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8/9/2019 Ellis What is Cytomegalovirus
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What is cytomegalovirus (CMV)?
Cytomegalovirus (from the Greekcyto-, "cell", and -megalo-, "large") is a herpes viral
genus of the Herpesviruses group: in humans it is commonly known as HCMV orHuman Herpesvirus 5 (HHV-5). CMV belongs to the Betaherpesvirinae subfamily
ofHerpesviridae, which also includes Roseolovirus. Other herpesviruses fall into thesubfamilies of Alphaherpesvirinae (including HSV 1 and 2 and varicella) or
Gammaherpesvirinae (including Epstein-Barr virus). All herpesviruses share acharacteristic ability to remain latent within the body over long periods.
HCMV infections are frequently associated with salivary glands, though they may befound throughout the body. HCMV infection can also be life threatening for patients
who are immunocompromised (e.g. patients with HIV, organ transplant recipients, or
neonates). Other CMV viruses are found in several mammal species, but speciesisolated from animals differ from HCMV in terms of genomic structure, and have not
been reported to cause human disease.
HCMV is found throughout all geographic locations and socioeconomic groups, and
infects between 50% and 80% of adults in the United States (40% worldwide) asindicated by the presence of antibodies in much of the general population.
Seroprevalence is age-dependent: 58.9% of individuals aged 6 and older are infectedwith CMV while 90.8% of individuals aged 80 and older are positive for HCMV.
HCMV is also the virus most frequently transmitted to a developing fetus. HCMVinfection is more widespread in developing countries and in communities with lower
socioeconomic status and represents the most significant viral cause of birth defects inindustrialized countries. CMV "seems to have a large impact on immune parameters
in later life and may contribute to increased morbidity and eventual mortality."
Virus classification
Group: Group I (dsDNA)
Family: Herpesviridae
Subfamily: Betaherpesvirinae
Genus: Cytomegalovirus
Name Abv. Host
Cercopithecine
herpesvirus 5
(CeHV-5) African green monkey
Cercopithecine
herpesvirus 8
(CeHV-8) Rhesus monkey
Human
herpesvirus 5
(HHV-5) Humans
Pongine
herpesvirus 4
(PoHV-4)
Aotine (AoHV-1) (Tentative species)
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herpesvirus 1
A ti e
herpesvirus 3
(Ao V-3) (T i species)
Pathogenesis
M t healthy people who are i ected by HCM after birth have no symptoms.Someof them develop an infectious mononucleosis/glandular fever-li e syndrome, with
prolonged fever, and a mild hepatitis. A sore throat is common. After infection, the
virus remains latent in the body for the rest ofthe person's life. Overt disease rarelyoccurs unless immunity is suppressed either by drugs, infection or old-age. Initial
HCM infection, which often is asymptomaticis followed by a prolonged, inapparent
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infection during which the virus resides in T - cells without causing detectable damageor clinical illness.
Infectious CMV may be shed in the bodily fluids of any infected person, and can befound in urine, saliva,blood, tears, semen, andbreast milk. The shedding of virus canoccur intermittently, without any detectable signs or symptoms.
Micrograph of CMVplacentitis. One cell on the image (centre) has the characteristic
large nucleus with peri-nuclear clearing. Two cells (centre-left) have the characteristic(cytoplasmic) viral inclusion bodies (small pinkglobules). H&E stain.
CMV infection can be demonstrated microscopically by the detection of intranuclearinclusion bodies. On H&E staining, the inclusion bodies stain dark pink and are called"owl's eye" inclusion bodies.[6]
Cytomegalovirus Retinitis
(See alsoHIV InSite KnowledgeBase chapterCytomegalovirus.)
CMV retinitis is the most common retinal infection in patients with HIV disease, occurring in
15-40% of patients with advanced HIV disease.(20,36-39) It is bilateral in 30-50% of
patients,(40) although that rate may be lower in the setting of treatment, as the disease often
presents unilaterally and the administration of anti-CMV medication almost always prevents
the onset of retinitis in the fellow eye.(36) It is uncommon to find CMV retinitis in HIV-
infected patients with a CD4 count >40 cells/L, and a CD4 count >50-100 cells/L in an
individual with retinitis should prompt a reconsideration of the diagnosis of CMV retinal
infection.
CMV is a DNA virus classified in the herpes group of viruses. Serologic studies indicate a
past CMV infection in approximately 50% of the adult population in urban areas of theUnited States and Europe (41) and close to 100% in the male homosexual population. CMV
disease affecting the eye, however, tends to occur only in developing fetuses and inimmunocompromised patients. CMV infection of the retina leads to viral invasion of retinal
cells with resultant retinal necrosis. Clinically, lesions appear within the retina as multiplegranular white dots with varying amounts of hemorrhage (Figure 2). Although they can be
confused with cotton-wool spots (which may be present in the same eye), CMV lesions differby their tendency to enlarge and coalesce over time. As areas of retinitis enlarge, they appear
to follow the vascular arcades, resulting in an arcuate or triangular zone of infection. Areas of
active infection also may appear to be linear, seemingly following the retinal vessels or nerve
fiber layer into the periphery. Frosted branch angiitis may be seen in conjunction with CMV
retinitis (Figure 3). After several weeks, atrophic tissue that has lost the capacity to support
viral replication replaces actively infected regions of retinal tissue.(42,43) The underlying
retinal pigment epithelium demonstrates pigment loss and migration, resulting in increased
visualization of the underlying choroidal vasculature.
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Other findings associated with CMV retinitis include perivasculitis, vascular attenuation, andvessel closure,(20,44) as well as vitritis, anterior uveitis, and papillitis.(45-47)
Although CMV retinitis usually responds to initial therapy, the prompt recognition of
recurrent CMV retinitis is of particular importance. The presentation of recurrence may be so
subtle that active disease may remain undetected for extended periods of time. Early
recurrences appear as subtle white or gray zones of retinitis with little, if any, accompanyingretinal hemorrhage. Recurrence usually begins at the margins of previously active infection
and tends to "smolder" rather than actively progress. Nevertheless, it will continue to spread,
slowly but inexorably, if the treatment regimen is not altered. The reintroduction of induction
doses of medication for a period of 2-3 weeks often will inhibit progression of these recurrent
lesions. Retinitis progression may recur, however, eventually necessitating alternative
treatments. Patients with recurrent infection that is quite "active" in appearance and
accompanied by the presence of significant retinal whitening and hemorrhage while they are
on appropriate levels of maintenance therapy have an especially poor prognosis for
preservation of sight, even with the use of increased doses of medication.
With the introduction of effective ART, the incidence of CMV retinitis has been noted to
decrease by about 75%.(48) However, the incidence of OI, especially new or recurrent CMVretinitis, remains high during the first few months of ART, consistent with the delay in
immune recovery following initiation of ART.(49) Prior to the availability of effective ART,the median time to progression of treated CMV was 3-9 months, and the lack of CMV
progression in patients on ART is most likely due to improved CMV-specific immunity.(50)In patients with a history of CMV disease who subsequently receive ART, immune
reconstitution may result in inflammatory retinal lesions, vitritis, or uveitis. (See chapterImmune Reconstitution.)
Systemic Anti-CMV Therapy
For oral and intravenous treatment of CMV infection, seeHIV InSite KnowledgeBase
chapterCytomegalovirus.
Clinical Manifestations
Chorioretinitis
Chorioretinitis most commonly occurs in patients with CD4 lymphocyte counts
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may occur at either the periphery or center of the fundus. If left untreated, lesions generallyprogress within 2 to 3 weeks and can result in blindness. Retinitis often begins unilaterally,
but progression to bilateral disease is common. Systemic CMV disease involving otherviscera may also be present.
CMV retinitis accounts for at least 90% of HIV-related infectious retinopathies.(13)
Differentiating suspected CMV retinitis from cotton wool spots is essential. Cotton woolspots appear as small, fluffy white lesions with indistinct margins and are not associated with
exudates or hemorrhages. These lesions do not progress and often undergo spontaneous
regression. Toxoplasmosis is the second most common opportunistic infection of the eye, but
it is not associated with hemorrhage and typically occurs in patients with cerebral
toxoplasmosis. Syphilis, herpes simplex virus, varicella-zoster virus, and tuberculosis are
other infections that may rarely involve the retina.
Patients with confirmed CMV chorioretinitis should begin treatment promptly. A variety of
systemically administered agents as well as local, intravitreal therapies have demonstrated
efficacy in delaying time to progression of retinitis. The choice of initial treatment should be
based on several factors, including the patient's antiretroviral history (treatment naive vs
failing therapy) and clinical status (especially underlying myelosuppression or renalimpairment), location of lesion (sight threatening or not), concomitant medication (with
potentially overlapping toxicity), and patient preference (especially regarding placement ofan indwelling intravenous catheter). Before the availability of ART, CMV retinitis regularly
progressed once therapy was discontinued, so maintenance treatment was considerednecessary; and even with maintenance therapy, reactivation of retinitis and/or development of
new lesions would commonly occur. However, if ART is successful in restoring CD4 countsto at least 100 cells/L (although to 150-200 cells/L is better), it is possible to stop
maintenance therapy. This should not be attempted until a patient's CD4 count has remained
above the levels mentioned for at least 3 months because the lymphocyte response requires
time to reach full effectiveness. If maintenance therapy is discontinued, patients should be
followed carefully for clinical or laboratory evidence of drug failure. Other factors to
consider when deciding to discontinue maintenance therapy include patient adherence to
ART medications, location of the retinal lesion, and the patient's vision in the unaffected eye.
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Cmv of retina
How could I have gotten CMV?Most people are exposed to CMV at birth or as children. The virus remains dormant in
their bodies for their lifetime
Cytomegalovirus is often transmitted through infected bodily fluids (urine, saliva,breast milk) that come in contact with the hands of a susceptible person.
From the hands, CMV is then absorbed when the person touches his or her nose ormouth.
CMV is also transmitted through transplanted organs, stem cell transplants, and rarely,through blood transfusions. This is why your doctor will carefully check your blood
for active CMV.
How will I be tested for this virus?
A blood sample will be taken by a nurse or phlebotomist once a week, or if you showsypmtoms of CMV infection. These samples will be taken for at least the first 100
days after your stem cell transplant.The sample must be drawn before 9 a.m. Results are either negative or positive.
If my blood tests negative, will I still need to be retested?Yes. It is important to test frequently for CMV while your immune system is sup-
pressed from the transplant and
immunosuppressive medication. You are at risk for having active CMV while your
immune system is suppressed.
If my blood tests positive for active CMV, what can I expect?
A CMV positive test will give a number, which tells the amount of virus found in yourblood. The number (amount of virus), will help your doctor decide if you should take
an antiviral medication to kill the virus.If your doctor decides not to put you on antiviral medication, he or she will recheck a
blood sample in a few days.
If your doctor decides to put you on an antiviral medication, you will receive thismedication every day until your blood test for CMV comes back with a lower number
than the previous test or is negative.Depending on your transplant and blood test results, your medication will be either in
tablet or in I.V. (intravenous) form. If you need I.V. medication, you may need to beadmitted to the hospital for 1 to 2 weeks.
Will my donor be tested, too?Yes. If your donor is positive for CMV, he or she can transmit this infection to you
through the donated stem cells. Knowing if your donor is a CMV carrier helps yourdoctor to predict your risk for active CMV infection.
If I have not been exposed to CMV before my transplant, how can I protect
myself from future exposure?
Simple hand washing with soap and water removes the virus from the hands. Werecommend frequent hand washing.
If you have other questions about CMV, please feel free to ask your doctor or nurse.
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Transmission and prevention
Transmission of HCMV occurs from person to person through bodily fluids. Infection
requires close, intimate contact with a person excreting the virus in their saliva, urine,or other bodily fluids. CMV can be sexually transmitted and can also be transmittedviabreast milk, transplanted organs, and rarely fromblood transfusions.
Although HCMV is not highly contagious, it has been shown to spread in householdsand among young children in day care centers.[1] Transmission of the virus is often
preventable because it is most often transmitted through infected bodily fluids that
come in contact with hands and then are absorbed through the nose or mouth of asusceptible person. Therefore, care should be taken when handling children and items
like diapers. Simple hand washing with soap and water is effective in removing thevirus from the hands.
HCMV infection without symptoms is common in infants and young children; as a
result, it is common not to exclude a child known to be infected from school or
another institution. Similarly, hospitalized patients are not typically separated orisolated.
[edit] Vaccine
Main article: Cytomegalovirus vaccine
Cytomegalovirus vaccines are still in the research and development stage.
Aphase 2 study of a CMV-vaccine published in 2009 indicated an efficacy of 50%, -
thus the protection provided was limited and a number of subjects contracted CMV
infection despite the vaccination. In one case also congenital CMV wasencountered. [9]
[edit] CMV diseases
CMV infections are most significant in the perinatal period and in
immunocompromised patients.
[edit] Pregnancy and congenital infection
Main article: Congenital cytomegalovirus infection
HCMV is one of the TORCH infections that lead to congenital abnormalities. Theseare: toxoplasmosis, rubella, herpes simplex, and cytomegalovirus. Congenital HCMVinfection occurs when the mother suffers a primary infection (or reactivation) during
pregnancy.
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[edit] Immunocompromised adults
Primary CMV infection in patients with weakened immune systems can lead toserious disease. However, a more common problem is reactivation of the latent virus.
Infection with CMV is a major cause of disease and death in immunocompromised patients, including organ transplant recipients, patients undergoing hemodialysis,patients with cancer, patients receiving immunosuppressive drugs, and HIV-infected
patients. Exposing immunosuppressed patients to outside sources of CMV should beminimized to avoid the risk of serious infection. Whenever possible, patients withoutCMV infection should be given organs and/or blood products that are free of the virus.
In patients with a depressed immune system, CMV-related disease may be much moreaggressive.
Specific disease entities recognised in those people are
y CMV hepatitis, which may cause fulminant liver failurey cytomegalovirus retinitis (inflammation of the retina, characterised by a "pizza
pie appearance" on ophthalmoscopy)y cytomegalovirus colitis (inflammation of the large bowel)y CMV pneumonitisy CMV esophagitis[10]y polyradiculopathy, transverse myelitis, and subacute encephalitis
Patients without CMV infection who are given organ transplants from CMV-infected
donors should be given prophylactic treatment with valganciclovir (ideally) or
ganciclovir and require regular serological monitoring to detect a rising CMV titre,which should be treated early to prevent a potentially life-threatening infection
becoming established.
[edit] Immunocompetent adults
CMV infections can still be of clinical significance in adult immunocompetent
populations:
y CMV mononucleosis (some sources reserve "mononucleosis" for EBV only)y
Post-transfusion CMV - similar to CMV mononucleosisy A 2009 study suggests that CMV infection may be linked to the development
ofarterial hypertension.[8] Mice fed a high cholesterol diet showed significantly
more vascular damage and hypertension when they had been infected withCMV. CMV infection stimulated cytokines IL6, TNF, and MCP1 in theinfected mice indicating that the infection led to an inflammatory response in
vessels and other tissues. Further, renin and angiotensin II release were
increased in these animals as additional factors to lead to hypertension. Inhumans CMV infection has been demonstrated in the aortic smooth muscle
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cells from patients with abdominal aortic aneurysms suggesting that CMVinfection contributes to vascular disease.
[11][12]
Diagnosis
Most infections with CMV are not diagnosed because the virus usually produces few,if any, symptoms and tends to reactivate intermittently without symptoms. However,
persons who have been infected with CMV develop antibodies to the virus, and theseantibodies persist in the body for the lifetime of that individual. A number oflaboratory tests that detect these antibodies to CMV have been developed to determine
if infection has occurred and are widely available from commercial laboratories. In
addition, the virus can be cultured from specimens obtained from urine, throat swabs, bronchial lavages and tissue samples to detect active infection. Both qualitative andquantitative polymerase chain reaction (PCR) testing for CMV are available as well,
allowing physicians to monitor the viral load of CMV-infected patients.
CMV pp65 antigenemia test is a immunofluorescence based assay which utilizes an
indirect immunofluorescence technique for identifying the pp65 protein of
cytomegalovirus in peripheral blood leukocytes. The CMV pp65 assay is widely usedfor monitoring CMV infections and its response to antiviral treatment in patients whoare under immunosuppressive therapy and have had renal transplantation surgery as
the antigenemia results are obtained about 5 days before the onset of symptomaticCMV disease. The advantage of this assay is the rapidity in providing results in a fewhours and that the pp65 antigen determination represents a useful parameter for the
physician to initiate antiviral therapy. The major disadvantage of the pp65 assay is that
only limited number of samples can be processed per test batch.
CMV should be suspected if a patient has symptoms of infectious mononucleosis but
has negative test results for mononucleosis and Epstein-Barr virus, or if they showsigns of hepatitis, but has negative test results forhepatitis A, B, and C.
For best diagnostic results, laboratory tests for CMV antibody should be performed byusing paired serum samples. One blood sample should be taken upon suspicion ofCMV, and another one taken within 2 weeks. A virus culture can be performed at any
time the patient is symptomatic. Laboratory testing for antibody to CMV can be
performed to determine if a woman has already had CMV infection. However, routinetesting of all pregnant women is costly and the need for testing should therefore beevaluated on a case-by-case basis.
[edit] Serologic testing
The enzyme-linked immunosorbent assay (orELISA) is the most commonly availableserologic test for measuring antibody to CMV. The result can be used to determine if
acute infection, prior infection, or passively acquired maternal antibody in an infant is
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present. Other tests include various fluorescence assays, indirect hemagglutination,(PCR) and latex agglutination.
An ELISA technique for CMV-specific IgM is available, but may give false-positiveresults unless steps are taken to remove rheumatoid factoror most of the IgGantibody
before the serum sample is tested. Because CMV-specific IgM may be produced in
low levels in reactivated CMV infection, its presence is not always indicative of
primary infection. Only virus recovered from a target organ, such as the lung, providesunequivocal evidence that the current illness is caused by acquired CMV infection. If
serologic tests detect a positive or high titer of IgG, this result should notautomatically be interpreted to mean that active CMV infection is present. However, if
antibody tests of paired serum samples show a fourfold rise in IgG antibody and asignificant level of IgM antibody, meaning equal to at least 30% of the IgG value, or
virus is cultured from a urine or throat specimen, the findings indicate that an activeCMV infection is present.
[edit] Relevance to blood donors
Although the risks discussed above are generally low, CMV assays are part of the
standard screening for non-directed blood donation (donations not specified for a particular patient) in the U.S. CMV-negative donations are then earmarked fortransfusion to infants or immunocompromised patients. Some blood donation centers
maintain lists of donors whose blood is CMV negative due to special demands. [13]
[edit] Treatment
Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV) is an
immunoglobulin G (IgG) containing a standardized amount of antibody t oCytomegalovirus (CMV). It may be used for the prophylaxis of cytomegalovirusdisease associated with transplantation of kidney, lung, liver, pancreas, and heart.
Alone or in combination with an antiviral agent, it has been shown to:
y Reduce the risk of CMV-related disease and death in some of the highest-risktransplant patients
y Provide a measurable long-term survival benefity Produce minimal treatment-related side effects and adverse events.[14]
Ganciclovir (Cytovene) treatment is used for patients with depressed immunity whohave either sight-related or life-threatening illnesses. Valganciclovir (Valcyte) is anantiviral drug that is also effective and is given orally. The therapeutic effectiveness is
frequently compromised by the emergence of drug-resistant virus isolates. A variety
of amino acid changes in the UL97 protein kinase and the viral DNA polymerase have been reported to cause drug resistance. Foscarnet or cidofovir are only given topatients with CMV resistant to ganciclovir, because foscarnet has bad nephrotoxicity,
resulting in increased or decreased Ca2+ or P, and decreased Mg2+.
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[edit] Genomics
This section does not cite any references or sources.
Please help improve this article by adding citations to reliable sources.
Unsourced material may be challenged and removed. (December 2009)
As a result of efforts to create an attenuated-virus vaccine, there currently exist two
general classes ofCM .
y Cli ical i lates comprise those viruses obtained from patients and representthe wild-type viral genome.
y Laboratory strai s have been cultured extensively in the lab setting andtypically contain numerous accumulated mutations. Most notably, thelaboratory strain AD169 appears to lack a 15kb region ofthe 200kb genome
thatis presentin clinicalisolates. This region contains 19open reading frames
whose functions have yet to be elucidated. AD169 is also uni ue in that it isunable to enterlatency and nearly always assumes lytic growth upon infection.
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INTRODUCTIONCytomegalovirus is the most common cause of intrauterine
infection, occurring in 0.2% to 2.2% of all live births, and is
a common cause of sensorineural hearing loss and mentalretardation.1,2Most healthy people who acquire CMV after birth experience
few or no symptoms and no long-term sequelae. Some
experience a mononucleosis-like syndrome with symptomsincluding malaise, persistent fever, myalgia, cervical
lymphadenopathy, and, less commonly, pneumonia andhepatitis.3 After the primary infection, defined as CMV
infection in a previously seronegative person, the virusbecomes dormant and exists in a latent state, from which it
can be reactivated. This is designated as recurrent (secondary)infection.4 In addition, there seem to be several strains of
CMV that infect humans, so reinfection can occur, even in
immunocompetent individuals. Therefore, secondaryinfection, defined as intermittent excretion of the virus in
the presence of host immunity, may be due to either reactivationof an endogenous virus or exposure to a new virus
strain from an exogenous source. Differentiation betweenthese two kinds of secondary infection is not possible by
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serology but only by molecular analysis of virus isolates.35Seroconversion occurs in 1% to 4% of all pregnancies and
is higher in women who are of low socioeconomic status orwho have poor personal hygiene.6,7
Congenital infections are the result of transplacentaltransmission of CMV. Transmission to the fetus may occur
because of primary or secondary maternal infection.
CMV retinitis is a recognized complication of immunosuppressive
therapy, and may cause profound bilateral visual
loss. Treatment involves reduction of levels of immunosuppressionwhere possible and administration of ganciclovir,which may need to be continued as maintenance therapy once
retinitis has become quiescent and until immunocompetence
is restored.Retinal neovascularization develops in response to retinalischaemia or intraocular inflammation. Although this
patient had inflammatory eye disease, the clinical courseindicates that the stimulus to neovascularization was retinalischaemia secondary to retinal vascular occlusions. Retinal
vascular changes are very rarely seen in Wegener's
granulomatosis5, except in its necrotizing sarcoidal type6,which was not present in this patient. Also there was noevidence of diabetes mellitus, systemic hypertension, or
carotid artery disease to explain the retinal vascular disease.CMV retinitis is frequently accompanied by retinal vascularchanges, and infection of endothelial cells by CMV has been
demonstrated histologically in CMV retinitis in non-AIDSpatients7'8. It is suggested that the retinal vascular changesin this patient were due to the CMV infection and they wereresponsible for the widespread retinal ischaemia leading to
gross retinal neovascularization, vitreous haemorrhages, and
traction retinal detachment; a course of events that has notpreviously been described in CMV retinitis.
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AIDS and Cytomegalovirus (CMV) Retinitis
T4 Cell Count
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the same eye before (left) and after treatment (right). The classical appearance ofCMV retinitis is that of a haemorrhagic retinal necrosis - sometimes described as
ketchup (tomato sauce) on cottage cheese at the posterior pole with extension of thelesions along the vascular arcade and sheathing of the vessels. The white edge at the
border of the lesion represents the active infection which will progress at a rate ofabout one disc diameter per week if untreated. The necrotic area left behind the
advancing white border shows a thinned and irregularly pigmented atrophic retina.Infection of the perifoveal or peripapillary (around the optic nerve) area is associated
27
with early visual loss. Sometimes small islands of CMV infection are seen near to theadvancing border of a more massive lesion. The peripheral lesions may have a moregranular appearance with less haemorrhages (dry, granular form of CMV). The
disease
is bilateral in about 50% of patients. Once established, CMV retinitis is relentlesslyprogressive and the whole retina is destroyed within six months if no treatment is
provided. Retinal detachment is a late complication of CMV retinitis and is estimated
to occur in about 20 to 30% of eyes with CMV infection.Two drugs which are available for the treatment of CMV retinitis are ganciclovir and
foscarnet. Both drugs are virostatic which means that they should be continuedindefinitely in AIDS patients. The profile of toxicity is different: ganciclovir
suppressesthe bone marrow causing neutropenia while foscarnet is nephrotoxic. Foscarnet hasanti-HIV properties which would explain the prolongation of life seen in AIDS
patients
treated with this compound as opposed to ganciclovir. Unfortunately, the morecommon side effects of foscarnet make ganciclovir a more convenient drug for most
patients. It should be emphasised that these drugs are very expensive and that their
administration pre-supposes careful monitoring of renal function (foscarnet) and
neutrophil counts (ganciclovir). These two factors mean that they cannot be usedroutinely in most developing countries. (An alternative drug to ganciclovir andfoscarnet is cidofavir which does have the advantage of once weekly treatment).
Drug Induction Maintenance
Ganciclovir 5 mg/kg IV twice daily for 2 to 3 weeks 5 mg/kg IV once every day or6 mg/kg IV once daily for five
days a week
Foscarnet 60 mg/kg IV three times daily for 2 to3 weeks90 to 120 mg/kg IV once daily
After initiation of treatment there is usually a 2 to 3 week period before there is
clinical evidence of regression of the lesions. Oral ganciclovir may be given once thedisease is 'controlled'. Even on maintenance therapy, however, nearly all patients will
show evidence of reactivation of CMV retinitis with a median time of reactivation of 3months.
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Differential Diagnosis of CMV Retinitis
(1) Cotton-Wool Spots
Differential Diagnosis of CMV Retinitis / Toxoplasmosis
Which eye diseases should be considered in the differential diagnosis of CMV
retinitis?
Three other eye diseases may have clinical similarities to CMV retinitis.
1. Cotton-wool spots (See top image above)2. Retinitis due to toxoplasmosis (See slide 17)3. Acute retinal necrosis (See slide 18)
Cotton-wool spots, especially when accompanied by small haemorrhages, maysimulate incipient CMV retinitis.The photographs show cotton-wool spots above and an example of CMV retinitis
below.Cotton-wool spots are located in the nerve fibre layer, the most superficial layer of the
retina. CMV lesions are located more deeply and have a more granular aspect.
Confluent cotton-wool spots may be particularly difficult to distinguish from CMVlesions. Observation over a 2 week period will give the answer as CMV lesions will
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progress, in contrast to cotton-wool spots which remain stationary or even regress
What are the clinical features of the second eye disease that may simulate
CMV retinitis?
Toxoplasmic retinitis in AIDS patients is less common than CMV retinitis and
accounts probably for only 1 to 3% of retinal infections. The two infections can beconfused in AIDS patients because of similar clinical features. The exact diagnosis iscritical, if one intends to treat the patient, because toxoplasmosis requires different
medical treatment (sulfadiazine, pyrimethamine) to CMV retinitis. The photographsshow retinitis of toxoplasmosis above and an example of CMV retinitis below.The following factors may be helpful in the differential diagnosis:
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Differential Diagnosis of CMV Retinitis / PORN
The photographs show PORN (above) andCMV retinitis (below).
Acute retinal necrosis (ARN) is a necrotising herpetic retinopathy due to herpeszoster (or herpes simplex). It is the second most common infection of the eye in AIDS
patients, although it is still relatively uncommon in comparison to CMV retinitis.Two different clinical forms of acute retinal necrosis due to herpes zoster are
described in HIV-infected patients: the so-called classical ARN syndrome, which has
also been described in immunocompetent hosts, and the atypical ARN syndrome,which seems to be more common in HIV-infected patients.Classical ARN is characterised by confluent necrotic lesions in the peripheral fundus,
marked vitreous and anterior chamber inflammation, and occlusive vasculitis andhaemorrhages. The lesions in atypical ARN are characterised by homogeneous,creamy-yellow opacification of the deep retina. Numerous lesions are scattered bothin
the periphery and at the posterior pole. There is little or no vitreous or anteriorchamber inflammation. The areas along the big vessels seem to be spared. Atypical
ARN seems to involve primarily the outer retinal layers and has been namedprogressive outer retinal necrosis (PORN).
Both ARN and PORN are rapidly progressive and will lead to blindness throughretinalnecrosis or retinal detachment in the course of some weeks. Patients with ARN will
have both pain and visual symptoms, whereas patients with PORN do not experience
pain but complain of visual loss or constriction of their visual fields. Both clinicalsyndromes are two different presentations of necrotising varicella-zoster retinitis. Theseverity of a patient's immune dysfunction probably determines whether the same
virus causes ARN (better immunity) orPORN (worse immunity).The differential diagnosis between PORN andCMV retinitis in AIDS patients isimportant.
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References
1.^ a b c d e f Ryan KJ, Ray CG (editors) (2004). Sherris MedicalMicrobiology (4th ed.). McGraw Hill. pp. 556; 5669.
ISBN0838585299.
2.^ Offermanns S, Rosenthal W (2008).Encyclopedia of MolecularPharmacology (2nd ed.). Springer. pp. 437438. ISBN978-3-
540-38916-3.
3.^ Staras SA, Dollard SC, Radford KW, Flanders WD, Pass RF,Cannon MJ (November 2006). "Seroprevalence of
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