Cytomegalovirus (CMV) is a ubiquitous double-stranded DNA virus belonging to the herpes virus family group with the capacity to establish life-long latency in the host.1
Human cytomegalovirus is a _ human herpesvirus HHV5 characterised by its restricted host range, production of nuclear as well as cytoplasmic inclusions, and its long life cycle. It is the largest known human herpesvirus, with a genome of about 230 kb.28
Cytomegalovirus (CMV) is a common cause of infections world- wide. Like other herpes viruses, primary infection is followed by lifelong latency, with episodes of reactivation when the virus can be transmitted again.2
The human cytomegalovirus (HCMV) or human herpes virus v is one of the major causes of congenital infections.8
Characteristics of the virus in human cells:
CMV characteristically produces cell enlargement with intra nuclear inclusions, which led to the early designation of the term ”cytomegalic inclusion disease.” Infected cells were originally described as ”protozoon-like” or like to owl eyes.5
Hiding and relapse of the disease:
herpes virus family group with the capacity to establish life-long latency in the host. Reactivations may occur regularly and reinfections .1
Like other herpesviruses, primary CMV infection is followed by the establishment of lifelong latent infection from which periodic reactivation is common.11
It is not clear whether transplacental transmission of CMV in women with preexisting seroimmunity is secondary to virus reactivation or to infection with a new or different CMV strain (reinfection) during pregnancy.7
Congenital cytomegalovirus (CMV) infection is one of the most common viral causes of congenital infections in high resource countries, and a leading cause of hearing loss and a contributor to neurodevelopmental disabilities in children.1
CMV is the most common and serious congenital infection, because it occurs after both primary and recurrent infection in pregnancy and is a major cause of childhood deafness and neurological handicap.8
Congenital CMV infection is most likely to occur following a primary infection in the mother during pregnancy.11
The presence of actively replicating CMV during pregnancy, whether from primary infection, reactivation from latency or reinfection, can result in congenital transmission to the fetus. Congenital infection with CMV is a major cause of sensorineural hearing loss and neurological impairments.13
The most important burden of disease comes from CMV infections during pregnancy that can lead to infection of the unborn child. Worldwide, between 0.2% and 1.0% of all newborns have a congenital CMV infection, which can cause severe and long-lasting disability including sensorineural hearing loss and cognitive or motor developmental delay.2
More importantly, 5–10% of congenitally infected neonates have symptoms of irreversible CNS involvement in the form of microcephaly, encephalitis, seizures, deafness (a solitary finding in 10% of cases), upper motor neuron disorders, psychomotor retardation, and, rarely, myopathy and choroidoretinitis.15
Microcephaly alone does not confer as poor an outlook as hard neurological signs. These newborn babies also display other clinical features, including intrauterine growth retardation, jaundice, hepatosplenomegaly, thrombocytopenia, petechiae, and hepatitis, which tend to be self-limiting and resolve without treatment.28
The course of infection in healthy individuals is mostly asymptomatic, but CMV is a major cause of morbidity and mortality in immunocompromised individuals. The spectrum of disease expression is broad, with CMV receptivity of nearly all organs for example, in normal hosts there is development of a mononucleosis syndrome with persistent fever, myalgia, and cervical adenopathy and complications such as hepatitis, vasculitis, involvement of the respiratory tract and the heart (pericarditis, dilatative myocarditis), the gastrointestinal tract (esophagitis, gastritis, ulcerative colitis, pancreatitis), or the central nervous system (CNS; aseptic meningitis, encephalitis) including severe ophthalmologic complications (uveitis, necrotisizing chorioretinitis). 4
CMV infection acquired by blood transfusion may lead to significant complications inimmunocompromised individuals. Severe disease including pneumonia, retinitis, hepatitis, encephalitis, and other organ involvements due to CMV in immunocompromised patients have been reported.14
In immunocompetent persons, adequate humoral and cellular immunity are required to restrain viral replication after primary infection and to maintain HCMV in a lifelong chronic state. Persistent cytomegalovirus infection could elicit the seemingly preferential expansion of HCMV-specific clones and lead to HCMV-related inflammation, which is harmful to adults, especially the elderly.9
Cytomegalovirus replication can be detected in healthy cytomegalovirus-seropositive individuals affected by surgery-related stress, sepsis, and catecholamine release. Such conditions are typical soon after allogeneic solid-organ transplantation, in the context of immunosuppression to prevent organ-rejection, result in a heightened risk of cytomegalovirus replication and ensuing disease. Despite improved treatment and surveillance, cytomegalovirus continues to be a great cause of morbidity. Furthermore, virus-associated disease and virus-associated post-transplant complications remain an important economic drain on individual transplantation programmes.28
CMV is transmitted by close contact between individuals, through contamination from urine, saliva, semen, cervical secretions and breast milk, while droplet contamination is less significant.1
Transmission is possible via blood, sexual contact, breastfeeding, and organ transplantation.2 2
Studies have identified two sources of maternal CMV infection: sexual activity and contact with young children.3
In addition, CMV can be transmitted vertically through the placenta. Several CMV transmission routes have been clearly demonstrated. During childhood, these routes include mother-to-child via breastfeeding, parents- or siblings-to-child via close contact, or child-to-child via close contact in out-of-home settings such as day care centers.6?2
Close or even intimate person-to-person contact is believed to be required for the horizontal spread of these viruses. Primary infection is possible via blood transfusion or organ transplantation. CMV is excreted in nearly all secretions of the human body, such as blood, urine, feces, tears, saliva, breast milk, cervical mucus (CM), and semen. CMV survives in frozen and thawed semen (to the surface of spermatozoa, and sexual transmission is consideredas a major route of infection with CMV.4
Transmission occurs through direct contact with infectious bodily fluids such as saliva and urine Molecular epidemiology studies have demonstrated horizontal transmission among children and from child to Mother.3
Acquisition of the virus arises progressively from an early age, and in developed countries the overall seroprevalence is 30–70%.3 Homosexual men, poor socioeconomic groups, and residents of developing countries, however, have seroprevalence rates that can
CMV infections are endemic and lack seasonal variation. The seroprevalence is due to many factors such as hygienic circumstances, socio-economic factors, breastfeeding and sexual contacts and increases with age. The variation in the sero prevalence in different populations, including pregnant women, has been reported to be 35-95%.1
In populations from low resource countries, most children will acquire a CMV infection during the first years of life and the seroprevalence in children from high socioeconomic populations, breastfed for more than 6 months, is higher than in children breastfed for shorter periods. As a consequence of the variation in seroprevalence between countries, the prevalence of congenital CMV also varies between 0.15 – 2.0%.1
Non primary infections may represent reactivation of a latent infection or reinfection with a new strain of virus. In reproductive age women, seroprevalence rates range from 40 to 83%.24
Ganciclovir is both myelosuppressive and might induce viral resistance, and the purpose of a pre-emptive strategy for cytomegalovirus is to restrict ganciclovir exposure to thosepatients who have detectable cytomegalovirus reactivation.28
Study population and study design:
Through a cross-sectional study design, we studied reproductive women in a public primary health care center in karaj. City in 1396. Inclusion criteria for enrollment in the study were: 1) reproductive women; 2) residing in karaj City; 3) aged 15 years to 49 years; 4) who accepted to participate in the study.
In this study, the number of participants was 360 volunteers from women of childbearing age selected randomly. In this study, the formula for n = z²pq / d² was used to calculate the minimum sample size (z = 1.96, p = 80%, q = 5 %). For data analysis, SPSS software was used. Chi-square and Fisher were used to test the relationship between variables. First, a questionnaire including demographic data such as name, surname, age, place of birth and educational status, history of blood transfusion, history of transplantation, specific disease history, and information about CMV viruses were filled. Details of the work were done with respect to ethical considerations and satisfaction. Then, 5 ml of blood was taken and after serum separation by centrifugation, the serum were frozen at minus 20 ° C for the duration of the ELISA test.
Serum samples were obtained from each reproductive women by centrifugation of whole blood. Sera were examined for anti-CMV IgG antibodies by a commercially available enzyme immunoassay “Cytomegalovirus IgG (CMV IgG)” kit (Acon Biotech Co .Ltd) and for anti-CMV IgM antibodies by a commercially available enzyme immunoassay “Cytomegalovirus IgM (CMV IgM” kit (Acon Biotech Co .Ltd).
After completing the ELISA sampling, the Acon-Biotech kit and the ELISA Reader Stat fax 4200 were used. In this test, the cut-off kit was calculated, and those whose ODs were less than cut-off were considered negative and those whose ODs were higher than cut-offs was considered positive.
The tests were performed following the instructions of the manufacturer. The cut-off values for IgG and IgM seropositivity were obtained. A sample was considered positive for IgG or IgM when a CMV G index or a CMV M index was greater than 1.1, respectively.
In this study The total number of participants was 360.The average age of participants was 28.26 (SD: 6.34), at least 14 and up to 48 years old. Of these, 51 were under the diploma, 123 are diplomas, 44 were Associate’s degree, 116 were experts, 23 were masters and 3 were doctors.
The evaluation of IgG concentration is indicated in fig.1 .
fig.1 The IgG concentrations in all samples
According to the cut-off determined by the kit, which is 16.5 (in the figure with the dotted line), 360 of the tested specimens are positive for 280 and IgG negative for 80. The IgG prevalence in the specimens is shown in table.1.
table.1.The IgG prevalence in the specimens is showed
Positive Negative Prevalence Lower CI Upper CI
IgG 280 80 0.77 0.73 0.81
In order to study the relationship between the prevalence of CMV IgG and the levels of education, the samples were examined which the results are shown in fig.2.
Fig.2.the relationship between prevalence of CMV IgG and the education levels
The Chi-square test was used to compare CMV IgG between educational levels and the results showed that the observed difference between groups was not statistically significant (p = 0.59).
On the other hand, The IgM prevalence in the specimens was zero, which is shown in table.2.
table.2. IgM prevalence
Positive Negative Prevalence Lower CI Upper CI
IgM 0 0 0.013
A Fisher’s comparison test was used to compare IgG CMV between two age groups. The results showed that the observed difference between the two age groups was not statistically significant (p = 0.79).Fig.3.
Fig.3.Distribution of CMV seropositive women, according to age group.
In order to find the association between the prevalence of IgG and age of CMV, the samples were divided into two groups of 30 and over 30 years of age and were evaluated for IgG prevalence. Table.3.
table.3.Compare CMV IgM between two age groups
< 30 156 43
> 30 124 37
The chi-square test was used to compare CMV IgG between educational levels and the results showed that the observed difference between groups was not statistically significant (p = 0.59).table.4.
Table.4. Anti- CMV IgG Seropositivity rate by educational levels.
Associate 35 9
Bachelor 85 31
Diploma 97 26
Master/Doctoral 20 6
Under g. 43 8
In this study, the mean age of the participants was 26.28 years, out of a total of 360 participants, 51 under-diplomas, 123 diplomas, 44 Associate students, 116 Bachelor, 23 Master and 3 Ph.D. The results show that 77% of the subjects (280 out of 360) have CMV infection and have already been infected with the virus.. Table 1 .. Also, none of the participants had CMV-IgM antibodies. There was no significant difference between the educational levels and the age group of 30 and under 30 years of age and the infection rate with CMV.
This study revealed that the prevalence of CMV in reproductive women is very high, anti-CMV IgG antibodies were found in 280 of the cases, while 0 of the subjects tested positive for anti-CMV IgM.
The detection of CMV IgG indicated that the reproductive women had previously been infected with CMV. After CMV infection, IgG remains in the body for life and protects considerably against the next infections. This indicates that a negative result of CMV IgG test means that the women have not been infected with the virus.
Cytomegalovirus is one of the important members of the Herpesviridae family, and most people having an experience of contact with it. This virus is often found in the latent form, however, it has the capability of recurrence. Infection with this virus usually happens by means of blood transfusion and contaminated liquids of the body, such as urine, saliva, tears, milk, semen and vaginal secretions.
Intrauterine infection by cytomegalovirus virus is common in some countries such as America and various studies have reported the prevalence rate of this infection as 0.4 to 2.4%. The complications of infection with virus include microcephaly, brain calcification, Corytroinitis, Thrombocytopenia, hearing impairment, Hepatoplaningomaly and ocular anomalies. Young mothers who are negative for CMV infection are at increased risk and mothers who are infected by cytomegalovirus for the first time during their pregnancy usually transmit the virus to the fetus, which can have teratogenic effects. The prevalence of this virus depends on multiple factors like economic factors, age and geographical location of the population.
On the basis of previous studied, the prevalence of infection is about 40-100% .18
Seroepidemiological studies have shown that Cytomegalovirus infection is common and the prevalence of infection increases with age. The distinction between primary infection and secondary infection is very important because acute primary infection is transmitted to the fetus almost in 40% of cases and can lead to severe complications, while recurrent infection causes infections of fetus in 0.1-10% of cases. Moreover, since IgM might be found in primary and recurrent infection, measurement of IgG binding incline (IgG avidity) is a valuable method for confirming the initial infection of Cyteomegalovirus.26
CMV entrance to body motivates humoral and cellular immune responses that play important role in limit the infection. Although antibody reduces the severity of disease and it can effective in prevention, it’s possible to cause confusion in distinguishing the different stages of the disease and resulted in using different serological methods for primary infection, infection recurrent and recovery stage. 18
IgM reaches its peak early in infection and disappears 12 to 16 weeks after emergence of infection without any clinical symptoms. IgG reaches its peak about one month after infection and is predominantly of IgG1 and IgG3 types. The antibody produced in the serum prevents reinfection, but it does not prevent the activation of the latent viral infection. It might happen that the latent virus remain in the body of individual some years after the initial infection and reactivate and multiply in certain conditions such as blood transfusion and other irritants factors. 18
Concerning the necessity for pregnant mothers’ health and the role of CMV virus in the emergence of fetal abnormalities and major central nervous system disorders such as deafness, mental retardation, ocular disorders and etc., the aim of this study is to determine the seroprevalence of Cytomegalovirus infection in women of reproductive age referring to Sabze Parvar clinic of Karaj. The results of this study showed that most women of reproductive age who participated in this study had 77% positive antibody titers against cytomegalovirus and all of them were negative in respect to IgM antibody titers.
Several studies have been carried out on the association of Cytomegalovirus and recurrent abortions in different parts of the world. In Orang Ilami et al study (2013) in Yasuj, 98.9% of women of reproductive age had positive IgG antibody titer against cytomegalovirus and all were negative in respect to IgM. 26
In Arabzadeh et al study in 2007 in Kerman, prevalence of LgG antibody against cytomegalovirus was 91.94% positive and the prevalence of LgM antibody against Cytomegalovirus of 33.8% of samples was positive. 29
Hejazi et al (2006) studied the prevalence of antibodies against Cytomegalovirus in blood donors in Uremia. All studied serums (100%) of donors were positive for IgG against Cytomegalovirus and 2.8% of IgM samples were positive against Cytomegalovirus. 29
In Qafarian et al study (2014) on the blood donors, 98.8% of samples contained anti Cytomegalovirus IgG antibody and 5.5% contained anti-cytomegalovirus IgM. 30
In Skild et al study in 2005, the relation between anti-cytomegalovirus IgM and IgG antibody and intrauterine fetal death and it was found that 72% of the patients group and 69% of the control group were positive for IgG antibodies.29
In a Tayebi et al study in 2009 on female students of Islamic Azad University of Kazeroon, 94.4% of the subjects had anti-CMV anti-IgG antibodies. In a study conducted in Tehran Blood Transfusion Organization in 2004, the prevalence of anti-cytomegalovirus IgG antibodies was reported to be 89.6% and anti-cytomegalovirus IgM antibody was 0.04%. In a study conducted on pregnant women in Tehran, the prevalence of CMV IgG was reported to be 100%; while CMV IgM was not detected in any one. In a study that was conducted on healthy blood donors referring to Blood Transfusion Organization in Kashan, the prevalence of IgM was reported to be 2.3%. A study done in Tehran has estimated the prevalence of CMV IgG in women younger than 20 years as 98% and in women older than 20 years as 100%.
In a study in Saudi Arabia, the prevalence of CMV IgG was reported to be 92.1%. In a study in France which was carried out on healthy blood donors, 97.94% of the subjects had CMV IgG. 18
In a study in United States, the prevalence of cytomegalovirus in women of reproductive age has been reported to be 40-83% .24
In overall, the results of the present study on high prevalence of positive CMV IgG antibodies match with the results of other studies in Iran and elsewhere in the world indicating previous confrontation of individuals with cytomegalovirus and the widespread dissemination of this infection in the community.
The presence of anti-cytomegalovirus IgG antibody indicates that the individual has been infected by tis virus at a time after birth and this antibody remains in human body for his whole life. It should be noted that the antibody cannot prevent recurrence, re-activation of being infected by an infection with external and congenital origin. However, in cases of previously infection of mother and getting immunity, the risk of incidence of congenital infectious by cytomegalovirus and the infection of infant is greatly reduced.
The prevalence of CMV infection in this study is determined as 77%, which is close to studies conducted in Iran and elsewhere in the world especially in developing countries. Given the clinical importance of the diseases caused by cytomegalovirus and lack of comprehensive information on seroepidemiology of this virus, as well as the prevalence of congenital infections of cytomegalovirus in Iran, it is required to perform more cross-sectional studies. Moreover, performing studies with molecular methods such as PCR could be a useful and beneficial method for virus identification.
In the mentioned questionnaire, in addition to demographic information of the subjects, a question was asked about the familiarity or rate of information of the participants about the disease that could be considered as one of the variables of health literacy. However, health literacy is a collection of cognitive and social skills that determines the motivation and ability of individuals to obtain and access information, understand and use them to promote and maintain the health of individuals. Nowadays, health is now introduced as a global issue and due to its significant role on the decision making of individuals on areas related to health, it has been considered by policymakers as an essential instrument for promotion of the health level of community and increasing the quality of presented health care service. Although it is still not clear how health literacy affects health outcomes, many undesired outcomes concerning the health could be due to inadequate health literacy such that researchers believe that health literacy is stronger predictor of individual’s health compared to variables such as age, income, employment status, education level and race. Individuals usually have little knowledge about methods for prevention of diseases and they rarely participate in health care programs against chronic diseases. The global health organization has identified health literacy as one of the greatest determinants of health. In definitions of health literacy, its multi-dimensionality is usually mentioned and the ability of individuals in understanding and interpreting the meanings and concepts of health information is defined in various forms. Moreover, it is about the skills and capacities emerging in acquisition and getting medical and health information in their perception, processing, interpretation, decision making and application of this knowledge and the skills and capacities that are considered as the basis for evaluation in health literacy instruments. Concerning what has been mentioned, measurement of health literacy can be useful and necessary so that by designing special interventions to increase it, it becomes possible to prevent the risk due to limited literacy since people with lower health literacy are more likely to evaluate their own health as weak after conforming age, gender, race and indicators of economic deprivation. 31 In our study, one of the questions was to measure the information of individuals about the cytomegalovirus and the diseases caused by this infection which all the participants had no information about it. Moreover, some questions were asked of participants about the history of blood transfusion, history of transplantation; history of special disease and none of the participants responded positively to the above questions.
Hereby, I thank Dr. Ali Ehsan Heydari and everyone who voluntarily participated in this study.