Identification
CMV is a commonly encountered virus that affects the population of any age category. CMV causes a latent infection, commonly asymptomatic. The infection with this virus often escapes undiagnosed. Primoinfection occurs in childhood and CMV persists all life in a dormant state without replicating; But under certain conditions it can be reactivated. It is estimated that 50-80% of adults are infected with CMV until the age of 40 years. CMV is the most common viral congenital infection, and the most common viral cause of mental retardation, but also the main nongenetic cause of neuro-sensitive deafness. The most severe form of disease occurs in 5-10% of intrauterine infected infants. They present signs and symptoms of severe generalised disease, involving primarily the central nervous system and the liver. Lethargy, convulsions, jaundice, petechiae, purpura, hepatosplenomegaly, corioretinitis, intracerebral calicifications and pulmonary infiltrations may appear initially. Survivors exhibit mental retardation, microcephaly, motor handicap, hearing loss. Fetal infection may occur during primary infection (first date) of the mother and then the risk of transmission is very high or during the reactivation of the infection (the risk of maternofetal transmission is lower).
The Primoinfection is accompanied by repeated viremia, CMV which can pass transplacental.
If primoinfection occurs before the woman gets pregnant, the risk of transmitting the cytomegalovirus to the fetus is 1%.
The infection of the pregnant women is most commonly asymptomatic. If it is symptomatic, the Primoinfection (primary infection) in pregnant may manifest itself in several forms:
A.) Prolonged febrile syndrome with high fever (38-40 ˚ C) on the plateau, which persists over 15 days
B.) Non-Epstein Barr mononucleosis syndrome: Fever, Aden-Hepatosplenomegaly, lymphomonocytosis with atypical lymphocytes
C.) subclinical hepatitis (hepatic cytolysis without jaundice)
Among the tasks with CMV infection confirmed, only 10-20% of foetuses will have clinical manifestations at birth.
Mothers who are seropositive before pregnancy may transmit to the fetal CMV during the reactivation of the existing latent virus in the body (especially in the salivary glands) or reinfection with a new strain. The infections transmitted thus are usually asymptomatic and less severe, both for the mother, especially for the fetus, causing sequelae in the case of 0.2 to 2% of children.
The age of pregnancy at the time of Primoinfection has an important effect on intrauterine transmission and on symptoms at birth.
Although the risk of CMV transmission to the fetus is large in the third quarter, newborns are asymptomatic both at birth and later.
Overall, 80-90% of CMV-infected newborns are asymptomatic at birth.
Of the asymptomatic, 10-15% will exhibit developmental disorders, especially deafness. Correlating with the age of pregnancy at which Primoinfection occurred, 30% of newborn infants from infected mothers in the first trimester will develop neurological sequelae, and 15% of newborn infants from infected mothers later during pregnancy.
The symptomatic CMV infection is manifested in 50% of cases with isolated splenomegaly, jaundice and/or petechial, and the remaining 50% of cases are presented with the manifestation called classic “disease with cytomegalic inclusions of the newborn” which includes plurivisceral and neurological signs and symptoms:
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The prognosis is poor for symptomatic newborn babies: mortality is approximately 30% and 80% of survivors manifest sequelae: deafness, ocular impairment, intellectual disabilities, retardation in psychomotor development.
Neuro-sensitive deafness is detected in over 60% of newborns with symptomatic congenital CMV infection, being progressively up total.
Children with symptomatic congenital CMV infection should be monitored periodically by conducting screening tests for hearing, vision and psychomotor development.
The transmission of the infection during childbirth is very rare and is either asymptomatic or manifested with a syndrome similar to mononucleosis infectious.
Diagnosis of CMV infection in pregnant
The maternal CMV infection is commonly asymptomatic, therefore clinical diagnosis is almost impossible.
- Serological diagnosis
In most cases, maternal seroconversion is sufficient for the diagnosis of primary infection. This is defined as the modification of IgM antibody titer from negative to positive, or an increase of 4-6 times of IgG titer over a period of 6-8 weeks.
Seroconversion’s surprise is the only definite evidence of primoinfection.
However, there are difficulties in the serological confirmation of Primoinfection CMV, so, anti-CMV IgM may persist several months after primoinfection, may occur during reactivations and do not always appear at Primoinfection.
The anti-CMV IgG avidity test for viral antigens can determine the type of infection, recent (low greed) and old (high-greed).
The diagnostic technique with the utmost accuracy is Western Blot.
- Virological diagnosis
It is achieved by isolating the virus in cell cultures and/or highlighting viral DNA through PCR in various pathological products. The presence of viremia implies an increased risk of transplacental transmission, however, does not preclude the possibility of not transmitting because primoinfection is characterized by a short period of viremia.
Also can be performed the quantitative appreciation of Antigenemia PP65, the presence of pp65 antigen is similar to the presence of the virus in the bloodstream.
Diagnosis of CMV infection in the foetus (intrauterine)
In case of confirmation of the maternal CMV infection it is important to assess the risk of transmission to the foetus.
Perinatal ultrasound can be useful, identifying structural or growth anomalies that may suggest a symptomatic fetal infection.
Ultrasound anomalies suggestive of congenital CMV infection: ventriculomegaly, microcephaly, hyperecogenic fetal bowel , hepatosplenomegaly, intracerebral calcification, intrauterine growth retardation, abnormal volume of amniotic fluid, Increased placenta, ascites and fetal hidrops. These changes are not specific to CMV. In addition, only 15% of foetuses infected with CMV will present these anomalies. However, their presence in a pregnant woman with a confirmed primary CMV infection is highly suggestive for the infection of the fetus.
In cases where maternal infection is detected in the first half of pregnancy or ultrasound anomalies suggestive of CMV, amniocentesis may be used to confirm fetal infection, but not earlier than 21 weeks when they may False negative results appear (fetal kidneys may not excrete the virus in sufficient quantity to be detected).
In performing amniocentesis, viral and PCR cultures will be carried out, which if they are positive cannot determine the impact on the fetus. For more information about prognosis, RT-QPCR and fetal thrombocytopenia detection can be achieved.
Diagnosis of CMV infection in newborn
Postnatal infection should be confirmed by isolating the virus in urine and/or saliva within the first 10 days of life. It can be diagnosed by the demonstration of CMV in the CSF by PCR or the demonstration of CMV in the placenta.
Serological diagnosis is subject to errors, as only 70% of infected newborns have positive IgM antibodies.
It should be noted that a positive diagnosis of congenital infection with CMV does not equate to the impaired fetus, known as 80-90% of foetuses are asymptomatic at birth.
Infectious Agent
Human herpes virus 5 (Beta) – Human CMV, of the subfamily Betaherpesvirinae, the from Herpesviridae family; Includes 4 major genotypes and many strains.
Incidence and prevalence
In the US, approximately 30-50% of women are not infected with CMV, and 1-4 of 100 women who have not been infected with CMV do primoinfection during pregnancy. The risk of transmission to the foetus is 30-40%. In developed countries, the congenital CMV infection has an incidence of 0.3-2.4 cases at 100 births.
In developing countries the situation is not well defined but the presence of anti-CMV serum antibodies in young adults can reach up to 100%.
Source
The natural reservoir is strictly human, the stems from the animal cannot infect the man.
Most commonly uninfected women can contact infection from infected children.
Method of transmission
Transmission implies the existence of close interhuman contact. The rate of transmission is increased in households with small children or children’s centers; in children’s centers the rate of excretion of cytomegalovirus can reach 70% for children aged between 1 and 3 years.
The transmission pathways are: respiratory (most common), sexual, through saliva, breast milk or urine, transplacental, blood transfusion or organ transplant.
For pregnant women, the most common pathways of CMV contamination are sexual contact and contact with urine and saliva of infected children.
Risk groups
Young adults who have not yet come into contact with the virus.
Pregnant women working in care centers of small children, nursery, kindergartens, primary schools.
Seronegative infants who receive milk from an infected surrogate mother.
People who have undergone blood transfusions or organ transplants. Any person with immunosuppression: AIDS, cancer, autoimmune diseases. Gay men with multiple partners.
Incubation period
In the infection occurring for example following an organ transplant or blood transfusion is around 3-8 weeks. The acquired infection during delivery is demonstrable at 3-12 weeks after birth.
Infetiousness Period
The virus is excreted in urine and saliva for several months and may persist or occur episodicly for many years after the primary infection. After neonatal infection, the virus can be excreted for 5-6 years. The virus once entered the body persists the whole life, the infection is latent. Less than 3% of healthy adults are pharyngeal excretive. Excretion occurs with immuonosuppressia and immunodeficiency.
Prophylaxis
In the absence of a vaccine, attention should be directed towards educating patients as a primary means of preventing infection. Because between 15 and 70% of children in care centers (kindergartens, crèches) are infected with CMV, prevention should be addressed to mothers of young children. Women seronegative for CMV have been shown to have a 5-35-fold higher risk of developing the infection if they come into contact with children in these centres.
Knowing the personal susceptibility of pregnant women through screening can be useful in adopting strategies for preventing CMV infection.
The American College of Obstetricians and Gynecologists (ACOG) recommends that all women be educated about methods of preventing CMV infection. At the same time, it recommends careful handling of potentially infected items such as disposable diapers, and persistent hand washing (with water and soap for 15-20 seconds) after contact with young children, especially after the change Baby, wiping the baby’s nose and handling toys.
The CDC confirms the recommendations of the ACOG and adds that pregnant women with children under the age of 6 should be advised not to use jointly-eaten utensils, not to share food or drink with children and to avoid kissing children on the cheek or lips, to clean up Toys and all surfaces that come in contact with urine and children’s saliva. Despite these recommendations, a recent study by ACOG reports that only 44% of obstetricians-gynecologists advise their patients on the prevention of CMV infection.
Although the CDC does not recommend the routine screening of women pregnant for CMV, it admits that for women planning to become pregnant screening routine of the CMV infection it is useful to understand individually how much attention should be given to Prevention of CMV infection.
The reasons why it is not recommended to screening pregnant women are: difficulty in obtaining a high accuracy diagnosis under the conditions of a high rate of false-positive results when using the trade tests for IgM, the lack of an effective treatment during pregnancy, the possibility of reinfection or reactivation in the case of HIV positive women.
Additional tests are required to confirm primary infection (the avidity test or Western Blot) in order to properly assess the foetal risk but also to provide advice to pregnant women to prevent anxiety that may result from the extension of screening tests at national level.
At the same time, it is necessary to evaluate correctly and seriously the severity of the diagnosis of a mother-to-CMV infection and discuss the option of termination of pregnancy, based on the definite confirmation of fetal infection.
Vaccination
There is currently no vaccine available.
Administration of anti-CMV immunoglobulins
It is possible to administer anti-CMV immunoglobulins in combination with antiviral medicines in the treatment of immunodeprimated people.
Birth to the woman infected with CMV
The postnatal disease with CMV may occur in infants born of CMV-carrying mothers in cervical secretions at birth; Thus the transmission of the virus from the infected cervix to birth is a common way of neonatal infection.
The transmission of the infection during childbirth is very rare and is either asymptomatic or manifested with a syndrome similar to mononucleosis infections.
There’s no C-section recommendation.
Breastfeeding
The virus can be transmitted to infants through infected breast milk, an important source of infection, but not the disease, unless the milk of a surrogate mother is given to infants seronegative.
Treatment
Choice medicines for prophylaxis and treatment of CMV disease are the Ganyiclovir IV and the Valgancyclovir, oral administration. A controversial drug remains Maribavir.
About Corneliu Zaharia
