Generalized Cytomegalovirus Infection Research Articles

Challenging problems of congenital cytomegalovirus infection therapy: case study

Cytomegalovirus infection is the most common congenital infection, causing development disorders of the fetus’ nervous system. The article describes two clinical cases of congenital cytomegalovirus infection, which highlight the crucial importance of an early administration of direct antiviral drugs (ganciclovir, valgancyclovir) for the generalized manifest forms of infection. The first clinical case study (a girl, most likely infected at the beginning of the second trimester of pregnancy) deals with the development of the classic triad of severe congenital CMV infection (small weight for gestational age, direct hyperbilirubinemia and petechial rash). Given that the intrauterine developmental anomalies specific for CMV were detected in the fetus on the 32nd week of pregnancy during her mother’s comprehensive test examination, the treatment of the infant girl with ganciclovir could have started immediately after her birth. The second clinical case study describes a congenital generalized cytomegalovirus infection in a child with malformations of internal organs and the central nervous system. The described two clinical cases of congenital cytomegalovirus infection highlight the crucial importance of ganciclovir and point to the fact that the isolated use of hyperimmune immunoglobulin does not stop the progression of the disease. The chance of a favorable outcome of the disease is much higher if the clinical diagnosis is established as early as possible after the birth of the child and etiotropic therapy is fully administered.

В12-дефицитная анемия в сочетании с активной цитомегаловирусной инфекцией у ребенка одного года

The article presents a clinical case of B12-deficiency anemia in combination with active cytomegalovirus infection in a one-year-old child. This type of anemia is extremely rare in childhood, under certain circumstances, including the enthusiasm for restrictive diets among young patients’ mothers. In the described case, severe megaloblastic macrocytic anemia was combined with generalized cytomegalovirus infection, which aggravated the course and prognosis of the disease. These pathologies led to damage of the central nervous system with a tempo neurological deficit, as well as the development of protein-energy insufficiency. Complex therapy included hemotransfusion of erythrocyte mass, injections of anticytomegalovirus immunoglobulin and cyanocobalamin. The general condition of the child improved, recovery of previously lost skills and significant positive laboratory dynamics were noted after the therapy.

Маркеры патологического течения перинатального периода у детей с гиперэхогенным внутрисердечным фокусом

Aim: to describe the course of perinatal period in children with echogenic intracardiac focus (EIF) diagnosed in the antenatal period.Patients and Methods: in this case-control study, the groups were similar in age, obstetric history, and somatic status of mothers. Group 1 included 214 pregnant women whose fetus (newborn later) was diagnosed with EIF. Inclusion criteria were an echoic focus within the fetal heart (by prenatal ultrasound) as well as pregnancy follow-up and childbirth in the Perinatal Center of Tyumen city. Group 2 included 107 pregnant women whose fetus (newborn later) had no this sonographic sign. Retrospective analysis of the course of antenatal and intranatal periods of newborns with EIF was performed. The course of early neonatal period was described. Placental histology (n = 69) and autopsies of perinatal losses (n=12) were discussed.Results: it was demonstrated that EIFs identified for the first time after 20 weeks of gestation persist after delivery much more common (p<0.01) when associated with impaired fetoplacental circulation. More than 50% of mothers (p>0.01) whose fetuses were diagnosed with EIF had patho-logical pregnancy. During the delivery, clinical signs of chronic hypoxia in newborns with EIF were identified twice as common as in newborns without EIF (p=0.029). Moreover, none of the children had typical signs of Down syndrome while the number of preterm newborns was simi-lar (p>0.05). Only newborns with EIF were diagnosed with different types of birth defects (7.94%) and generalized cytomegalovirus infection (1.46%). Hypoxic cardiopathy (that illustrates cardiovascular deadaptation) was 3.2 times more common in newborns with EIF (p=0.005) Conclusion: combination of EIF (2.67±0.9 mm) localized in the left or right ventricle and other sonographic signs, central nervous system defects and/or cardiovascular abnormalities require screening for perinatal infections as well as uterine and umbilical artery Doppler to minimize the risk of perinatal events.Keywords: perinatal period, echogenic intracardiac focus, newborns, perinatal losses, congenital anomaly, hypoxic cardiopathy, sonographic sign.For citation: Malinina E.I., Rychkova O.A., Chernysheva T.V. Markers of the pathological course of perinatal period in children with echogenic intracardiac focus. Russian Journal of Woman and Child Health. 2020;3(2):132–135. DOI: 10.32364/2618-8430-2020-3-2-132-135.

THE METHOD OF TREATMENT OF GENERALIZED CYTOMEGALOVIRUS INFECTION IN INFANTS

Purpose of the study. Evaluation of the effectiveness of treatment of generalized cytomegalovirus infection (CMVI) in infants with a combination of ganciclovir and VIFERON®. Materials and methods. 52 children of the first months of life were treated with generalized CMV. Patients are divided into 3 groups: the first included 25 children who received ganciclovir for 14—21 days, then — IFN-α-2b in combination with antioxidants vitamins E and C (VIFERON®); The second group consisted of 17 patients receiving only ganciclovir; in the third group included 10 children who had only symptomatic treatment of CMVI: hepatoprotectors, broad-spectrum antibiotics (ceftriaxone, ampicillins) at age dosages. Therapy was carried out under the control of viral load in the blood serum on the 14th and 21st day from the start of treatment. Patients of the 1st group with a decrease in the clinical manifestations of CMV and a decrease in the viral load to 104—103 copies/ml on the 14—21 day were prescribed rectal suppositories of IFN-α-2b (VIFERON®) 150 000 IU according to the original scheme. Results. In the 1st group, all children during 3—6 months had an elimination of the virus from the blood and liquor. Relapse of CMV was not observed. Children of the second group had a decrease in the viral load was observed, but the elimination of the virus from the blood, the cerebrospinal fluid did not occur. Patients of the 3rd group had the viral load remained at the same level, it increased by 102 copies/ml at one patient. The conclusion. Using of combined antiviral therapy with ganciclovir and IFN-α-2b in combination with antioxidants vitamins E and C (VIFERON®) promotes elimination of the virus from blood and liquor, transferring and keeping it in an inactive state, which prevents the development of complications. The proposed method for treatment of CMV can be successfully used in inpatient and outpatient settings.

Potential Contribution of Cytomegalovirus Infection to Prenatal and Early Neonatal Mortality of Monkeys in the Adler Breeding Center

Scrapings from the cervical canals and uterine cavities of females with a history of miscarriages, pathological deliveries, and stillbirths were tested for the cytomegalovirus DNA. The incidence of the agent in the females with a history of gestosis and abnormal deliveries was significantly higher than in females without anamnesis of this kind. Parenchymatous organs of stillborn neonates and animals dead during the first month of life were studied. This analysis and studies of the umbilical cords and placentas showed generalized cytomegalovirus infection in 22% dead animals, which objectively proved intrauterine infection.

Debilitating chronic diarrhea caused by generalized gastrointestinal cytomegalovirus infection in an immunocompetent adult.

Gastrointestinal cytomegalovirus (CMV) infection is a common opportunistic infection in immunocompromised patients, especially patients with acquired immunodeficiency syndrome and transplant recipients. In contrast, CMV infection of the gastrointestinal tract is rare in immunocompetent individuals. We report a case of severe, protracted, and debilitating diarrhea caused by generalized CMV infection of the gastrointestinal tract in an elderly woman with no apparent immunosuppression. An extensive diagnostic investigation demonstrated CMV-associated disease affecting both the upper and lower gastrointestinal tracts (esophagus, small intestine, and colon). Such extensive simultaneous involvement of the alimentary tract in an immunocompetent patient is rare and presents a diagnostic and therapeutic challenge. The diagnosis was based on a combination of endoscopic, histopathological, serological, and polymerase chain reaction analysis findings and our patient was successfully treated with intravenous ganciclovir. Our case demonstrates that gastrointestinal CMV infection should be considered in the differential diagnosis of severe chronic diarrhea in immunocompetent patients and that antiviral treatment may be justified in this setting.

Cytomegalovirus‐induced cutaneous microangiopathy manifesting as lower limb ischemia in a human immunodeficiency virus‐infected patient

Cutaneous infections by cytomegalovirus (CMV) are rare and often difficult to diagnose both clinically and histopathologically. A wide range of different clinical manifestations have been described in the literature, especially in immunosuppressed patients. CMV-induced thrombosis has also been reported in these patients, and various mechanisms have been proposed to explain the role of CMV in the thrombotic process, including direct damage of the endothelial cells, activation of coagulation factors and inducing the production of antiphospholipid antibodies. We present the case of a human immunodeficiency virus (HIV)-infected woman who developed distal ischemic lesions of the lower extremities during a generalized CMV infection. We discuss the role of CMV and antiphospholipid antibodies in the pathogenesis of thrombosis in immunosuppressed patients.

Diagnostic problems of cytomegalovirus infections in premature newborns

Abstract Introduction Cytomegaly is an infectious, widespread viral disease. It is caused by Cytomegalovirus (CMV), which belongs to the DNA viruses group from the Herpesviridae family. The virus is human specific. Once infected, a person remains seropositive to the end of life and the virus remains latent particularly in leukocytes, which are its main reservoir. Many different disease manifestations, which depend partially on a patient's age, but mostly on an immunological state, may be caused by CMV. Aim The aim of this work was the assessment and histoclinical analysis of CMV infection in a male newborn with a congenital anomaly syndrome. Case study and examination results A male newborn, born in the 30th week of gestation, diagnosed with congenital anomaly syndrome, Apgar score was 2. In the neonatal period hypertrophic cardiomyopathy involving the right ventricle, esophageal atresion, esophagotracheal fistula, hepatosplenomegaly, respiratory insufficiency and hyperechogenic periventricular structures in the brain were diagnosed. During the entire hospitalization period a progression of inflammatory changes in the lungs was observed. The results of serological tests to detect anti-CMV and toxoplasmosis specific antibodies were: CMV–IgG 21.00 IU/mL; CMV–IgM negative; Toxo–IgG 4.0 IU/mL; Toxo–IgM negative. Restoration of esophageal continuity and repair of the fistula were performed surgically. Follow-up serological test was positive for anti- CMV antibodies in the IgG and IgM classes. The patient died on the 79th day following hospital admission. Autopsy and histopathological tests confirmed generalized cytomegalovirus infection. Discussion Most advanced histopathological changes were observed in lungs, liver, spleen and brain. Characteristically changed cells, confirming generalized cytomegalovirus infection were found in all the aforementioned organs. Conclusions . CMV infections, particularly congenital infections in premature newborns are challenging diagnostic and therapeutic problems. Routine diagnostic procedures to detect CMV infections seem to be necessary in risk groups, particularly for premature infants. Negative anti-CMV antibodies result in patients with an insufficient immune system, does not exclude the presence of this infection. Early diagnosis and treatment of congenital cytomegaly may positively affect a patient's clinical condition and prolonged prognosis.

Free allogeneic muscle transfer for cranial reconstruction

An allogeneic muscle transfer was used to cover a large cranial defect in one of a pair of craniopagus twin separated a decade ago. Both separated twins died, 7 months apart, with the twin that had received the transfer dying first. The cause of death was generalised cytomegalovirus infection. An autopsy showed extensive brain necrosis caused by vascular insufficiency, a result of the abnormal vascular anatomy at birth. The muscle allograft showed no signs of rejection. Progress in immunosuppressive treatment over the last decade, which has enabled successful allogeneic nerve grafts and composite-tissue transplantations, might make muscle transplantation for the coverage of large defects, with and without functional demands, feasible in the future.

Detection of the human cytomegalovirus gene in placental chronic villitis by polymerase chain reaction

Placental chronic villitis was observed in 44 cases (2.12%) of 2,073 histologically examined placentas. Infiltrating lymphocytes in chronic villitis were determined by immunohistochemistry to be predominantly helper/inducer T cells. Detection of the cytomegalovirus (CMV) gene was performed on paraffin-embedded sections by polymerase chain reaction (PCR) using two different primers (CMV immediate early gene and CMV late antigen gp 64). Both CMV immediate early gene and late antigen gp 64 gene were detected in one case. Cytomegalovirus late antigen gp 64 gene was observed in only three cases. Among these four cases, the cytomegalic inclusion body was observed only in a single case with light microscopic examination. In two cases generalized CMV infection was manifested during the early infantile period and the patient died of the disease. The other two cases were asymptomatic. Our data suggest that approximately 9% of the cases of chronic villitis are caused by CMV infection, and most of them are difficult to detect morphologically. Detection of CMV gene by PCR using primers, especially late antigen gp 64 gene, is very useful for assessing the cause of placental chronic villitis.

Combined hepatic and renal transplantation in primary hyperoxaluria type I: Clinical report of nine cases

The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ. One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education. A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

Combined hepatic and renal transplantation in primary hyperoxaluria type I: clinical report of nine cases

purpose and patients and methods: The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ. results: One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education. conclusions: A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

Systemic Cytomegalovirus in a Patient with the Keratitis, Ichthyosis, and Deafness (KID) Syndrome

We describe a patient with the keratitis, ichthyosis, and deafness (KID) syndrome who also had a generalized cytomegalovirus infection. Patients with the KID syndrome are susceptible to not only bacterial and fungal infections, but also to viral infections.

Experimental activation of latent cytomegalovirus infection of the captive bred (F1) cynomolgus monkeys by live or killed varicella-zoster virus inoculated under immunosuppression.

F1 cynomolgus monkeys bred in captivity and thought to be "SPF" had latent cytomegalovirus (CMV) infection although less frequently than in wild-born monkeys. Latent CMV could be activated under severe immunosuppression by inoculation with a certain strain of varicella-zoster virus (VZV) as shown in a previous study. We carried out further experiments using live and formalin-inactivated VZV in F1 monkeys which were sero-positive for CMV, but not for any other viruses. The results showed that both live and inactivated VZV were equivalent in permitting activation of latent CMV, suggesting that the VZV inoculum merely played an immunogenic, but not any virological, role in this case. Captive F1 monkeys, however, carried fewer CMV, and/or resisted CMV reactivation more than the wild monkeys in the previous studies, judging from the time required for generalized CMV infection to become expressed.

A Chronic Type of Adult T-Cell Leukemia Accompanied by Generalized Cytomegalovirus Infection

A Chronic Type of Adult T-Cell Leukemia Accompanied by Generalized Cytomegalovirus Infection

In situ hybridization analysis of cytomegalovirus lytic infection in Kaposi's sarcoma associated with AIDS. A study of 14 autopsy cases.

Cytomegalovirus (CMV) was assayed by in situ hybridization with commercially available biotin-labeled CMV-DNA probes in 45 formalin-fixed paraffin-embedded autopsy specimens with Kaposi's sarcoma from 14 cases of the acquired immune deficiency syndrome (AIDS). In seven of the 14 cases, a few scattered hybridizing cells were detected in Kaposi's sarcoma, but not all specimens from the same case showed such cells. Most of the positive cells were peculiarly swollen and not typical of Kaposi's sarcoma cells. All positive cases had at least some CMV-infected organs with typical cytomegalic cells containing nuclear inclusions while five of the 7 negative cases revealed no CMV-infected tissue by conventional light microscopy. Our results suggest that this in situ hybridization procedure using biotin-labeled DNA probes only reveals generalized CMV infection that is a consequence of impairment of immune mechanisms in AIDS patients.

Primary Hyperoxaluria (Type I): Attempted Treatment by Combined Hepatic and Renal Transplantation

A case is reported of a patient with renal failure and developing systemic and renal oxalosis due to pyridoxine-resistant type I primary hyperoxaluria. In spite of vigorous haemodialysis and hydration before and after operation, an allografted cadaveric kidney failed because of oxalate deposits in the transplant. The patient was treated by combined hepatic and renal transplantation. The liver allograft functioned well but the kidney had poor function due to primary acute tubular necrosis aggravated by steroid-associated acute pancreatitis, systemic cytomegalovirus infection and high cyclosporin A levels. The patient died from generalised cytomegalovirus infection. The early course after operation was associated with a reduced rate of oxalate production, which would slow the rate of oxalate deposition in the tissues. The size of the oxalate metabolic pool was also diminished. These observations are compatible with the grafted liver having corrected the metabolic lesion.

Transmission of maternal cytomegalovirus-specific immunity in the guinea pig

The prenatal and perinatal transmission of maternal cytomegalovirus (CMV)-specific immunity was studied in the guinea pig by cross-fostering newborns of seropositive and seronegative mothers. Resistance to CMV was assessed by challenging the newborn and adult offspring with sublethal doses of CMV and following the course of their acute CMV disease. Newborns were found to acquire detectable CMV antibody via the placental route but not the breast milk route. When compared to neonates with no acquisition of CMV immunity, neonatal offspring born to or foster fed on seropositive mothers were protected against generalized CMV infection to various degrees. The immunity transferred by pregnant mothers that had seroconverted prior to pregnancy was short lived and was more protective in newborns with detectable CMV antibody. Mothers that experienced primary CMV infection during pregnancy conferred on their progeny the most significant and long-lasting resistance against CMV challenge. This study demonstrates that newborn guinea pigs may acquire CMV-specific immunity from seropositive mothers; the degree of protection against CMV infection depends on the route of acquisition of immunity and on the time of maternal seroconversion.

Vaccination against transplacental cytomegalovirus transmission: vaccine reactivation and efficacy in guinea pigs.

The guinea-pig model of cytomegalovirus (CMV) infection was used in continuing studies of experimental CMV vaccines for prevention of congenital CMV infection. Low-passage guinea-pig cytomegalovirus (GPCMV) vaccine, which has been shown to be effective in preventing transplacental CMV transmission, was tested for reactivation during pregnancy. In Hartley strain guinea pigs intraperitoneally given 10(5.5) 50% tissue culture infective doses (TCID50) of low-passage vaccine, 27 (41%) of 66 throat swabs obtained during subsequent pregnancies showed CMV, in contrast to 28 (24%) of 115 throat swabs obtained from nonpregnant control animals. High-passage GPCMV vaccine (approximately 5 X 10(3) TCID50) did not cause acute viremia, detectable generalized infection, or GPCMV reactivation during subsequent pregnancies. Immune pregnant animals and their fetuses were protected against generalized CMV infection when challenged with virulent GPCMV. In contrast, nonimmune pregnant controls developed generalized maternal, placental, and fetal infection. Experimental low-dose, high-passage GPCMV vaccine can protect against transplacental CMV transmission without apparent vaccine reactivation during pregnancy.

A Case of Adult T-cell Leukemia with Generalized Cytomegalovirus Infection, Pneumocystis Carinii Pneumonia and Hypoimmunoglobulinemia

A Case of Adult T-cell Leukemia with Generalized Cytomegalovirus Infection, Pneumocystis Carinii Pneumonia and Hypoimmunoglobulinemia