Virus Introduction


Virus Introduction:
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.28Cytomegalovirus (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
Clinical symptoms:
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.2More 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
Transmission:
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
exceed 90%.28
Epidemiology:
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
Treatment:
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
Materials &methods:
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.

Laboratory tests:
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.
Results:
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
IgG280 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
IgM0 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
Positive Negative
< 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.

Positive Negative
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.