephalitis, myocarditis and
hepatitis
• The most lethal infection is frequently seen in patients with liver diseases
 PREVENTION
• As transmission of adenovirus is the same in regular patients and immunocompromised patients, prevention
methods are the same for both
• Patients shedding the virus should take contact and respiratory droplet precuations
• Simple steps can be followed, such as regular washing hands with soap and water for atleast 20 seconds, avoid
touching nose and mouth with unwashed hands and avoiding close contact with sick persons
• Currently, there is no vaccine against Adenovirus infection for the general public, nor specifically for
immunocompromised patients
• However, there is a vaccine against Adenovirus types 4 and 7, available only for use by US military personnel,
due to being at higher risk. It has not been approved for use outside the military
 TREATMENT
• In regular patients with normal immune statements, there is no specific treatment for adenovirus infection, as it is
usually self limiting
• However, in immunocompromised patients with adenovirus infection, treatment with Cidofovir (anti-viral drug)
has become the latest treatment of choice
• Cidofovir is especially recommended in HSCT patients at risk of infection
• Despite the lack of studies confirming the efficacy, cidofovir is also recommended as preventative therapy in
patients with DNAemia
• Brincidofovir, a prodrug of cidofovir, is currently being studied as an oral and less toxic alternative to cidofovir
 CASES OF IMMUNOCOMPROMISED PATIENTS
WITH ADENOVIRUS INFECTIONS
Case 1
• A 19 year old female was diagnosed with acute lymphoblastic leukaemia
• She was also found to be infected by Adenovirus type 5
• In the post-mortem examination, there was no evidence of residual leukaemia
• Acute yellow atrophy of the liver was visible
• The little amount of remaining intact hepatocytes and degenerating hepatocytes contained nuclear inclusion
bodies
• Crystalline arrays of adenovirus virions were also observed in these cells, by electron microscopy
• There were no nuclear inclusion bodies observed in other tissues
• Patient’s cause of death was due to massive gastrointestinal haemorrhage and hepatic failure caused by the
adenovirus
 CASES OF IMMUNOCOMPROMISED PATIENTS
WITH ADENOVIRUS INFECTIONS
Case 2
• A 56 year old man had been diagnosed with severe pan-lobular emphysema
• Patchy interstitial pneumonia with oedema was seen, along with occasional hyaline membrane formation and
intra-alveolar haemorrhage
• Rare nuclear inclusion bodies were observed
• Patient showed signs of systemic and pulmonary hypertension, also having marked biventricular cardiac
hypertrophy
• Cause of death was a mild adenovirus pneumonia, due to the severe pre-existing emphysema
 CASES OF IMMUNOCOMPROMISED
PATIENTS WITH ADENOVIRUS INFECTIONS
Case 3
• A 20 day old premature infant was diagnosed to have an
extensive pneumonic process with necrosis, sloughed off
bronchiolar epithelium into alveoli and bronchioles, hyaline
membrane formation and a mild mononuclear cell infiltration
(as seen in the image)
• Scattered cells contained amphophilic to basophilic nuclear
inclusion bodies(as seen in the image)
• Cause of death of the infant was due to compromised
pulmonary function, as a result of the adenovirus infection
 CASES OF IMMUNOCOMPROMISED
PATIENTS WITH ADENOVIRUS INFECTIONS
Case 4.
• A 28 year old male patient had widespread Hodgkin’s disease involving
the lymph nodes, spleen and bone marrow
• A few foci of Hodgkin’s disease were also seen in the liver
• Acute yellow atrophy of the liver was observed, and there were 0 viable
hepatocytes
• Amphophilic, basophilic nuclear inclusion bodies were observed in
degenerating hepatocytes (as seen in the image), which also contained
crystalline arrays of adenovirus virions once observed by the electron
microscope
• Similar nuclear inclusion bodies were seen in the proximal renal tubules
and mucosa of the ileum
• There were also presence of Candida abscesses in the lungs,
oesophagus, stomach and colon
• Cause of death was hepatic failure, due to the adenovirus infection
 CASES OF IMMUNOCOMPROMISED
PATIENTS WITH ADENOVIRUS INFECTIONS
• All four clinical illness were associated with high fever, severe systemic complaints such as malaise, lethargy,
fatigue and night sweats
• There was also a similar number of gastrointestinal symptoms complaints
• Pulmonary complaints were also described in all cases, including cough and tachypnoea
• Two out of four cases showed elevation of serum hepatic enzyme levels. Levels were moderate to severe (serum
glutamic pyruvic transaminase >456 W/liter)
• All patients died, with most dying after a rapid downhill course, and others with a prolonged course of disease
• Evidence of adenovirus infection in the patients was demonstrated microscopically by autopsy in the lung, liver
or both
 CONCLUSION
• It must be acknowledged that the same adenovirus was continuously identified from numerous urines in the
patients of the cases mentioned earlier
• Thus, it is logical to further conclude that this is evidence that some types of adenoviruses are either latent or
persistent
• Furthermore, it can be concluded that some adenoviruses can certainly be a cause of serious morbidity and
mortality to patients that have already suppressed immune states
• Thus, an Adenovirus infection should be considered in the etiology of severe or overwhelming illnesses in
immunocompromised hosts
THE END
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