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Biomedical subjects

Tiziana Lazzarotto

Publications and source records attributed to Tiziana Lazzarotto.

17 recordsLinked to original sources

H5N1 Clade 2.3.4.4b Infections in Domestic Cats During an Avian Influenza Outbreak in Italy: Implications for One Health Surveillance.

BACKGROUND: H5Nx goose/Guangdong (Gs/GD) lineage highly pathogenic avian influenza (HPAI) viruses pose a significant public health threat due to their global spread, mutation accumulation, and expanding host range. The descendant clade 2.3.4.4b has been causing widespread infections in birds and increasing spillover events in mammals. METHODS: This report documents the first fatal case of highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b infection in a domestic cat in Italy, detected in early January 2025. The cat (CAT 1) resided on a backyard poultry farm experiencing a high pathogenicity avian influenza outbreak and succumbed rapidly following the onset of respiratory signs. A second exposed cat (CAT 2) developed clinical disease without fatal outcome. Comprehensive outbreak investigations were conducted, including pathological, serological, molecular analyses, and genomic characterization. RESULTS: Pathological examination of CAT 1 revealed acute necrotizing bronchointerstitial pneumonia, non-suppurative meningoencephalitis, and disseminated foci of hepatic necrosis. Interestingly, the PB2-E627K mutation associated with mammalian virus adaptation was observed in the feline viral isolate compared to avian isolates. Such polymerase complex mutations are key determinants of host range and increase pathogenicity in mammals. CAT 2 from the same farm tested negative for AIV genome detection but subsequently seroconverted for antibodies against NPA, H5, and N1. CONCLUSION: Sharing these findings is crucial for surveillance aimed at enabling early identification of increased risks to human and animal health, preventing cross-species viral transmission and mitigating the risk of potential spillover events.

Animals↗

Autochthonous chikungunya virus (CHIKV) outbreak in the province of Modena, Emilia-Romagna region, Italy, August to October 2025: epidemiology, clinical features and virological findings.

Between 10 August and 31 October 2025, 343 cases (306 confirmed and 37 probable) of symptomatic autochthonous chikungunya virus (CHIKV) infection were notified in eight municipalities in the province of Modena, Emilia-Romagna region, northern Italy. The infection was diagnosed by detection of CHIKV RNA in blood and urine samples, and by detection of IgM antibodies against CHIKV. Most common symptoms were arthralgia (n = 326) and fever (n = 317). No fatalities were reported. Chikungunya virus RNA was detected in 39 (14.8%) of 263 pools of Aedes albopictus mosquitoes, thereby confirming local vector-borne transmission. Sequences from 11 case samples and two mosquito pools were whole genome sequenced. The viral strain belonged to the East/Central/South African (ECSA) lineage 2 and was closely related to the strains circulating in Reunion Island in 2024-25. The public health response included rapid vector control measures, reinforced epidemiological surveillance and multidisciplinary coordination between public health authorities and clinicians, laboratories and entomologists. This was one of the largest autochthonous CHIKV outbreaks ever recorded in a temperate European region. It highlights the critical importance of integrated, multidisciplinary preparedness and response for arboviral threats in non-endemic areas.

Humans↗

Cytomegalovirus (CMV)-encoded UL144 (truncated tumor necrosis factor receptor) and outcome of congenital CMV infection.

BACKGROUND: Cytomegalovirus (CMV) is the most common congenital infection in humans. The effect of viral strains on the outcome of congenital CMV is debated. We evaluated whether UL144 polymorphisms in amniotic fluid from CMV-infected Italian women were associated with terminations of pregnancy, subsequent disease in their offspring, or viral load. METHODS: The study was nested within a prenatal CMV program. We sequenced the UL144 gene from 66 amniotic-fluid samples, without knowledge of pregnancy outcome. We performed data analyses on 56 samples for which all information was available. RESULTS: Genotype C was associated with termination of pregnancy (P=.03). Genotype B was associated with fewer terminations of pregnancy (P=.003). A possible association was found between genotype C and symptomatic disease in newborns (odds ratio, 8.81 [95% confidence interval, 0.48-164.02]; P=.05). There was no association between specific genotype and the viral load in amniotic fluid. Symptomatic newborns who had the most common UL144 genotype (B) were more likely to have higher viral loads than were asymptomatic infants (P=.003). CONCLUSIONS: UL144 polymorphisms may be associated with the outcome of congenital CMV infection. Larger studies should be conducted to confirm this association, before genotype analysis can be used, along with other factors, in considering terminations of pregnancy.

Amniotic Fluid↗

Pregnancy outcome after early detection of bacterial vaginosis.

OBJECTIVE: To assess if detecting bacterial vaginosis either in early pregnancy or at midtrimester may predict adverse pregnancy outcome in women at risk for preterm delivery. STUDY DESIGN: 242 pregnant women with a previous preterm delivery were evaluated for bacterial vaginosis either in the first trimester (prior to 10+0 weeks) or in the second one (24-26 weeks). Adverse outcome was intended as miscarriage (< or =25 weeks), or premature delivery (< or =36+6). RESULTS: The risk of adverse pregnancy outcome was significantly increased in women diagnosed at first trimester with bacterial vaginosis (OR: 4.56; 95% CI: 2.54-8.93); the same finding at midtrimester did not increase significantly the risk of preterm delivery. CONCLUSIONS: Early screening for bacterial vaginosis in pregnant women who experienced a preterm delivery may help in predicting the risk of adverse outcome.

Abortion, Spontaneous↗

Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected newborns.

OBJECTIVE: Human cytomegalovirus (CMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection in developed countries leading to psychomotor impairment and deafness. Diagnostic techniques for CMV detection have greatly improved during recent years with the advent of sophisticated serological and virological methods. The aim of the present study was to assess the diagnostic and prognostic value of detection and quantification of virus in neonatal blood samples of symptomatic and asymptomatic newborns with CMV congenital infection. METHODS: Between January 1997 and December 2003, we studied 99 newborns who were born to women with primary, recurrent, and undefined CMV infection during pregnancy. CMV congenital infection was identified by isolation of the virus in urine within the second week of life. Fifty-eight of 99 infants were infected and were assessed clinically for disease in the newborn period and classified as having symptomatic or asymptomatic infection on the basis of physical, instrumental, and laboratory findings. The infants were followed up from birth according to a protocol of the tertiary NICU at the University of Bologna in a prospective study of long-term sequelae of congenital infection. Forty-seven blood samples were obtained from 47 infants in the neonatal period: 34 were examined for pp65 antigenemia test and 44 for qualitative and quantitative polymerase chain reaction (PCR and qPCR). Sequelae at 12 months were evaluated in a group of 50 infants. RESULTS: Antigenemia was positive in only 10 of 34 samples of infected newborns (29.4% sensitivity). PCR was performed in 44 samples of infected newborns and was positive in all (100% sensitivity). qPCR showed a finding of > or =100 copies per 10(5) of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 10(5) PMNLs was <100. Between symptomatic and asymptomatic newborns, the mean values of viral blood load determined by qPCR turned out to be significantly higher in symptomatic newborns. Mean values of neonatal blood viral load were statistically higher in newborns who developed sequelae than in those who did not. Of 20 children with a neonatal viral blood load of <1000 copies per 10(5) PMNLs, 19 did not develop sequelae (negative predictive value: 95%), whereas 2 of 3 with a viral blood load of >10,000 copies did develop sequelae. CONCLUSIONS: Different viremia value ranges are correlated to a different risk of sequelae: approximately 70% sequelae were found in newborns with a qPCR higher than 10,000 copies per 10(5) PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia <1000 copies per 10(5) PMNLs has a negative predictive value of 95%. As an independent predictive factor of outcome, neonatal viremia is another useful element for neonatal counseling and therapeutic choices in symptomatic and asymptomatic newborns.

Central Nervous System Diseases↗

Monitoring for human cytomegalovirus infection in solid organ transplant recipients through antigenemia and glycoprotein N (gN) variants: evidence of correlation and potential prognostic value of gN genotypes.

Human cytomegalovirus (HCMV) ORF UL73 encodes the envelope glycoprotein gpUL73-gN, which shows seven genotypes (gN-1, gN-2, gN-3a, gN-3b, gN-4a, gN-4b, gN-4c). The goal of this study was to determine retrospectively the distribution of gN variants in solid organ transplant recipients with HCMV infection and to establish an association with parameters important for monitoring post-transplantation clinical course during a follow-up of up to 2 years. Peripheral blood leukocytes from 40 solid organ transplant recipients were analysed for pp65-antigen by immunofluorescence and gN genotyped by sequencing or RFLP analysis. A correlation between gN genotypes and antigenemia peak was found, showing a highly significant difference between gN-1 and gN-4b variants (P<0.005). In particular, gN-1 seems to be associated with patients developing low level antigenemia (<50 pp65-positive cells/2 x 10(5) PBLs; PPV = 90%), whereas gN-4b predicts significantly higher values (>50 pp65-positive cells/2 x 10(5) PBLs; PPV = 80%). Furthermore, the onset of positive antigenemia is significantly earlier in patients infected with a gN-4b strain, compared with those infected by a gN-1 variant. Reported data further support a role for gN genotypes in HCMV pathogenesis. gN-1 and gN-4b show a significantly different virulence and could serve as early predictors for the progression of HCMV infection in transplant patients.

Adult↗

Impaired dendritic cell immunophenotype and function in heart transplant patients undergoing active cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) infects dendritic cells (DCs) in vitro and inhibits their maturation properties and their ability to stimulate T-cell proliferation and cytotoxicity. This study analyzed HCMV infection of DCs in vivo. METHODS: We compared blood DCs and monocyte-derived DCs from heart-transplant patients undergoing an acute HCMV infection with DCs obtained from HCMV-negative transplant patients. Diagnosis of active HCMV infection was established by antigenemia test. RESULTS: We detected viral RNA and antigens in defined DC subsets obtained from patients undergoing an active HCMV infection. In addition, we found an impaired immunophenotype in immature DCs from HCMV-positive subjects and a reduced ability of mature DCs from the same group of patients to stimulate allogenic T-cell proliferation. CONCLUSIONS: The impaired immunophenotype and function detected in DCs from transplant patients undergoing an active HCMV infection may be a mechanism used by the virus to interfere with early immune functions and thereby contributing to the HCMV-induced immunosuppression in these patients.

Antigens, CD↗

Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells.

BACKGROUND: Statins exert anti-inflammatory effects independently of cholesterol-lowering properties. Cytomegalovirus (CMV) infection appears to be implicated in the pathophysiology of atherosclerosis by inducing inflammatory modifications in endothelial cells, especially in immunosuppressed patients. We investigated whether the activity of statins can inhibit replication of CMV in human endothelial cells. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were infected with CMV and coincubated with fluvastatin at 0.1 and 0.2 micromol/L. Fluvastatin inhibited (P<0.001) CMV antigen expression, and this effect was dose related (P<0.001). Quantitative polymerase chain reaction showed that CMV DNA concentration was consistently lower in supernatants from fluvastatin-treated cells than in infected controls, and viral particle concentration was up to 30 times lower in 0.2 micromol/L fluvastatin-treated cells than in infected controls (10.5+/-0.9 versus 0.34+/-0.03 per 10(3) pfu/mL, P<0.001). Addition of mevalonate to treated cultures almost completely abolished fluvastatin inhibition of viral growth. Electrophoretic mobility shift assay showed that fluvastatin reduced nuclear factor-kappaB binding activity in CMV-infected cells. CONCLUSIONS: HMG-CoA inhibition by fluvastatin restrains CMV replication in HUVECs by inhibiting viral antigen expression, DNA synthesis, and viral particle production, conceivably by involving a reduction of nuclear factor-kappaB binding activity.

Antigens, Viral↗

Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection.

In most European countries, pregnant women are tested for cytomegalovirus (CMV) during the first trimester of pregnancy. Within the last 5 years, European laboratories have made significant progress in solving diagnostic problems linked to infection in pregnancy. With advances in CMV serology, the presence of anti-CMV immunoglobulin (Ig)M detected by a screening test such as enzyme immunoassay, can be confirmed by blot, identifying pregnant women undergoing an active or recent infection. Furthermore, primary infections that were proven if a seroconversion was observed or suspected in the presence of IgM, can now be readily diagnosed by disclosing the presence of anti-CMV low avidity in IgM-positive mothers, greatly reducing the number of women who should be considered at risk of transmitting the virus. Virologic maternal tests are not enough to diagnose a recent primary maternal CMV infection and the detection or quantification of CMV in maternal blood does not seem to be associated with a higher risk for fetal infection. A cohort of 1520 pregnant women considered at risk of transmitting the virus were followed in a longitudinal study at the University of Bologna. Women were identified as part of routine CMV screening in several Italian regions and were IgM-positive for CMV. We documented IgG seroconversion in 83 women and 1437 were IgM-positive by commercial kit.

Antibody Affinity↗

Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study.

BACKGROUND: Transplant coronary artery disease (TxCAD) is a major cause of long-term mortality after heart transplantation. Although vascular remodeling has been implicated in the pathophysiology of TxCAD, its determinants remain unknown. METHODS: Twenty-nine consecutive heart-transplant recipients prospectively received intravascular ultrasound (IVUS) of the left-anterior descending artery 1 and 12 months after transplant, with volumetric reconstruction of the proximal 30 mm. RESULTS: Overall, patients exhibited intimal volume increase (+83%, P<0.001), wheras vessel volume remained largely unchanged (+4%, P=0.270); consequently, overall lumen volume decreased (-6%, P=0.058). Among the clinical and laboratory variables, cytomegalovirus (CMV) infection requiring treatment (occurring in 12 patients), as assessed by pp65 antigenemia, was independently associated with the impaired ability of the vessel wall to enlarge in response to intimal volume increase, ultimately resulting in lumen loss (OR [95% CI]=0.098 [0.010-0.920]; P=0.042). However, adequate vessel response to intimal hyperplasia with consequent lumen preservation was observed in the remaining 17 patients who did not present CMV infection requiring treatment. CONCLUSIONS: The present study demonstrates that either adequate or inadequate coronary remodeling may occur during the first year after transplantation. Moreover, for the first time, it strongly suggests that remodeling modalities may be negatively influenced by the occurrence of clinically relevant CMV infection. Randomized prospective trials are warranted to investigate whether aggressive treatment of CMV infection may help prevent TxCAD.

Adult↗

Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome.

Human herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The virus has been found in the cerebrospinal fluid of many children with aseptic meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA detection in cord blood specimens of apparently healthy newborns and in fetuses following spontaneous abortions. A patient is described with early neonatal afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed by repeated detection of viral genome by polymerase chain reaction (PCR) in cerebrospinal fluid in the first days of life. At follow-up, magnetic resonance imaging (MRI) studies disclosed hyperintensities in the periventricular white matter and basal ganglia, associated with cerebral atrophy. Further follow-up at 18 months revealed poor neurological outcome with mild neurodevelopmental retardation, strabismus and hypertonia of legs. This report provides evidence of neurological involvement after HHV 6 vertical transmission, and the association with neurological sequelae.

Adult↗

Intrauterine cytomegalovirus infection and glycoprotein N (gN) genotypes.

BACKGROUND: Human cytomegalovirus (HCMV) clinical isolates display genetic polymorphisms, supposed to be related with strain-specific tissue-tropism and HCMV-induced immunopathogenesis. One recently discovered polymorphic gene is ORF UL73, encoding for the envelope glycoprotein gN. Among HCMV clinical strains, it shows four distinct genomic variants denoted as gN-1, gN-2, gN-3 and gN-4. OBJECTIVES: Aims of this study were to assess the prevalence of the different gN types in the populations examined and to investigate the possible relationship between genotypes and severity of congenital CMV disease. STUDY DESIGN: The gN genotyping was carried out by sequencing analysis of the HCMV ORF UL73. Comparisons were made by chi-square test and contingency tables. RESULTS: All the four gN genotypes can cause congenital infections and the overall distribution was as follows: gN-1, 23.6%; gN-2, 1.1%; gN-3, 12.9%; gN-4, 62.4%. None of them seems to be preferentially associated with vertical transmission or with acute outcome of congenital infection. However, considering the chronic outcome and long-term sequelae, there was a statistically significant (P<0.05) difference between congenitally infected infants with or without adverse chronic outcome. CONCLUSIONS: HCMV congenital infections, which displayed a prevalence of the gN-1 variants, seem to be associated with favorable chronic outcome.

Aborted Fetus↗

Vascular anastomoses in dichorionic diamniotic-fused placentas.

A case of fetal twin-to-twin cytomegalovirus infection through a dichorionic diamniotic (DiDi)-fused placenta prompted our search for possible vascular anastomoses in this type of placenta. This case and three additional DiDi-fused placentas were studied with gross (macro) sections and a three-dimensional (3D) stereomicroscopic technique. Two twins were dizygotic (they differed in gender and blood groups) and the other two were probably monozygotic. Macrosections and 3D-image analysis demonstrated side-to-side connections between small subchorionic vessels. These findings demonstrate that vascular anastomoses are present in DiDi-fused placentas.

Amnion↗

Horizontal in utero acquisition of cytomegalovirus infection in a twin pregnancy.

It is generally accepted that viral infections can be transmitted horizontally by direct or indirect contact with virus-excreting persons, and some viral infections can be transmitted vertically, either prenatally or perinatally, from mother to child. This report presents data strongly supporting a prenatal horizontal acquisition of human cytomegalovirus infection in a twin pregnancy.

Cytomegalovirus Infections↗

Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome.

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks' gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 10(3) genome equivalents (GE)/mL of females AF and 1.9 x 10(5) GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 x 10(4) GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.

Amniotic Fluid↗

Autoantibody appearance in cytomegalovirus-infected liver transplant recipients: correlation with antigenemia.

The presence of anti-endothelial cells (AECA), smooth muscle (SMA), antinuclear (ANA) and antimitochondrial (AMA) autoantibodies, and liver/kidney microsomal antibody type 1 (LKM1) was investigated retrospectively in sera of liver transplant patients and correlated with cytomegalovirus (CMV) infection as determined by the antigenemia test and with the appearance of acute or chronic allograft rejection. Indirect immunofluorescence analysis was carried out in sequential sera from 40 liver transplant patients. Ten out of 23 antigenemia-positive and none of the antigenemia-negative patients developed serum autoantibodies (P = 0.002, Fisher's exact test). Anti-endothelial cell autoantibodies were found in nine cases and SMA in four patients. Antinuclear antibodies were detected in one otherwise autoantibody-negative patient. All but one case of autoantibody positivity were observed in the high antigenemia group (P < 0.0001, Fisher's exact test). In all but one case, autoantibodies were detected in blood during the antigenemia phase and in most cases in coincidence with or after the antigenemia peak. Even though a statistically significant correlation was not found between autoantibody production and the development of acute or chronic allograft rejection, proportionally more acute rejection cases were observed in the autoantibody-positive than in the autoantibody-negative group. It has been speculated that CMV-induced endothelial damage may be a potent antigenic stimulus, which leads to the production of anti-endothelial cells autoantibodies. Anti-endothelial cell autoantibodies may represent not only a marker of cell injury but also contribute to the progression of the inflammatory response leading to the exposure of tissue-privileged self antigens and the induction of other autoantibodies such as SMA.

Adult↗