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Magnetic resonance imaging (MRI) at age of 4 years. (A) Axial T2-weighted sequence. Residual white matter hyperintensities (due to demyelination and gliosis) with periventricular location on both sides (yellow arrows) and persistent intraventricular septa, mainly in the occipital region (red arrow). (B) Coronar T2-weighted sequence. Residual periventricular hyperintense white matter lesions (yellow arrows).
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Cytomegalovirus (CMV) is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV) transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactiva...
Citations
... CMV envelope glycoproteins play a vital role in virus entry and cell fusion. CMV is transmitted through direct contact with infectious bodily fluids , such as tears, saliva, nasal secretions, vaginal secretions, urine, or breast milk, can transmit CMV ( Mack I et al., 2017). Human CMV infection is normally unrecognized in healthy people, but it can be lethal in people with compromised immune systems, such as HIV patients, organ transplant recipients, or infants. ...
Background; Viral infections are common around the world and cause many health problems. Infertility in men is a widespread health problem that can affect lifestyle and psychological state. Aims of the study; Study of the effect of herpes virus type 6 and cytomegalovirus on infertility disorders in men. Methodology; A case control study was done for a 100 specimens collected from men. This study has been conducted in Al Sader Medical City / Infertility Center / Al-Najaf Al-Ashraf and privet Center Dr. Ali Al-Ibrahimi for Embryos and Infertility in najaf . During the period from 10/10/ 2023 to 10/4/2024. The current study consisted of a sample size of 100 males, which was subsequently separated into two groups. The control group comprised 40 fertile men, aged 25 to 45 years, who had experienced both primary and secondary fecundity for at least twelve months. The Patients Cases group, consisting of sixty infertile males aged between 22 and 46 years, was categorized into two subgroups based on the type of infertility. There were forty-six guys who were classified as main infertility. There were a total of fourteen men who experienced secondary infertility. Male participants who are reproductive age, normal seminal analysis which is healthy and have a child as a Control group (Fertile men). Name of patient, sample number, Age (years), Education, housing area, Type of work, height, weight, Smoking, chronic diseases, History of surgery, Primary infertility, Secondary infertility, Sperm count, Sperm motility and Sperm morphology. Detection of CMV in semen plasma by CMV ELISA kit and detection of HHV 6 in semen plasma by HHV 6 ELISA kit. Result; The results showed that there was no statistical significance in age between the two groups. They also showed that there was statistical significance in smoking, type of infertility, and duration of infertility. The results showed statistical significance in the results for herpes and cytomegalovirus. There is also no statistical significance regarding the number of cases of cytomegalovirus infection according to age. On the contrary, there was statistical significance regarding age in herpes. The results also indicated that there was statistical evidence in the sperm analysis between the two groups. Conclusions; The statistical evidence between the two groups in the number of infection cases for all groups or by age indicates the role of viral infections in causing infertility in men.
... Only three other case reports were published in the last 10 years [14][15][16] about neonates with severe cCMV born by previously immune women. We compared them to our case (Table 2). ...
Background
Congenital cytomegalovirus (cCMV) infection, resulting from non-primary maternal infection or reactivation during pregnancy, can cause serious fetal abnormalities, complications in the immediate neonatal period, and severe sequelae later in childhood. Maternal non-primary cytomegalovirus infection in pregnancy is transmitted to the fetus in 0.5-2% of cases (1).
Case presentation
An African full term male newbornwas delivered by emergency caesarean section. Due to signs of asphyxia at birth and clinical moderate encephalopathy, he underwent therapeutic hypothermia. Continuous full video-electroencephalography monitoring showed no seizures during the first 72 h, however, soon after rewarming, he presented refractory status epilepticus due to an intracranial hemorrhage, related to severe thrombocytopenia. The patient also presented signs of sepsis (hypotension and signs of reduced perfusions). An echocardiography revealed severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. Research for CMV DNA Polymerase Chain Reaction (PCR) on urine, blood, cerebrospinal fluid, and nasopharyngeal secretions was positive.The mother had positive CMV IgG with negative IgM shortly before pregnancy. Serology for CMV was therefore not repeated during pregnancy, but CMV DNA performed on the Guthrie bloodspot taken at birth yielded a positive result, confirming the intrauterine transmission and congenital origin of the infection. The baby was discharged in good general condition and follow up showed a normal neurodevelopmental outcome at 9 months.
Conclusion
Although uncommon, congenital cytomegalovirus infection should be included in the differential diagnosis of intraventricular hemorrhage and cardiomyopathy. Furthermore, this case highlights the possible severity of congenital cytomegalovirus infection, even in cases of previous maternal immunity.
... Also, previous studies show that the possibility of "ping-pong" infections between infants and mothers exists, since infants often acquire CMV through breast milk, while mothers acquire infection after primary infection in their infants [12]. Another factor that allows reinfection is the immunodeficient status of the pregnant woman [13,14]. ...
Cytomegalovirus (CMV), a DNA virus that belongs to the Orthoherpesviridae family, infects 40–100% of people. Primary/non-primary CMV infection during pregnancy could cause fetal disabilities. After primary infection, CMV causes a latent infection and resides in cells of the myeloid compartment (CD34+, monocytes). Few studies have analyzed the impact of latent CMV infections on miscarriage history, pregnancy complications, and neonatal outcomes. Methods: Serum samples from 806 pregnant women (28.29 ± 4.50 years old) who came for a consultation at the Timisoara Clinical Emergency City Hospital between 2008 and 2010 were tested for anti-CMV IgM/IgG antibodies, and data about demography, obstetrical history, pregnancy complications, birth, and neonate were collected. The data were compared between the groups with and without latent CMV infection, and statistical significance was calculated. Results: We did not find a difference regarding cesarean section (OR = 0.916, p = 0.856), placental abruption (OR = 1.004, p = 1.00), pregnancy-induced hypertension rate (OR = 1.078, p = 1.00), secondary sex ratio (0.882, p = 0.857), APGAR score (p = 0.225), gestational age at birth (p = 0.434), or birth weight (p = 0.365). A borderline significant difference was found regarding the presence of miscarriage history: OR = 8.467, p = 0.051. Conclusions: The presence of latent CMV infection does not affect the likelihood of complications in healthy women. A borderline significantly higher prevalence of miscarriage history was found in women with latent CMV infection.
... Other authors have reported a much greater proportion of symptomatic cHCMV linked to reinfection during pregnancy [23,24]. Up to 10% of neonates with cHCMV infection are symptomatic and develop different sequelae. ...
Background
Human Cytomegalovirus (HCMV) is the most frequent congenital infection worldwide causing important sequelae. However, no vaccine or antiviral treatments are currently available, thus interventions are restricted to behavioral measures. The aim of this systematic review was to assess evidence from available intervention studies using hygiene-based measures to prevent HCMV infection during pregnancy.
Methods
Studies published from 1972 to 2023 were searched in Medline, PsycInfo, and Clinical Trials (PROSPERO, CRD42022344840) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality was assessed by two authors, using ROBE-2 and MINORS.
Results
After reviewing 6 selected articles, the outcome analysis suggested that implementation of hygiene-based interventions during pregnancy prevent, to some extent, the acquisition of congenital HCMV.
Conclusions
However, these conclusions are based on limited and low-quality evidence available from few studies using this type of intervention in clinical practice. Thus, it would be necessary to perform effective and homogeneous intervention studies using hygiene-based measures, evaluated in high-quality randomized controlled trials (RCTs).
... El tratamiento de la infección congénita por CMV es limitado, y las recomendaciones actuales en neonatos es el uso de ganciclovir vía intravenosa, por un periodo de seis semanas, con el objetivo de evitar o limitar las complicaciones neurológicas y auditivas que estos pacientes pueden presentar. En lactantes o niños mayores se puede utilizar valganciclovir vía oral teniendo resultados similares en la reducción de la carga viral al compararlo con ganciclovir 16 . En nuestro caso, el RN recibió terapia intravenosa con ganciclovir 12 mg/kg/día fraccionado en dos dosis cada 12 h, el tratamiento se inició desde el momento del diagnóstico, sin embargo, el efecto sobre la reducción de la carga viral no se pudo corroborar debido a la mala evolución clínica del paciente. ...
Blueberry muffin syndrome is characterized by an erythematousviolaceous maculopapular dermatosis due to extramedullary hematopoiesis. This entity has been associated with TORCH spectrum infections and noninfectious causes. We present the case of a preterm newborn, who since the prenatal control gave an ultrasound with data suggestive of congenital infection by cytomegalovirus (microcephaly, ventriculomegaly, intracerebral calcifications). On physical examination, he presented a violaceous macular dermatosis compatible with blueberry muffin syndrome. Cytomegalovirus viral load was detected in urine (81,200 copies/ml), with fatal outcome. Congenital cytomegalovirus infection should be considered in the presence of a blueberry muffin syndrome; an adequate diagnostic approach that includes maternal and perinatal history is essential, as well as serology studies for diseases of the TORCH spectrum in order to start early with treatment and avoid major comorbidities.
... HCMV reactivation from latency can be a major cause of human disease. For example, HCMV reactivation from latency in women is a common cause of congenital infection [3] and HCMV reactivation from latency can be found in up to 50 % of all solid organ transplant recipients and is a major factor in organ transplant rejection [4]. HCMV replication and reactivation from latency is also a major factor in the progression of AIDS [1,5]. ...
Antiviral therapy for human cytomegalovirus (HCMV) currently relies upon direct-acting antiviral drugs. However, it is now well known that these drugs have shortcomings, which limit their use. Here I review the identification and investigation of compounds targeting cellular proteins that have anti-HCMV activity and could supersede those anti-HCMV drugs currently in use. This includes discussion of drug repurposing, for example the use of artemisinin compounds, and discussion of new directions to identify compounds that target cellular factors in HCMV-infected cells, for example screening of kinase inhibitors. In addition, I highlight developing areas such as the use of machine learning and emphasize how interaction with fields outside virology will be critical for development of anti-HCMV compounds.
... On the other hand, seronegative pregnant women, once infected, will need time to develop antibodies, and this period is sufficient for the pathogenic agent to multiply and pass, via the placenta, to the fetus, causing severe damage [7]. Fetuses of healthy seropositive pregnant women are protected only partially since reinfections, infections by another strain or reactivations of latent infections may occur [8]. Despite the infection of the fetus in these cases, the impact on fetal development is not always severe [8,9]. ...
... Fetuses of healthy seropositive pregnant women are protected only partially since reinfections, infections by another strain or reactivations of latent infections may occur [8]. Despite the infection of the fetus in these cases, the impact on fetal development is not always severe [8,9]. Women with acquired or genetic immunodeficiency, or who are undergoing immunosuppressive therapy, might also be reinfected [10]. ...
Background:
Toxoplasma gondii (TG), a zoonotic protozoan parasite, belongs to a group of TORCH infectious agents, which can cause severe damage to the fetus if a primary infection occurs during pregnancy. After primary infection, TG rests lifelong in human organisms causing a latent infection. Most studies have analyzed the consequences of acute, but not latent, TG infection. This study analyzed the impact of latent toxoplasmosis on spontaneous abortion history, pregnancy complication rate and neonatal outcome.
Methods:
IgG and IgM anti-TG antibodies were tested in 806 pregnant women who were consulted at the Timisoara Clinical Emergency Hospital between 2008 and 2010. Demographic data, obstetrical history, and data about the pregnancy complications, birth and neonate were collected for each woman and comparisons between the groups, with and without latent TG infection, were made.
Results:
This study did not show differences between groups regarding the history of spontaneous abortion (OR = 1.288, p = 0.333), cesarean section (OR = 1.021, p = 0.884), placental abruption (OR 0.995, p = 0.266), pregnancy-induced hypertension rate (OR 1.083, p = 0.846), secondary sex ratio (1.043, p = 0.776), 1' APGAR score at birth (p = 0.544), gestational age at birth (p = 0.491) or birth weight (p = 0.257).
Conclusions:
The observed differences between the rate of pregnancy complications in the two groups of pregnant women with and without latent infection with TG, did not reach a statistical significance.
... Maternal non-primary CMV infections during pregnancy can cause both asymptomatic and symptomatic congenital CMV. However, in a much larger percentage of neonates than previously thought, congenital CMV with severe manifestations has been reported [13,16,20,50,60,[62][63][64][65][66]. Hadar et al. retrospectively investigated 107 neonates with congenital symptomatic CMV infections and demonstrated a statistically significantly low detection rate with regard to CMV-IgM antibodies when evaluating non-primary maternal infections occurring during pregnancy than that when evaluating primary infections (25% vs. 75.8%) ...
Cytomegalovirus (CMV) is the most common cause of intrauterine infection and serological assays are the primary tools for assessing CMV infections during pregnancy. CMV-specific immunoglobulin M (IgM) antibodies have been used as a diagnostic marker for primary CMV infection in pregnant women, although CMV-IgM has been detected in non-primary CMV infections. IgG avidity testing may aid the distinguishing of primary from non-primary CMV infection; however, there is no standardized assay for detecting this difference. Moreover, when maternal serology shows positive CMV-IgG with negative CMV-IgM findings, vertical transmission probability following primary CMV infection is often excluded. However, symptomatic congenital CMV infections in the context of negative findings for maternal CMV-IgM have been reported recently. The absence of CMV-IgM is recognized in both primary and non-primary CMV infections. Furthermore, maternal non-primary CMV infections during pregnancy may yield a greater proportion of symptomatic congenital CMV infections than previously thought. If universal prenatal screening is performed, ultrasonography for abnormal fetal findings should be conducted regardless of CMV-IgM antibody status. If not universally screened, CMV antibody screening should be performed whenever routine fetal ultrasound reveals abnormal findings. For suspected fetal CMV infection, amniotic fluid or postnatal infant urine CMV-DNA testing is required.
... Human cytomegalovirus (HCMV) is the most frequent congenital virus infection worldwide, with an incidence of approximately 0.64% live births (Mack et al. 2017;Rawlinson et al. 2017). Although congenital HCMV (cCMV) infection may involve many fetal organs, the most significant injuries are those related to lesions in the nervous system that are irreversible and persist for life (Fowler et al. 2003;Gabrielli et al. 2009;Kenneson and Cannon 2007;Zhang and Fang 2019). ...
Human cytomegalovirus (HCMV) causes congenital neurological lifelong disabilities. To date, the neuropathogenesis of brain injury related to congenital HCMV (cCMV) infection is poorly understood. This study evaluates the characteristics and pathogenetic mechanisms of encephalic damage in cCMV infection. Ten HCMV-infected human fetuses at 21 weeks of gestation were examined. Specifically, tissues from different brain areas were analyzed by: (i) immunohistochemistry (IHC) to detect HCMV-infected cell distribution, (ii) hematoxylin–eosin staining to evaluate histological damage and (iii) real-time PCR to quantify tissue viral load (HCMV-DNA). The differentiation stage of HCMV-infected neural/neuronal cells was assessed by double IHC to detect simultaneously HCMV-antigens and neural/neuronal markers: nestin (a marker of neural stem/progenitor cells), doublecortin (DCX, marker of cells committed to the neuronal lineage) and neuronal nuclei (NeuN, identifying mature neurons). HCMV-positive cells and viral DNA were found in the brain of 8/10 (80%) fetuses. For these cases, brain damage was classified as mild (n = 4, 50%), moderate (n = 3, 37.5%) and severe (n = 1, 12.5%) based on presence and frequency of pathological findings (necrosis, microglial nodules, microglial activation, astrocytosis, and vascular changes). The highest median HCMV-DNA level was found in the hippocampus (212 copies/5 ng of human DNA [hDNA], range: 10–7,505) as well as the highest mean HCMV-infected cell value (2.9 cells, range: 0–23), followed by that detected in subventricular zone (1.7 cells, range: 0–19). These findings suggested a preferential viral tropism for both neural stem/progenitor cells and neuronal committed cells, residing in these regions, confirmed by the expression of DCX and nestin in 94% and 63.3% of HCMV-positive cells, respectively. NeuN was not found among HCMV-positive cells and was nearly absent in the brain with severe damage, suggesting HCMV does not infect mature neurons and immature neural/neuronal cells do not differentiate into neurons. This could lead to known structural and functional brain defects from cCMV infection.
Graphical Abstract
... Human cytomegalovirus (HCMV) is the most frequent congenital virus infection worldwide, with an incidence of approximately 0.64% live births (Mack et al. 2017; Rawlinson et al. 2017). Although congenital HCMV (cCMV) infection may involve many fetal organs, the most signi cant injuries are those related to lesions in the nervous system that are irreversible and persist for life Fowler at al. 2003; Gabrielli et al. 2009; Kenneson and Cannon 2007). ...
Human cytomegalovirus (HCMV) causes congenital neurological lifelong disabilities. To date, the neuropathogenesis of brain injury related to congenital HCMV (cCMV) infection is poorly understood. This study evaluates the characteristics and pathogenetic mechanisms of encephalic damage in cCMV infection.
Ten HCMV-infected human fetuses at 21 weeks of gestation were examined. Specifically, tissues from different brain areas were analyzed by: i) immunohistochemistry (IHC) to detect HCMV-infected cell distribution, ii) hematoxylin-eosin staining to evaluate histological damage and iii) real-time PCR to quantify tissue viral load (HCMV-DNA). The differentiation stage of HCMV-infected neural/neuronal cells was assessed by double IHC to detect simultaneously HCMV-antigens and neural/neuronal markers: nestin (expressed in early differentiation stage), doublecortin (DCX, identifying neural cells with determined lineage) and neuronal nuclei (NeuN, identifying mature neurons).
HCMV-positive cells and viral DNA were found in the brain of 8/10 (80%) fetuses. For these cases, brain damage was classified as mild (n=4, 50%), moderate (n=3, 37.5%) and severe (n=1, 12.5%) based on presence and frequency of pathological findings (necrosis, microglial nodules, microglial activation, astrocytosis and vascular changes). The highest median HCMV-DNA level was found in the hippocampus (212 copies/5ng of humanDNA [hDNA], range: 10-7,505) as well as the highest mean HCMV-infected cell value (2.9 cells, range: 0-23), followed by that detected in subventricular zone (1.8 cells, range: 0-19). This suggested a preferential viral tropism for neural stem/progenitor cells (NSPCs), residing in these regions, confirmed by the expression of DCX and nestin in 94% and 63.3% of HCMV-positive cells, respectively. NeuN was not found among HCMV-positive cells and was nearly absent in the brain with severe damage, suggesting HCMV does not infect mature neurons and NSPCs do not differentiate into neurons. This could lead to known structural and functional brain defects from cCMV infection.
