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Abstract

Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent patients are not well documented. From December 1998 through June 2001, serum samples obtained from 7630 patients in Cambridge and Chelmsford, United Kingdom, were tested for CMV immunoglobulin M. CMV immunoglobulin G avidity was used to confirm CMV infection. A total of 124 patients (106 patients treated by general practitioners [GPs] and 18 hospitalized patients) with CMV infection were identified. The most frequent symptoms were malaise (67%), fever (46%), and sweats (46%), and the most frequent finding was abnormal liver function test results (69%). Twelve percent of patients had a relapsing illness, and many had symptoms that lasted for up to 32 weeks (mean duration of symptoms, 7.8 weeks). GPs reported that there was a significant benefit in making the diagnosis of CMV infection; it provided reassurance and avoided the need for further investigations. We have identified symptoms associated with CMV infection in immunocompetent patients who present to GPs or who are admitted to the hospital.

Cytomegalovirus (CMV) is a member of the Herpesviridae family. Infection is often acquired early in life and is usually asymptomatic [ 1]. CMV is also transmitted by sexual contact and is associated with congenital damage when the mother has infection at any stage in pregnancy [ 2, 3].

CMV infection is frequently reported in immunocompromised patients. In transplant recipients [ 4-6] and HIV-positive patients [ 7-9], CMV infection is associated with severe, life-threatening infection. There are only a few reports describing symptoms in immunocompetent patients [ 10-15]. Most studies have involved patients with hepatitis, but there are reports of patients with neurological and intestinal symptoms [ 14-18]. We have previously described a prolonged and relapsing illness involving fever, sweats, and malaise in grandmothers who acquired infection from their grandchildren [ 19]. Following up this work, we conducted a study in which we sought evidence of CMV infection in immunocompetent patients in the community and in hospitals in Cambridge and Chelmsford, United Kingdom, during 1998-2001. We describe the symptoms, report the duration of symptoms, and demonstrate the value of diagnosis of CMV infection in immunocompetent patients.

Methods

Patients. Immunocompetent patients with evidence of recent CMV infection (CMV IgM level, >300 U/mL) were selected for the study. Patients with hematological and/or oncological disorders, those who had received transplants, and those receiving immunosuppressive therapy (excluding low-dose steroid therapy) were excluded from the study. The study group comprised 124 (1.63%) of 7630 patients whose serum samples were tested during the period of December 1998 through June 2001 in the Cambridge and Chelmsford Public Health Laboratories. Patients' serum samples were selected for CMV IgM testing if they presented with pyrexia, malaise, lymphadenopathy, jaundice, hepatitis, sweats, or a glandular fever-like illness.

CMV IgM detection. CMV infection was diagnosed by the detection of CMV-specific IgM in serum samples (Eurogenetics CMV IgM ELISA assay). Patients were only included in the study if they had CMV-specific IgM levels of >300 U/mL in the absence of Epstein-Barr virus, hepatitis A, antibody to hepatitis B core antigen, and Toxoplasma gondii IgM antibodies and of rheumatoid factor.

CMV IgG avidity. The specificity of our CMV IgM assay was verified by performing CMV IgG avidity tests on all available samples from the study by using a modified CMV IgG EIA (Biokit) and 8M urea.

Clinical data. Four to 12 months after CMV infection was diagnosed, a questionnaire was sent to the patient's general practitioner (GP) to document the symptoms, duration of symptoms, and clinical value of diagnosis. GPs were also asked whether the patient had been receiving immunosuppressive drugs or had a malignant disease. If the questionnaires were not returned, GPs were telephoned for the information. Medical records of hospitalized patients were scrutinized to gain similar information.

Results

During the study period (December 1998 through June 2001), 124 patients (106 of whom presented to their GPs and 18 of whom were hospitalized) with CMV infection (CMV IgM level, >300 U/mL) were detected. The ratio of male to female patients was 1.2 : 1. The age range was 16-86 years (table 1). CMV IgG avidity was used to confirm acute CMV infection.

In patients for whom a recent date of symptom onset (<2 weeks) was known, CMV IgM was always detectable. However, in most of these patients, CMV IgG was not detected at the time of study (i.e., <2 weeks after symptom onset). Additional serum samples were sought from these patients, and CMV IgG appeared 2-3 weeks after the onset of symptoms. In patients for whom serial serum samples were available, IgM was detectable for 4-6 months after the onset of symptoms.

The age distribution of patients with CMV infection is shown in figure 1. Infection was most frequently found in patients aged 20-59 years (90% of all patients). The most typical clusters of symptoms associated with CMV infection in these immunocompetent patients are shown in table 1 and include abnormal liver function test (LFT) findings, malaise, jaundice, sweats, and pyrexia. In total, 32% of patients had this combination of symptoms.

Patients for whom LFTs were performed had the following laboratory values: mean alanine aminotransferase level, 121 U/L (range, 23-1151 U/L); mean alkaline phosphatase level, 162 U/L (range, 44-1342 U/L); and mean bilirubin level, 22 μmol/L (range, 6-349 μmol/L). Among patients for whom the temperature was measured, the mean temperature was 38.3°C (range, 37.2°C-40.0°C). Among those patients who had sweats, 60% had at sweats at night, 24% had them during the day, and 16% had them during both day and night. Among those patients who had lymphadenopathy, 88% and 16% had cervical and inguinal glands, respectively.

Symptoms in community and hospitalized patients were broadly similar (table 1). However, hospitalized patients had a higher incidence of abnormal LFT findings, malaise, sweats, pyrexia, respiratory symptoms, confusion, and abdominal pain but a lower incidence of lymphadenopathy.

Fifteen patients (12%) had a relapsing illness (with clinical improvement followed by recurrent symptoms) ( table 1). The duration of symptoms was 1-32 weeks (mean duration, 7.8 weeks). The initial diagnoses made by GPs for 68 of these patients are shown in table 2.

The response rate of GPs to questionnaires was 82%. All GPs were asked whether their patients with CMV infection had a malignancy or were receiving immunosuppressive drugs around the time of diagnosis of CMV infection. Eighty-seven of 91 patients for whom information was received had not been given immunosuppressive drugs, nor was a malignant disease diagnosed within 4-12 months of the CMV infection. The other 4 patients had received steroid treatment 2-4 months before the onset of CMV infection.

Four patients were pregnant at the time of CMV infection. Three delivered apparently healthy children, but 1 child had interuterine growth retardation and was born with severe hearing impairment.

There was significant benefit in making a diagnosis of CMV infection in these patients. For 35 patients (33%) seen by GPs, there was relief that the prolonged illness was not serious and would eventually resolve with no sequelae. For 6 patients (6%) seen by GPs, diagnosis of CMV infection avoided further investigations. Two patients were scheduled to have liver biopsies when CMV infection was diagnosed.

Discussion

Severe CMV disease is usually associated with infection in immunocompromised patients [ 4-9]. There are few reports of severe or prolonged symptomatic infection in immunocompetent patients [ 10-18]. Most of these studies have reported hepatitis [ 10, 11, 14] and colitis [ 16-18] in association with CMV infection. In the largest study, Faucher et al. [ 14] performed a retrospective analysis of 116 hospitalized patients and outpatients. Fever was noted in 99% of patients, with a mean duration of 21 days. Fifty-one percent of patients had headache, 46% had myalgia, and 36% had splenomegaly. Respiratory and neurological symptoms were noted in 8% and 1% of patients, respectively.

In 1995, we reported a study of older patients who had acquired CMV infection from their congenitally infected newborn grandchildren and who had malaise [19]. We described this as the "feverish granny syndrome," and that study heightened our interest in the diagnosis of CMV infection in immunocompetent patients. In 1998, we reviewed the criteria that we used for selecting serum samples to be tested for CMV IgM and expanded the range of symptoms to include malaise, fever, hepatitis, elevated LFT values, lymphadenopathy, glandular fever-like illness, sore throat, and sweats. In the subsequent 3 months, we observed an increase in the number of patients with CMV infection who had presented to their GPs. We had issued an interim analysis of the results in our Cambridge GP newsletter, presented our findings at 3 GP meetings, and asked them to take part in our study of CMV infection in immunocompetent patients. Several GPs began referring samples in which they suspected-with a good degree of accuracy-CMV infection. We also extended our study to GPs referring samples to Chelmsford Public Health Laboratory and sought evidence of CMV infection in hospitalized immunocompetent patients in Cambridge and Chelmsford.

CMV infection was diagnosed by detecting CMV-specific IgM in the absence of other diagnoses of viral and T. gondii infections. This test can have nonspecific results associated with lower CMV IgM levels. Therefore, we only considered patients with CMV IgM levels of >300 U/mL as having evidence of recent CMV infection. Most patients had much higher amounts of CMV IgM (up to 1000 U/mL). Serum samples obtained from these patients were also positive for low-avidity CMV IgG. Although no reference standard test for the diagnosis of primary CMV infection exists, determination of CMV IgG avidity has been used in several studies to distinguish accurately between recent and past CMV infection [ 20-22].

Eighty-five percent of the patients in our study with symptomatic CMV infection presented to their GPs, and 15% of patients were hospitalized inpatients. It cannot be assumed that 15% of all immunocompetent patients with CMV infection will be hospitalized, because many patients with milder illness will not present to their GPs or have samples sent to the laboratory. As can be seen in table 1, hospitalized patients had more-severe symptoms. Patients who presented to GPs were an unselected group that represented the local community. Many patients had prolonged and/or relapsing symptoms, and few GPs had suspected CMV infection in their initial diagnosis until later in the study period, when they had become more familiar with the typical presenting symptoms (i.e., pyrexia, malaise, and hepatitis/abnormal LFT findings).

Antiviral drugs, such as ganciclovir, are available for treating CMV infection, but they are licensed for use only in severe or life-threatening illness in immunocompromised patients. Despite the nonavailability of antiviral treatment for immunocompetent patients, GPs reported that diagnosing CMV infection had benefits. In particular, although symptoms may be prolonged (up to 32 weeks; table 1), all patients could be reassured that symptoms would eventually resolve and that there would be no sequelae. They also gained reassurance that additional investigations were not required.

None of our patients with CMV infection had malignancies; however, because symptomatic CMV infection can be more prevalent among these patients, malignancies must always be considered a possibility. Four of our patients were receiving steroid treatment (prednisolone, 3-20 mg q.d., for 2-4 months before onset of symptoms), which increases the incidence of symptomatic CMV infection. We believe that, by recognizing the range of symptoms associated with CMV infection in immunocompetent patients and by diagnosing infection more frequently, there is significant benefit for patients and doctors.

Acknowledgments

We are grateful to the general practitioners and physicians in Cambridge and Chelmsford, United Kingdom, who collaborated in this study and the laboratory staff who performed the diagnostic assays.

References

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Cytomegalovirus Infection in Immunocompetent Patients | Clinical Infectious Diseases | Oxford Academic

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Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent patients are not well documented. From December 1998 through June 2001, serum samples obtained from 7630 patients in Cambridge and Chelmsford, United Kingdom, were tested for CMV immunoglobulin M. CMV immunoglobulin G avidity was used to confirm CMV infection.

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* Cytomegalovirus (CMV) testing is used to determine whether someone with signs and symptoms has an active CMV infection. *Sometimes it may be ordered to help determine whether someone had a prior CMV infection.
* The choice of tests and samples collected depends on the age of the person, their general health status and symptoms, and on the health practitioner's clinical findings and suspicions of organ involvement.
* antibody testing is done on blood sample - two antibodies; IgM & IgG
*antibody testing also used to determine immunity to primary CMV infections.

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CMV Tests: The Test | Cytomegalovirus Tests

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Describes how the CMV (cytomegalovirus) test is used, when a CMV test is ordered, and what the results of a CMV test might mean

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The enzyme-linked immunosorbent assay (ELISA) is the most common serologic test for measuring antibody to CMV.

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Cytomegalovirus (CMV) infection facts

CMV is a common virus in the same family as herpesvirus, and it can infect anyone.

CMV is spread by direct contact of body fluids, such as saliva, blood, urine, semen, vaginal fluids, and breast milk. Thus breastfeeding, blood transfusions, organ transplants, and sexual contact are possible modes of transmission.

Most healthy people do not experience any symptoms when infected with CMV, and it does not pose a serious health concern. A majority of adults have antibodies consistent with past infection.

Most healthy children and adults who do have symptoms will recover from CMV infection without complications and do not require antiviral treatment.

However, in those with a weakened immune system, CMV can cause serious disease (retinitis, hepatitis, colitis, pneumonia, or encephalitis).

Infants born to mothers infected with CMV during pregnancy may develop congenital CMV infection.

Health-care professionals diagnose CMV infections by culturing the virus, detecting CMV DNA from the infected individual, or detecting CMV antibodies.

Antiviral treatments may improve the prognosis in some patients with cytomegalovirus infections.

There is no commercially available CMV vaccine. Experimental vaccines are being studied.

https://www.medicinenet.com/cytomegalovirus_cmv/article.htm

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Virus classification
Group: | Group I (dsDNA)
Order: | Herpesvirales
Family: | Herpesviridae
Subfamily: | Betaherpesvirinae
Genus: | Cytomegalovirus
Type species
Human cytomegalovirus

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The standard laboratory test for diagnosing congenital CMV infection is PCR on saliva, with urine usually collected and tested for confirmation.

because most CMV seropositive mothers shed CMV virus in their breast milk.

cause a false-positive CMV result on saliva collected shortly after the baby has breast fed.

Specific steps for appropriate collection of saliva samples from a baby :

1. Saliva collected more than one hour after breastfeeding and within 3 weeks of birth - because detection of CMV after 3 weeks could be the result of post-partum infection.

2.  a sterile cotton or polyester swab insert into the baby’s mouth between the gum and cheek and swirl for several seconds.

3. Remove the swab and place into buffer formulated for PCR diagnostic testing . If CMV is present, it will leach from swab to the liquid.

4. The liquid is processed according to manufacturer’s instructions, and PCR testing is performed according to the protocol in the laboratory.

5. Specific procedures and interpretation of tests vary according to laboratory.

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CMV IgM detection. CMV infection was diagnosed by the detection of CMV-specific IgM in serum samples (Eurogenetics CMV IgM ELISA assay). Patients were only included in the study if they had CMV-specific IgM levels of >300 U/mL in the absence of Epstein-Barr virus, hepatitis A, antibody to hepatitis B core antigen, and Toxoplasma gondii IgM antibodies and of rheumatoid factor.

CMV IgG avidity. The specificity of our CMV IgM assay was verified by performing CMV IgG avidity tests on all available samples from the study by using a modified CMV IgG EIA (Biokit) and 8M urea.

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Viruses in Cytomegalovirus are enveloped, with icosahedral, Spherical to pleomorphic, and Round geometries, and T=16 symmetry. The diameter is around 150–200 nm. Genomes are linear and non-segmented, around 200kb in length

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you probably can catch CMV  by touching your eyes, mouth or nose after contact with infected person through
*saliva
*semen
*vaginal fluids
*blood
*urine
*breat milk
*organ transplants

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Getting a Diagnosis

There are tests to check your blood and urine to see if there's any trace of the virus. For example, a serologic test looks for antibodies that your immune system makes to fight CMV. Your doctor can do a biopsy -- taking tissue or fluid from your intestine, throat, or spine -- and look at it under a microscope, too.

An eye doctor can check for inflammation in your retina.

Imaging tests, like a CT scan, give your doctor a picture of your lungs or brain that can show changes caused by CMV.

Treatment

When you have retinitis caused by CMV, your doctor may give you very strong IV meds for a couple of weeks, a process called induction therapy. For daily treatment, you may have a catheter put into your chest. After a while, your doctor may switch you to pills.

You might need medication injected directly into your eye if the virus is threatening your sight.

Once the infection is under control, you'll take a pill each day to keep it at bay.

Your doctor may prescribe drugs to keep the virus from making more copies of itself, including:

Cidofovir (Vistide)

Foscarnet (Foscavir)

Ganciclovir (Cytovene)

Valganciclovir (Valcyte)

These drugs generally can't cure the disease if you have advanced HIV, but they can control it while your HIV infection is being treated with antiretroviral therapy (ART).

You could have side effects, depending on which medicine you take, including:

Low white-blood-cell count (neutropenia), which raises your chance for other infections

Feeling tired from low red-blood-cell count (anemia)

Getting queasy or throwing up

Rash

Lower testosterone levels

Kidney problems

Treatment for CMV is used less often now. This is because anti-HIV meds (antiretroviral therapy, ART), when given early in the course of HIV infection, will prevent progression to advanced HIV and will keep you from getting CMV disease in the first place.

Prevention

CMV was once the most common viral opportunistic infection linked to HIV. Now, correctly taking antiretroviral therapy (ART) can help keep your CD4 count up and your immune system strong. It can also help stop retinitis from coming back.

If you have advanced HIV, in addition to ART, your doctor might give you medicine to prevent CMV, but it's expensive, sometimes causes severe side effects, and may not work well.

Whether you have advanced HIV or not, washyour hands often, especially after contact with others' urine or saliva. If you're around young children, avoid touching urine and saliva and things that come in contact with them because little kids are more likely to carry CMV via these body fluids.

Use condoms when you have sex, including oral sex.

Talk to your doctor about the likelihood of picking up CMV if you're going to get a blood transfusion.

WebMD Medical Reference Reviewed by Jonathan E. Kaplan, MD on June 01, 2018

Sources

SOURCES:

CDC: "Frequently Asked Questions about CMV," "About CMV," "You Can Prevent CMV."

AIDS Treatment Data Network: "Cytomegalovirus."

eMedicine: "Cytomegalovirus."

American Academy of Family Physicians: "Cytomegalovirus."

UCSF Center for HIV Information: "Cytomegalovirus and HIV."

National Library of Medicine MedlinePlus Drugs & Supplements: "Valganciclovir."

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There are tests to check your blood and urine to see if there's any trace of the virus. For example, a serologic test looks for antibodies that your immune system makes to fight CMV. Your doctor can do a biopsy -- taking tissue or fluid from your intestine, throat, or spine -- and look at it under a microscope, too.

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Cytomegalovirus (CMV) (from the Greek cyto-, "cell", and megalo-, "large") is a genus of viruses in the order Herpesvirales, in the family (150-200nm in diameter [hiv virus 120nm]) Herpesviridae, in the subfamily Betaherpesvirinae. Humans and monkeys serve as natural hosts.

There are currently eight species in this genus including the type species, human cytomegalovirus (HCMV, human herpesvirus 5, HHV-5), which is the species that infects humans.

Diseases associated with HHV-5 include glandular fever, and pneumonia.[2][3] In the medical literature, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses

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The following precautions may help lower the risk of contracting CMV:

Hand washing regularly with soap and water

Avoid kissing a young child, including tear and saliva contact

Avoid sharing glasses and kitchen utensils, for example, passing round a drink

Dispose of diapers, paper handkerchiefs and so on carefully

Use a condom to prevent the spread of CMV via vaginal fluids and semen.

The CDC urges parents and caregivers of children with CMV to seek treatment as early as possible, whether it is medication or attending services such as hearing checks.

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Newborn babies

pregnant women

people receiving an organ transplant

people with a weakened immune system

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wash hands with soap and warm water:

before preparing, serving or eating food

after going to the toilet

after changing a baby’s nappy

after coming into contact with bodily fluids, such as semen or urine