Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection

Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection

Cytomegalovirus infection and gastric emptying

Gastrointestinal infection due to cytomegalovirus occurs frequently in liver transplant recipients. Upper gastrointestinal cytomegalovirus infection is associated with subjective complaints of nausea, a sense of abdominal fullness, and occasionally emesis and/or dysphagia. In order to determine whether these symptoms reflect a disruption of the normal motility of the stomach, the following study was performed. Eleven individuals who were evaluated for liver transplantation were prospectively recruited and studied as follows: (1) upper gastrointestinal endoscopy with biopsy of the gastric antral mucosa; (2) viral culture of the gastric mucosa; (3) a histologic examination of the gastric mucosa; and (4) a radionuclide gastric emptying study was obtained before and 4—8 weeks following successful liver transplantation. Prior to liver transplantation, none had symptoms of nausea, vomiting, or epigastric fullness. All were culture-negative for cytomegalovirus. All had endoscopic and histologic evidence of portal hypertensive gastro-pathy but none had antral erosions or ulcers. All demonstrated normal gastric emptying of a liquid meal. Following liver transplantation, 6 remained free of gastric cytomegalovirus while 5 developed a culture-confirmed gastric cytomegalovirus infection. Those that developed a gastric cytomegalovirus infection also had more gastric symptoms, and more gastric histologic abnormalities. Moreover, those with a gastric cytomegalovirus infection demonstrated enhanced gastric retention of a liquid meal (P<0.01). © 1992 by Williams & Wilkins

Acquired Cytomegalovirus Infection in an Extremely Low-Birth Weight Infant Presenting with a Severe Sepsis-Like Syndrome

Cytomegalovirus infection is one of the most common congenital infections worldwide. Moreover, it seems to be an important cause of postnatally acquired infection. Perinatal transmission can occur intrapartum (from the birth canal), from a blood transfusion, via maternal breast milk, or from close contact with infected people. The risk of breast milk-acquired cytomegalovirus infection is higher in countries with a high prevalence of cytomegalovirus immunoglobulin G-positive women. Usually, acquired cytomegalovirus infection is asymptomatic, especially in term infants. However, preterm infants can present with a sepsis-like syndrome and multiple organ involvement. A high index of suspicion is required to make an early diagnosis. Therapeutic guidelines for symptomatic postnatal cytomegalovirus infection are not yet available. More studies are required to understand the long-term sequelae of postnatally acquired cytomegalovirus infection and know which is the best strategy to avoid cytomegalovirus post-natal transmission.info:eu-repo/semantics/publishedVersio

Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts.

Maternal primary and non-primary cytomegalovirus (CMV) infection during pregnancy can result in in utero transmission to the developing fetus. Congenital CMV (cCMV) can result in significant morbidity, mortality or long-term sequelae, including sensorineural hearing loss, the most common sequela. As a leading cause of congenital infections worldwide, cCMV infection meets many of the criteria for screening. However, currently there are no universal programs that offer maternal or neonatal screening to identify infected mothers and infants, no vaccines to prevent infection, and no efficacious and safe therapies available for the treatment of maternal or fetal CMV infection. Data has shown that there are several maternal and neonatal screening strategies, and diagnostic methodologies, that allow the identification of those at risk of developing sequelae and adequately detect cCMV. Nevertheless, many questions remain unanswered in this field. Well-designed clinical trials to address several facets of CMV treatment (in pregnant women, CMV-infected fetuses and both symptomatic and asymptomatic neonates and children) are required. Prevention (vaccines), biology and transmission factors associated with non-primary CMV, and the cost-effectiveness of universal screening, all demand further exploration to fully realize the ultimate goal of preventing cCMV. In the meantime, prevention of primary infection during pregnancy should be championed to all by means of hygiene education

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Neutralizing Monoclonal Antibodies Reduce Human Cytomegalovirus Infection and Spread in Developing Placentas.

Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects worldwide, yet the most effective strategies for preventing virus transmission during pregnancy are unknown. We measured the efficacy of human monoclonal antibodies (mAbs) to HCMV attachment/entry factors glycoprotein B (gB) and the pentameric complex, gH/gL-pUL128-131, in preventing infection and spread of a clinical strain in primary placental cells and explants of developing anchoring villi. A total of 109 explants from five first-trimester placentas were cultured, and infection was analyzed in over 400 cell columns containing ~120,000 cytotrophoblasts (CTBs). mAbs to gB and gH/gL, 3-25 and 3-16, respectively, neutralized infection in stromal fibroblasts and trophoblast progenitor cells. mAbs to pUL128-131 of the pentameric complex, 1-103 and 2-18, neutralized infection of amniotic epithelial cells better than mAbs 3-25 and 3-16 and hyperimmune globulin. Select mAbs neutralized infection of cell column CTBs, with mAb 2-18 most effective, followed by mAb 3-25. Treatment of anchoring villi with mAbs postinfection reduced spread in CTBs and impaired formation of virion assembly compartments, with mAb 2-18 achieving better suppression at lower concentrations. These results predict that antibodies generated by HCMV vaccines or used for passive immunization have the potential to reduce transplacental transmission and congenital disease

Using the nonhuman primate model of HCMV to guide vaccine development.

The natural history of human cytomegalovirus (HCMV) is inextricably associated with mucosal surfaces. The vast preponderance of primary infections occur following mucosal exposure to infectious virions, and the high seroprevalence of HCMV throughout the world is due to long-term excretion of HCMV in bodily fluids from multiple mucosal sites. Accumulating evidence presents a model where the earliest virus-host interactions following infection dictate the long-term pattern of infection, alter innate immune responses that skew adaptive responses to enable persistence within an immune host, and are essential for reinfection of a host with prior immunity. HCMV has evolved a complex repertoire of viral functions fine-tuned to manipulate the immune environment both locally at the sites of infection and systemically within an infected host. Collectively, viral immune modulation represents a significant impediment for an HCMV vaccine. As HCMV can disseminate beyond mucosal surfaces to reinfect immune hosts, it may not matter whether prior immunity results from prior infection or immunization. A better understanding of the earliest virus-hosts interactions at mucosal surfaces may identify elements of the viral proteome that are especially susceptible to vaccine-mediated disruption and prevent challenge virus from disseminating to distal sites, particularly the maternal-fetal interface

Cytomegalovirus infection of the upper gastrointestinal tract following liver transplantation—incidence, location, and severity in cyclosporine- and FK506-treated patients

One hundred and forty randomly selected liver transplant recipients were studied before and after primary orthotopic liver transplantation for the presence or absence of CMV enteritis. Following OLTx, 65 patients were treated with cyclosporine A and 75 were treated with FK506. The two groups were similar with regard to the incidence, location, and outcome of their upper gastrointestinal CMV infection. Prior to OLTx, only one patient had evidence of enteric CMV infection. The incidence of CMV enteritis post-OLTx was 27.7% in the CsA-treated group and 20% in the FK-treated group. During the first posttransplant month, no patient in the FK-treated group developed CMV enteritis, compared with 11.5% of the patients who were treated with CsA (P<0.05). Gastric CMV was found in over 80% of those positive for any organ in either group. In addition to CMV infection of the upper gastrointestinal tract, clinically evident CMV disease involved more nonenteric organs in the CsA-treated group than in the FK-treated group. In the CsA-treated group, CMV-negative patients had a statistically higher 1-year survival rate (100%) than CMV-positive patients (77.8%) (P<0.05). In the FK-treated group, no difference in survival was observed between CMV-positive or CMV-negative cases at 1 year. Of the patients on CsA, 20% received OKT3 for persistent rejection, as compared with 13% in the FK-treated group. The patients receiving both CsA and OKT3 had a higher rate of upper gastrointestinal CMV infection than did FK-treated patients who also received OKT3 therapy (38.5% versus 20%, respectively). Based upon these data, it can be concluded that (1) patients receiving FK have a lower incidence of enteric CMV infection; (2) following OLTx, upper gastrointestinal CMV infection presents later in FK-treated patients; (3) the stomach is the most frequently involved organ in the UGIT; (4) FK-treated liver recipients have less severe enteric CMV infection than do CsA-treated patients; (5) enteric CMV is not a major cause of mortality in liver trans lant recipients; and (6) in patients receiving FK, those who require OKT3 therapy do not appear to be at a greater risk for the development of CMV enteritis than those who do not. © 1992 by Williams & Wilkins

Episodic vestibular symptoms in children with a congenital cytomegalovirus infection

Objective: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss in children. Although cCMV-induced vestibular loss is demonstrated in several studies, the occurrence of vertigo has been described in only two cases to date. The aim of this paper is to discuss the underlying pathophysiology of recurrent vestibular symptoms in children with cCMV, based on five cases investigated in our center and an extensive research of the literature. Study design: Retrospective case series. Setting: Tertiary referral center. Patients: This case series describes five pediatric cCMV-patients (three boys, two girls). Four of them were symptomatic at birth, one was asymptomatic. Three patients underwent cochlear implantation. The age of onset of the vestibular symptoms varied from 2;0 to 7;3 years of age. Intervention: None. Main outcome measures: Details regarding the patient history and results of cranial imaging, audiological, vestibular, and neurological assessments were collected retrospectively. Results: The selected cases suffered from recurrent vestibular symptoms. All patients had delayed onset, fluctuating, and/or progressive hearing loss. In all cases, the attacks were accompanied with nausea and vomiting and occurred without clear-cut trigger. Migraine and epilepsy often were proposed as first diagnosis, although they could not be confirmed eventually. Four out of five patients were diagnosed with a peripheral vestibular deficit. Conclusions: Diagnosis of vestibular symptoms in children with cCMV is complex, given the multiple morbidities than can occur. Peripheral vestibular causes should be considered in the diagnosis, as important vestibular deficits are demonstrated in this population

Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes

We have established a murine model system for exploring the ability of a CD4 subset-deficient host to cope with cytomegalovirus infection, and reported three findings. First, an antiviral response of the CD8 subset of T lymphocytes could be not only initiated but also maintained for a long period of time despite a continued absence of the CD4 subset, whereas the production of antiviral antibody proved strictly dependent upon help provided by the CD4 subset. Second, no function in the defense against infection could be ascribed as yet to CD4-CD8- T lymphocytes, which were seen to accumulate to a new subset as a result of depletion of the CD4 subset. This newly arising subset did not substitute for CD4+ T lymphocytes in providing help to B lymphocytes, and was also not effective in controlling the spread of virus in host tissues. As long as a function of these cells in the generation and maintenance of a CD8 subset-mediated response is not disproved, caution is indicated with concern to an autonomy of the CD8 subset. Third, even though with delay, the CD8+ effector cells raised in the CD4 subset- deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue