ellis what is cytomegalovirus

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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