Hospital Infection Control

Viruses - cytomegalovirus

What are the key principles of preventing viruses - cytomegalovirus?

If a pregnant woman acquires a primary infection with cytomegalovirus (CMV) the fetus is at high risk for congenital disease. This plus the fact that acquisition of a CMV infection causes death and disease in low birth weight infants, immunocompromised patients, and transplant recipients, means there is concern about the possible transmission of CMV within hospitals. To interpret studies of CMV transmission within the hospital, one must understand CMV transmission in the population.

Diagnosis and clinical features

A transient viremia occurs after a primary infection with CMV. Among immunocompetent individuals a primary CMV infection is usually asymptomatic but occasionally in adults may cause an infectious mononucleosis syndrome with fatigue and low-grade fever. Among immunocompromised patients CMV may cause severe disease in many organs and reactivation of latent CMV infections is common.

CMV infections are diagnosed by recovery of the virus from infected tissues or organs. Histological examination may reveal the CMV inclusion cells.

Epidemiology

Nearly all individuals eventually become infected with CMV. The percentage of seropositive individuals increases with age at a rate of approximately 1% or 2% per year, and a mean of about 50% of the United States population possesses antibodies to the virus. Nearly 100% of the population is seropositive by age 70 years.

The rate of excretion for any age group depends on geographic location and is variable. The congenital infection rate worldwide, however, is remarkably constant; in any population, between 0.5% and 2% of newborns will be excreting CMV.

Prolonged viral excretion in saliva and urine may persist for weeks or months. After infection, young children excrete CMV in saliva and urine for a period of 12 to 40 months, significantly longer than adults. Immunoglobulin G (IgG) antibodies to CMV appear 2 to 3 weeks following a primary infection and persist for life in both children and adults.

In up to 2% of all pregnancies, transplacental transmission of CMV occurs. Usually the mother is seropositive pre-conception, and the infants become congenitally infected in utero following a reinfection of the mother.

Although primary maternal infection during pregnancy accounts for only a small percentage of congenitally infected newborns, primary infection does account for the majority of the symptomatic infections and severe handicaps caused by congenital infection.

Breast milk transmission of CMV from seropositive mothers accounts for 50% of transmitted infections and 10% to 20% of transmitted infections occur via cervical and vaginal secretions. Also, CMV can be acquired postnatally from other children, as in a day care setting; intrafamilial transmission is frequent following a primary infection in a single family member, with a rate of transmission of about 50%.

CMV is frequently excreted in semen and cervical secretions and CMV infections are more prevalent among those who have multiple sex partners.

CMV is transmitted slowly. Children initially shed CMV at a concentration of about 104 plaque‑forming units per milliliter (PFUs/mL) of urine after a primary infection and this titer declines slowly thereafter.

The majority of children in day care become infected in the second year of life. Child-to-child transmission within day care centers is slow and on average only one child per month acquires a primary CMV infection. Therefore, even under ideal transmission conditions of close, intimate daily contact (i.e., children playing daily together in the same room), the virus is transmitted slowly.

The period for CMV transmission from infected children to their mothers or caregivers is also very slow and depends on the age of an infected child. Among the seronegative mothers and fathers of infected children 50% become infected within 8 months.

Caregivers may also be infected with CMV through transmission from children with the highest rate of CMV infections among women caring for children younger than 2 years independently of age. For caregivers the annual seroconversion rates range from 11% to 20% compared with a 2% rate for hospital employees.

What are the key conclusions for available clinical trials and meta-analyses that inform control of viruses - cytomegalovirus?

Prevention and control

CMV transmission from patients to hospital personnel occurs rarely, if at all, and has never been documented. An analysis of the seroconversion data shows that there may be an annual infections rate 1% to 4% greater for nursery nurses than for the general population but there are many problems with this anaysis.

CMV can be transmitted between hospitalized patients, but transmission is easily prevented. Soap and water readily inactivate the virus, and simple hand washing techniques should prevent transmission.

One study showed that susceptible pregnant women but not non-pregnant women could protect themselves from acquiring CMV from their infected child by following simple hygienic precautions. Thus if strictly adhered to, standard precautions will protect both patients and personnel.

One should not be concerned about patient-to-patient transmission unless dealing with immunocompromised patients or premature infants. One should be very careful about the kinds of contact these patients have with other patients and personnel; one should adhere to frequent and adequate hand washing techniques and to standard precautions.

It is not necessary to routinely test hospital personnel for CMV immunity either before or during pregnancy because of the low incidence of infection. If, however, a pregnant woman working in a health care setting is especially concerned about CMV, serologic testing for immunity can be done.

Seronegative pregnant women who are susceptible should be especially attentive to good hygiene at work and at home if they care for a young child at home. Serial serologic testing during pregnancy should be offered as an option to concerned pregnant seronegative health care workers.

Pregnant women also should not be furloughed or transferred with the idea that their exposure frequency would decrease on different units. They should assume that all patients might be infectious and are best advised to practice frequent hand washing and strictly adhere to standard precautions.

Standard precautions apply to blood and all body fluids, secretions, and excretions. Pregnant hospital personnel should assume that all body fluids are possibly infectious. As stated above, they should practice frequent hand washing after patient contact. When they perceive that they are most likely to be exposed to body fluids or when they are handling urine and respiratory secretions, they should wear gowns and gloves.

While CMV is seldom, if ever, transmitted via respiratory droplets, the polymerase chain reaction, a very sensitive method for detecting minute quantities of DNA, has detected CMV DNA in the filtered air near immunosuppressed patients with CMV pneumonia and other respiratory infections. Because the infectivity of aerosols from such patients is unknown, use of a mask by pregnant women is appropriate when prolonged or frequent exposure to aerosolized urine or respiratory secretions is likely to occur.

What are the consequences of ignoring key concepts related to control of viruses - cytomegalovirus?

There is a risk of transmission in the hospital if health care personnel fail to wash their hands after being in contact with the virus. The transmission could be to the health care worker or to other immune suppressed patients.

What other information supports the key conclusions of studies of viruses - cytomegalovirus e.g., case-control studies and case series?

Cytomegalovirus transmission in hospitals

Prevalence of cytomegalovirus excretion among hospitalized adults and children

Nearly all the hospital transmission studies have been conducted in pediatric units because children have higher excretion rates than adults as indicated by published reports on the prevalence of CMV excretion among hospitalized adults and children.

In a home care setting, 8% of children younger than 5 years excrete CMV. This rate increases to between 9% and 75% for children in day care depending on the day care center. Between 1% and 7% of hospitalized children beyond the newborn period shed CMV. From 1% to 3% of infants in newborn nurseries shed CMV at any time although an Egyptian study found 12.5% of 175 infants in a neonatal intensive care unit shedding CMV.

Viremia is rare among healthy adults and less than 1% is viruric. On a general oncology ward less than 1% of adult patients excreted CMV. Up to 45% of stem cell recipients may excrete CMV, but this percentage may be decreasing because of the selection of seronegative donors and the frequent use of ganciclovir.

Among AIDS patients, rates of CMV excretion vary widely, but it is probable that at least 25% of symptomatic patients will shed CMV. In the 1970s, between 38% and 96% of kidney recipients excreted CMV but current rates are probably much lower because immunosuppressive therapy is less intense. Finally, 8% to 35% of pregnant women will excrete CMV from one or more sites in the third trimester.

CMV infection at eight different hospital units in two children's studies found infection rates in the units ranged from 3% to 6%, but the chronic care units had much higher rates (15%) of CMV infection. In these units, the children were together for many months, were chronically ill, and had multiple blood transfusions.

Cytomegalovirus on surfaces

Where is CMV in a hospital besides in the urine and saliva of infected patients? One study obtained numerous surface swabs for CMV culture from toys, Ambu bags, scales, intravenous tubing, crib rails, and thermometers. The swabs did not recover CMV from any inanimate object. However, the virus was isolated on the hands of a patient, a nurse, and a laboratory worker. Hands are a known reservoir for CMV. In day care centers CMV is on the hands of children and caregivers.

It is easy to deactivate CMV with such products as soaps, detergents, and alcohol; CMV will also wash off surfaces with plain water. The virus is not very stable in the environment. CMV has a half-life of 2 to 6 hours on surfaces, but low titers of virus may persist for 24 hours.

Patient-to-patient transmission

Table I lists the published rates of CMV infection among pediatric nurses and control subjects (women without patient contact). Relatively low numbers of primary CMV infections and low numbers of total subjects have affected the results of each survey. One report in the early 1970s, observed infection in 3 or 21 ward nurses, 2 or 34 nursery nurses, and 0 or 27 control subjects. Studies in Sweden and Philadelphia showed similar results, but low rates of CMV infection were found in other studies.

Table I.

Rates of primary cytomegalovirus infection among pediatric nurses and control subjects
Ward nurses Nursery Nurses Controls (women without patient contact)
Authors Location (reference) Annual seroconversion ratea No. of nurses studied Annual seroconversion rate No. of nurses studied Annual seroconversion rate No. of women studied
Yeager et al. Denver, CO 7.7 (3/39)b 31 4.1 (2/49) 34 0 27c
Ahlfors et al. Malmo, Sweden 6.9 (2/29) 29 3.0 (1/33) 52
Dworsky et al. Birmingham, AL 3.4 (4/118) 61 2.3 (23/1,000) 1,549
Friedman et al. Philadelphia, PA 6.0 (7/117) 115 13 (3/23) 23 2.9 (1/35) 35
Adler et al. Richmond, VA 4.4 (2/45) 31 1.8 (1/55) 40
Demmler et al. Houston, TX 0 48c 6.5 (7/107) 70
Balfour et al. Minneapolis, MN 1 (2/200)d 117 2.2 (4/182) 96 1.8 (16/867 519
Balcarek et al. Birmingham, AL 2.3 (8/348)e 183 2.1 (4/191) 105
All studies 3.1 (24/778) 506 3.9 (21/534) 324 2.1 (45/2,126) 2,260

All the studies fund a low infection rate among the control subjects. When the infection rates (number of persons infected per 100 person years observed) for each of the studies listed in Table I were averaged, a higher annual infection rate was found among those who worked in pediatric hospitals than among the control subjects.

Ward nurses display an annual average infection rate of 3.1 infections/100 person years (24 infections for 778 person years); this does not differ statistically from the 2.1 infections/100 person years (45 infections for 2,126 person years) observed in the control group. In nursery nurses the average annual infection rate is 3.9 infections/100 person years (21 infections for 534 person years), which is a significantly higher rate than that observed in the control group (p <.05, chi square = 4.8, 1 degree of freedom).

The above analysis should be approached with skepticism for several reasons. First, the statistical analysis depends on the large group of pregnant women who served as controls in the Birmingham study. If this control group had not been available, the analysis would lack sufficient statistical power to detect small differences among groups.

Second, in three of the studies, nursery nurses did not acquire CMV from infected infants in their care, according to genome analysis data. This was true of one woman in the Richmond study, of two in the Birmingham study, and of two in the Houston study.

Third, one may be comparing very dissimilar groups when combining studies, because nurses engage in many different activities, and these activities and their relative frequencies may vary widely among hospitals.

Fourth, the highest rate of infection occurs in nursery nurses and these nurses care for children with the lowest rate of CMV excretion. Summarizing the data in Table I, under the worst circumstance the rate of CMV infection for nursery nurses is probably no more than three times higher than the rate for control subjects (relative risk = 1.83; 95% confidence interval = 1.01–3.04).

A powerful tool for studying CMV transmission is DNA genome analysis of viral DNA. Table II lists the results of studies that applied this technique to studies of CMV in the hospital. Between 1982 and 1985 one study monitored the number or children in the newborn nursery in Richmond who shed CMV and the periods they were viruric while hospitalized. Forty seronegative women were monitored. Of this group one seroconverted, but she shed an isolate that had a DNA genome pattern different from 34 of the isolates excreted by the children in the nursery for that period. Also, no infant-to-infant transmission occurred.

Table II.

Cytomegalovirus transmission studies using analysis of viral deoxyribonucleic acid
Number of Isolates studied Number of isolates
Authors Location (reference) Type of unit Children Nurses Different Identical
Wilfert et al. Durham, NC aNICU 1 1 2 0
Yow et al. Houston, TX NICU 1 1 2 0
Spector Oakland, CA NICU 7 0 4 3
Dworsky et al. Birmingham, AL NICU 1 1 2 0
Adler et al. Richmond, VA NICU 34 1 35 0
Demmler et al. Houston, TX Chronic care 24 3 25 2

In one report it was believed that a house officer had acquired CMV from a child in her care, but the DNA of her isolate differed from that of the isolate shed by the child. Surveys revealed similar observations for nurses elsewhere.

DNA analysis of viral isolates indicated that two babies in a neonatal nursery had probably acquired CMV from another infected infant in that nursery. Infants became infected after being located side by side for approximately 6 weeks. They received care from common caregivers but did not receive blood from common donors.

Another study reported the DNA patterns of 27 viral isolates, 24 from children and 3 from nurses, derived from 18 sets of samples obtained for culture from children and staff on a pediatric chronic care unit.

Four children produced two pairs of identical isolates. Because one pair of children had shared a common blood donor, it is uncertain if the CMV was acquired from the blood donor or via horizontal transmission. The second pair of children who shed identical isolates had been given care for 20 weeks or more side by side in the same unit, and they had not received blood from a common donor. One nurse had cared for both children for 3 weeks. Therefore, it is reasonable to assume that these children shed isolates with identical DNA patterns, because patient-to-patient transmission occurred.

Based on genome analysis there have been no documented instances of CMV transmission from patients to hospital caregivers, but in at least some of the cases cited above, patient-to-patient transmission probably did occur. In both cases, patient-to-patient transmission occurred in chronic care units with children crowded side by side for long periods; this is an institutional setting similar to that of day care.

Summary of current controversies.

In this author's opinion there are no current controversies regarding CMV hospital transmission.

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and viruses - cytomegalovirus.

See Table I. Rates of primary cytomegalovirus infection among pediatric nurses and control subjects.

See Table II. Cytomegalovirus transmission studies using analysis of viral deoxyribonucleic acid.

References

Demmler, GJ, Yow, MD, Spector, SA. "Nosocomial cytomegalovirus infections within two hospitals caring for infants and children". J Infect Dis. vol. 156. 1987. pp. 9-16.

Dworsky, ME, Welch, K, Cassady, G, Stagno, S. "Occupational risk for primary cytomegalovirus infection among pediatric health‑care workers". N Engl J Med. vol. 309. 1983. pp. 950-953.

Adler, SP, Baggett, J, Wilson, M, Lawrence, L, McVoy, M. "Molecular epidemiology of cytomegalovirus transmission in a nursery: lack of evidence for nosocomial transmission". J Pediatr. vol. 108. 1986. pp. 117-123.

Morgan, MA, el-Ghany, el-SM, Khalifa, NA, Sherif, A, Rassian, LR. "Prevalence of cytomegalovirus (CMV) infection among neonatal intensive care unit (NICU) and healthcare workers". Egypt J Immunol. vol. 10. 2003. pp. 1-8.

Hutto, C, Little, EA, Ricks, R. "Isolation of cytomegalovirus from toys and hands in a day care center". J Infect Dis. vol. 154. 1986. pp. 527-530.

Faiz, RG. "Comparative efficacy of hand washing agents against cytomegalovirus". Pediatr Res. vol. 20. 1986. pp. 227A.

Faix, RG. "Survival of cytomegalovirus on environmental surfaces". J Pediatr. vol. 106. 1985. pp. 649-652.

Yow, MD, Lakeman, AD, Stagno, S. "Use of restriction enzymes to investigate the source of a primary cytomegalovirus infection in a pediatric nurse". Pediatrics. vol. 70. 1982. pp. 713-716.

Spector, SA. "Transmission of cytomegalovirus among infants in hospital documented by restriction‑endonuclease‑digestion analyses". Lancet. vol. 1. 1983. pp. 378-380.

Adler, SP, Finney, JW, Manganello, AM, Best, AM. "Prevention of Child-to-Mother Transmission of Cytomegalovirus among pregnant women". J. of Pediatric. vol. 145. 2004. pp. 485-91.

McCluskey, R, Sandin, R, Greene, J. "Detection of airborne cytomegalovirus in hospital rooms of immunocompromised patients". J Virol Methods. vol. 56. 1996. pp. 115-118.

Yeager, AS. "Longitudinal, serological study of cytomegalovirus infections in nurses and in personnel without patient contact". J Clin Microbiol. vol. 2. 1975. pp. 448-452.

Ahlfors, K, Ivarsson, SA, Johnsson, T, Renmarker, K. "Risk of cytomegalovirus infection in nurses and congenital infection in their offspring". Acta Paediatr Scand. vol. 70. 1981. pp. 819-823.

Friedman, HM, Lewis, MR, Nemerofsky, DM, Plotkin, SA. "Acquisition of cytomegalovirus infection among female employees at a pediatric hospital". Pediatr Infect Dis. vol. 3. 1984. pp. 233-235.

Balfour, CL, Balfour, HH. "Cytomegalovirus is not an occupational risk for nurses in renal transplant and neonatal units". JAMA. vol. 256. 1986. pp. 1909-1914.

Balcarek, KB, Bagley, R, Cloud, GA, Pass, RF. "Cytomegalovirus infection among employees of a children's hospital". JAMA. vol. 263. 1990. pp. 840-844.

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