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Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion (IUT). This study investigates the long-term temporal patterns in the epidemiology of B19V and evaluates the impact on fetal hydrops, by combining data on B19V infections from the Dutch Sentinel Surveillance system in the period 1990 to 2023, Dutch blood banking data and hospital data on fetal hydrops. Using wavelet analysis, we identified annual epidemic cycles in the Netherlands in the period 1990–2019 and we identified superimposed multiannual cycles in the period 1990–2009. After 2009, no multiannual cycle could be identified, although the incidence fluctuated and correlates with number of IUT performed. As of 2020, weekly reports of B19V infection demonstrated a historically low incidence and B19V-DNA positive blood donors were nearly absent. From May 2020 to May 2023, no IUT for B19V-related hydrops was performed. In the spring of 2023, B19V infections re-emerged, reaching pre-pandemic epidemic levels. Due to the changes in B19V epidemiology over the last 30 years and the near-absence of B19V during the COVID-19 pandemic, the resulting low immunity levels may lead to rebound outbreaks. Alertness to severe complications such as fetal hydrops is warranted. [ABSTRACT FROM AUTHOR]

This article describes the age distribution and clinical characteristics of 124 patients with serological evidence of recent cytomegalovirus (CMV) infection. As indicated by a high level of anti-CMV IgM and the presence of low-avidity anti-CMV IgG, in the absence of serological evidence of recent infection with Epstein-Barr virus, hepatitis A or B virus, or Toxoplasma gondii. The clinical characteristics of these 124 patients were evaluated retrospectively, yielding a wide range of symptoms, signs, and laboratory findings.

Rapid identification of the rise and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern remains critical for monitoring of the efficacy of diagnostics, therapeutics, vaccines, and control strategies. A wide range of SARS-CoV-2 next-generation sequencing (NGS) methods have been developed over the last years, but cross-sequence technology benchmarking studies have been scarce. In the current study, 26 clinical samples were sequenced using five protocols: AmpliSeq SARS-CoV-2 (Illumina), EasySeq RC-PCR SARS-CoV-2 (Illumina/NimaGen), Ion AmpliSeq SARS-CoV-2 (Thermo Fisher), custom primer sets (Oxford Nanopore Technologies (ONT)), and capture probe-based viral metagenomics (Roche/Illumina). Studied parameters included genome coverage, depth of coverage, amplicon distribution, and variant calling. The median SARS-CoV-2 genome coverage of samples with cycle threshold (Ct) values of 30 and lower ranged from 81.6 to 99.8% for, respectively, the ONT protocol and Illumina AmpliSeq protocol. Correlation of coverage with PCR Ct values varied per protocol. Amplicon distribution signatures differed across the methods, with peak differences of up to 4 log10 at disbalanced positions in samples with high viral loads (Ct values ≤ 23). Phylogenetic analyses of consensus sequences showed clustering independent of the workflow used. The proportion of SARS-CoV-2 reads in relation to background sequences, as a (cost-)efficiency metric, was the highest for the EasySeq protocol. The hands-on time was the lowest when using EasySeq and ONT protocols, with the latter additionally having the shortest sequence runtime. In conclusion, the studied protocols differed on a variety of the studied metrics. This study provides data that assist laboratories when selecting protocols for their specific setting. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to estimate long-term impairment attributable to congenital cytomegalovirus infection (cCMV).Method: This nationwide cohort study retrospectively assessed cCMV in children born in 2008 in the Netherlands, testing 31 484 stored neonatal dried blood spots. Extensive medical data of cCMV-positive children (n=133) and matched cCMV-negative comparison children (n=274) up to 6 years of age were analysed.Results: Moderate to severe long-term impairment was diagnosed in 24.8% (33 out of 133) of all cCMV-positive children (53.8% in symptomatic, 17.8% in asymptomatic), compared with 12.0% (33 out of 274) of cCMV-negative children. Sensorineural hearing loss was seen only in five cCMV-positive children (3.8%). Developmental delays were diagnosed more often in cCMV-positive children than cCMV-negative children: motor (12.0% vs 1.5%), cognitive (6.0% vs 1.1%), and speech-language (16.5% vs 7.3%). Long-term impairment in multiple domains was more frequent in symptomatic (19.2%) and asymptomatic (8.4%) cCMV-positive children than cCMV-negative children (1.8%).Interpretation: Children with cCMV were twice as likely to have long-term impairment up to the age of 6 years, especially developmental delays and sensorineural hearing loss, than cCMV-negative comparison children, with a risk difference of 12.8%. These insights into the risk of cCMV-associated impairment can help optimize care and stimulate preventive measures.What This Paper Adds: Congenital cytomegalovirus infection (cCMV) leads to impairment in 25% of cases. Fifty per cent of children with cCMV symptoms at birth have long-term impairment. The risk difference of moderate to severe long-term impairment between children with and without cCMV is 13%, attributable to cCMV. cCMV leads to motor, cognitive, and speech-language developmental delay in children. [ABSTRACT FROM AUTHOR]

Virus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the components to viral clearance remains unclear. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 102 hospitalised patients with moderate and severe COVID-19 in a longitudinal design. Delayed viral clearance was associated with more severe disease and was associated with higher levels of SARS-CoV-2-specific (neutralising) antibodies over time, increased numbers of neutrophils, monocytes, basophils, and a range of pro-inflammatory cyto-/chemokines illustrating ongoing, partially Th2 dominating, immune activation. In contrast, early viral clearance and less critical illness correlated with the peak of neutralising antibodies, higher levels of CD4 T cells, and in particular naïve CD4+ T cells, suggesting their role in early control of SARS-CoV-2 possibly by proving appropriate B cell help. Higher counts of naïve CD4+ T cells also correlated with lower levels of MIF, IL-9, and TNF-beta, suggesting an indirect role in averting prolonged virus-induced tissue damage. Collectively, our data show that naïve CD4+ T cell play a critical role in rapid viral T cell control, obviating aberrant antibody and cytokine profiles and disease deterioration. These data may help in guiding risk stratification for severe COVID-19. [ABSTRACT FROM AUTHOR]

Objectives To assess the total systemic antiviral use in Europe and to identify the antiviral substances most commonly used. Methods Within the European Surveillance of Antimicrobial Consumption (ESAC; www.esac.ua.ac.be), using the anatomical therapeutic chemical (ATC) classification and defined daily dose (DDD) measurement unit, data on total (out- and inpatient) systemic antiviral use (ATC J05), aggregated at the level of the active substance, were collected for 2008, and use was expressed in DDD (WHO ATC/DDD, version 2010) per 1000 inhabitants per day (DID). Antiviral substances were grouped according to their main indication. Results In Europe, 12 countries (Belgium, Croatia, Denmark, Estonia, Finland, France, Hungary, Italy, Luxembourg, Russia, Slovenia and Sweden) provided total (out- and inpatient) data and 4 countries (Austria, the Netherlands, Portugal and Norway) provided outpatient data only. Total systemic antiviral use varied by a factor of 10.95 between the country with the highest (3.53 DID in France) and the country with the lowest (0.32 DID in Croatia) use. HIV/AIDS antivirals represented more than 50% of the total antiviral use in most countries. The amount and spectrum of antivirals used varied greatly between countries. Conclusions Our study demonstrated a wide variation of total systemic antiviral use in several European countries, as striking as that of outpatient systemic antibiotic, antimycotic and antifungal use. The variation is mainly determined by the use of HIV/AIDS antivirals. These observations should stimulate further analysis to understand the variation of specific antiviral substances. The ESAC data facilitate auditing of antiviral prescriptions and evaluation of the implementation of guidelines and public health policies. [ABSTRACT FROM PUBLISHER]

Exacerbations are major contributors to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and respiratory bacterial and viral infections are an important trigger. However, using conventional diagnostic techniques, a causative agent is not always found. Metagenomic next-generation sequencing (mNGS) allows analysis of the complete virome, but has not yet been applied in COPD exacerbations. To study the respiratory virome in nasopharyngeal samples during COPD exacerbations using mNGS. 88 nasopharyngeal swabs from 63 patients from the Bergen COPD Exacerbation Study (2006–2010) were analysed by mNGS and in-house qPCR for respiratory viruses. Both DNA and RNA were sequenced simultaneously using an Illumina library preparation protocol with in-house adaptations. By mNGS, 24/88 samples tested positive. Sensitivity and specificity, as compared with PCR, were 96% and 98% for diagnostic targets (23/24 and 1093/1120, respectively). Additional viral pathogens detected by mNGS were herpes simplex virus type 1 and coronavirus OC43. A positive correlation was found between Cq value and mNGS viral normalized species reads (log value) (p = 0.002). Patients with viral pathogens had lower percentages of bacteriophages (p<0.001). No correlation was found between viral reads and clinical markers. The mNGS protocol used was highly sensitive and specific for semi-quantitative detection of respiratory viruses. Excellent negative predictive value implicates the power of mNGS to exclude any pathogenic respiratory viral infectious cause in one test, with consequences for clinical decision making. Reduced abundance of bacteriophages in COPD patients with viral pathogens implicates skewing of the virome during infection, with potential consequences for the bacterial populations, during infection. [ABSTRACT FROM AUTHOR]

The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological, and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with PPMV-1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naive pigeons. Both patients were likely infected by contact with infected pigeons or doves. Given the large populations of feral pigeons with PPMV-1 infection in cities, increasing urbanization, and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend testing for avian paramyxovirus type 1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified. [ABSTRACT FROM AUTHOR]

Congenital Cytomegalovirus infection (cCMV) is the leading infection in determining permanent long-term impairments (LTI), and its pathogenesis is largely unknown due to the complex interplay between viral, maternal, placental, and child factors. The cellular activity, considered to be the result of the response to exogenous and endogenous factors, is captured by the determination of gene expression profiles. In this study, we determined whole blood transcriptomes in relation to cCMV, CMV viral load and LTI development at 6 years of age by using RNA isolated from neonatal dried blood spots (DBS) stored at room temperature for 8 years. As DBS were assumed to mainly reflect the neonatal immune system, particular attention was given to the immune pathways using the global test. Additionally, differential expression of individual genes was performed using the voom/limma function packages. We demonstrated feasibility of RNA sequencing from archived neonatal DBS of children with cCMV, and non-infected controls, in relation to LTI and CMV viral load. Despite the lack of statistical power to detect individual genes differences, pathway analysis suggested the involvement of innate immune response with higher CMV viral loads, and of anti-inflammatory markers in infected children that did not develop LTI. Finally, the T cell exhaustion observed in infected neonates, in particular with higher viral load, did not correlate with LTI, therefore other mechanisms are likely to be involved in the long-term immune dysfunction. Despite these data demonstrate limitation in determining prognostic markers for LTI by means of transcriptome analysis, this exploratory study represents a first step in unraveling the pathogenesis of cCMV, and the aforementioned pathways certainly merit further evaluation. [ABSTRACT FROM AUTHOR]

Classic human polyomaviruses (JC and BK viruses) become pathogenic when reactivating from latency. For the rare skin disease trichodysplasia spinulosa, we show that manifestations of the causative polyomavirus (TSPyV) occur during primary infection of the immunosuppressed host. High TSPyV loads in blood and cerebrospinal fluid, sometimes coinciding with cerebral lesions and neuroendocrine symptoms, marked the acute phase of trichodysplasia spinulosa, whereas initiation and maturation of TSPyV seroresponses occurred in the convalescent phase. TSPyV genomes lacked the rearrangements typical for reactivating polyomaviruses. These findings demonstrate the clinical importance of primary infection with this rapidly expanding group of human viruses and explain the rarity of some novel polyomavirus-associated diseases. [ABSTRACT FROM AUTHOR]

Congenital CMVinfection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecularmarkers of Tand B cell numbers in neonatal dried blood spots of 99 children with cCMVand 54 children without cCMV: dRec-cJa signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igk-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vd1-Jd1, and Vd2-Jd1 rearrangements. Of this cohort, clinical symptoms at birth and LTI at 6 y of age were recorded. Neonates with cCMV had fewer TCR excision circles in their blood than non-infected controls. Furthermore, cCMV infection was associated with increased numbers of gd T cells and B cells, and these numbers were positively correlated with CMV viral load in the dried blood spots. Infected children with a better long-term outcome had higher numbers of B cells at birth than thosewho developed LTI; no difference in B cell replication was observed. The potential protective role of B cells in controlling cCMV-related disease and the clinical value of this marker as a predictor of long-term outcome merit further evaluation. [ABSTRACT FROM AUTHOR]

Background An inverse association between markers of exposure to foodborne and orofecal pathogens and allergic sensitization has been reported. However, the findings of epidemiological studies have not been consistent. This study investigated the relationship between antibodies to hepatitis A, Toxoplasma gondii and salmonella and allergic sensitization to food and aeroallergens in children from different geographical areas. Methods Specific IgE and/or skin prick testing against food and aeroallergens were measured in children from 6 to 12 years of age residing in Greece, the Netherlands, China, India and Russia. Seropositivity to the three pathogens was measured, and data on potential confounders were collected using questionnaire. Results Data from 800 children (126 from Athens; 248 from Utrecht; 110 from Hong Kong; 119 from urban Tomsk; and 197 from rural Tomsk) could be analysed. The highest percentage of positive serology to salmonella was found in Hong Kong (46.4%), to T. gondii in urban Tomsk (13.4%) and to hepatitis A in Athens (71.2%). Although not significant, T. gondii seropositivity tends to be negatively associated, and hepatitis A seropositivity tends to be positively associated with allergic sensitization. Conclusion Inconsistent associations were observed between allergic sensitization to food and aeroallergens and markers of exposure to two common foodborne pathogens. The association with T. gondii tends to be negative, consistent with the 'hygiene hypothesis', but the association with hepatitis A tends to be positive. Taken together, there is no clear evidence that past exposure to foodborne and orofecal pathogens protects against allergic sensitization to food or aeroallergens. [ABSTRACT FROM AUTHOR]

The pandemic influenza A (H1N1) 2009 virus (pH1N1) contains novel gene segments of zoonotic origin that lack virulence and antiviral resistance markers. We aimed to evaluate the applicability and accuracy of mass spectrometry-based comparative sequence analysis (MSCSA) to detect genetic mutations associated with increased virulence or antiviral resistance in pH1N1. During the 2009 H1N1 pandemic, routine surveillance specimens and clinical antiviral resistance monitoring specimens were analyzed. Routine surveillance specimens obtained from 70 patients with pH1N1 infection were evaluated for mutations associated with increased virulence (PB1-F2, PB2 and NS1 genes) or antiviral resistance (neuraminidase gene, NA) using MSCSA and Sanger sequencing. MSCSA and Sanger sequencing results revealed a high concordance (nucleotides >99%, SNPs ∼94%). Virulence or resistance markers were not detected in routine surveillance specimens: all identified SNPs encoded for silent mutations or non-relevant amino acid substitutions. In a second study population, the presence of H275Y oseltamivir resistant virus was identified by real-time PCR in 19 of 35 clinical antiviral resistance monitoring specimens obtained from 4 immunocompromised patients with ≥14 days prolonged pH1N1 excretion. MSCSA detected H275Y in 24% (4/19) of positive specimens and Sanger sequencing in 89% (17/19). MSCSA only detected H275Y when the mutation was dominant in the analyzed specimens. In conclusion, MSCSA may be used as a rapid screening tool during molecular surveillance of pH1N1. The low sensitivity for the detection of H275Y mutation in mixed viral populations suggests that MSCSA is not suitable for antiviral resistance monitoring in the clinical setting. [ABSTRACT FROM AUTHOR]

Varicella zoster virus episodes in hematological patients were systematically studied retrospectively, and viral persistence for at least 7 days was found in 59% of the episodes. Of the persistent episodes, 50% were complicated and 27% were caused by resistant virus.Background. Varicella zoster virus (VZV) infections are a relevant cause of morbidity and mortality in hematological patients and especially in hematopoietic stem cell transplant (HSCT) recipients. The present study aimed to investigate the prevalence and clinical significance of viral persistence and antiviral resistance by systematically analyzing all episodes of VZV diagnosed in our laboratory in pediatric and adult hematological patients between 2007 and 2010.Methods. Patient charts were reviewed to document patient and disease characteristics. VZV loads were determined in all available clinical samples from the day of diagnosis and thereafter. Persistent VZV infection was defined as a VZV infection that lasted at least 7 days. Analysis of resistance was performed in all patients with persistent VZV infection by sequence analysis of viral thymidine kinase and DNA polymerase genes.Results. In total, 89 episodes occurred in 87 patients, of whom 65 were recipients of an allogeneic HSCT. Follow-up samples were available in 54 episodes. Persistent VZV was demonstrated in 32 of these episodes (59%). Complications occurred in 16 of the persistent episodes (50%) vs 2 of 22 nonpersistent episodes (9%). Mutations possibly associated with resistance were found in 27% of patients with persistent VZV, including patients with treatment-unresponsive dermatomal zoster that progressed to severe retinal or cerebral infection.Conclusions. In hematological patients, VZV-related complications occur frequently, especially in persistent infections. Antiviral resistance is a relevant factor in persistent infections and needs to be investigated in various affected body sites, especially when clinical suspicion of treatment failure arises. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to an article on testing newborns for congenital cytomegalovirus (CMV) infection in the previous issue.

The factors that cause prolonged human influenza virus respiratory tract infection and determine its clinical impact and the development of drug-resistant viruses are unclear. During a 3-year period, symptomatic influenza virus excretion for ⩾2 weeks was observed among 8 immunocompromised patients and found to be associated with lymphocytopenia at onset (8 of 8 patients) more often than with granulocytopenia (2 of 8 patients) or monocytopenia (2 of 8 patients). Six (75%) of 8 patients developed influenza lower respiratory tract infection (10 episodes), and receipt of oseltamivir treatment was significantly associated with clinical improvement (8 of 8 episodes vs. 0 of 2 untreated episodes; P = .02). Complete viral clearance was strongly correlated with lymphocyte reconstitution (P = .04) but was never observed during the first 2 weeks after oseltamivir treatment. Neuraminidase inhibitor-resistant influenza viruses emerged in 2 (67%) of 3 patients eligible for resistance analysis. In conclusion, prolonged influenza virus infection was associated with lymphocytopenia, influenza lower respiratory tract infection, and frequent development of drug resistance during antiviral therapy. Clinical improvement in influenza lower respiratory tract infection is observed during oseltamivir treatment, but complete viral clearance is dependent on lymphocyte reconstitution, irrespective of receipt of antiviral medication. [ABSTRACT FROM AUTHOR]

The article presents a medical research study which examined nosocomial transmission of the oseltamivir-resistant influenza A(H1N1) virus in a cluster of patients. Two hematopoietic stem cell transplant recipients and an elderly patient who developed nosocomial influenza A virus infection following exposure to an index patient comprised the cluster of patients that was investigated. Medical records, polymerase chain reaction and culture, phenotypic oseltamivir and zanamivir susceptibility, and hemagglutinin chain 1 (HA1) gene and NA gene sequence analysis were reviewed. Researchers found that the seasonal viruses with NA gene H274Y mutation are transmitted and retain significant lethality and pathogenicity in high-risk hospital patients.

Objectives: Disseminated adenovirus (AdV) infections following allogeneic stem cell transplantation (allo-SCT) are increasingly recognised, particularly in children. This study evaluated the clinical relevance of disseminated AdV infections in adult allo-SCT recipients, after different conditioning regimens. Methods: In a cohort of 107 adult allo-SCT recipients, receiving either reduced intensity conditioning (RIC, n = 48) or myeloablative conditioning (MAC, n = 59), AdV DNA levels in plasma were determined retrospectively at 1, 3 and 6 months following transplantation. Results of this screening regimen were compared with a cohort of 58 paediatric allo-SCT recipients, in whom AdV DNA load was monitored prospectively, as part of a pre-emptive treatment strategy. In positive cases, the course of AdV DNA load and clinical outcome were assessed. Results: AdV DNA levels ≥1000 copies/mL were detected in five adults (4.7%) and eight children (13.8%). Screening for AdV viraemia at 1, 3 and 6 months would have detected seven of eight paediatric patients. One adult, receiving MAC, died with disseminated AdV disease and in four (three RIC and one MAC) AdV viraemia was transient without clinical symptoms specifically attributable to AdV. Seven paediatric patients with AdV viraemia were pre-emptively treated with ribavirin or cidofovir and in three of them disseminated AdV infection was related to a fatal outcome. Conclusions: Disseminated AdV infections following allo-SCT was a rare event in the adults and cause morbidity in a minority of these patients. In four of five adult patients, spontaneous clearance of AdV viraemia occurred. Results did not differ between the conditioning regimens that were applied in the adult cohort. [ABSTRACT FROM AUTHOR]

Objectives: Facilitate risk assessment of vital complications in fetuses of pregnancies affected by acute parvovirus B19 (B19V) infection. Design: Study of the natural course of maternal B19V infection in four cases, from early pregnancy on. Setting: University Medical Center in the Netherlands. Population: Pregnant mothers attending obstetric services. Methods: Serial measurements of the maternal and fetal or neonatal viral load and antibody responses. Main Outcome Measures: Maternal and fetal/neonatal serum B19V viral DNA load and specific IgM and IgG antibodies in maternal serum. Results: Peak viral load levels occurred within 1 week after maternal infection and peak IgM levels were observed 1 week after the peak viral load levels. Approximation of IgG and IgM ratios usually took place 4 weeks after infection. Vertical transmission occurred 1–3 weeks after maternal infection, suggesting that fetal infection occurs during the maternal peak viral load. Conclusions: Maternal B19V DNA load levels and IgM responses are useful to estimate the risk of parvovirus B19-associated fetal complications. The maternal peak viral load directly precedes the onset of fetal infection and may be used to indicate the stage of intrauterine B19V infection. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation and may progress to life-threatening lymphoproliferative disease (EBV-LPD) in the absence of adequate EBV-specific T cell immunity. Quantification of EBV DNA load in asymptomatic individuals who are at risk is a useful (although not entirely predictive) indicator of progression to EBV-LPD and guide for preemptive treatment with CD20 antibodies. Methods. With the aim of improving the identification of patients at risk, we retrospectively analyzed, within a cohort of 25 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD, the pattern of T cell reconstitution during EBV reactivation in all preemptively treated patients (8 patients). Results. In 6 of 8 cases, a significant T cell reconstitution (i.e., a CD3+ T cell count of >300 cells/μL) was documented during EBV reactivation, which included an expansion of EBV-specific memory T cells, as shown by human leukocyte antigen class I tetramer analysis. Additional evidence for the antiviral potential of this T cell reconstitution was obtained prospectively from a cohort of 14 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD. EBV reactivation occurred in 3 patients. Preemptive treatment was successfully withheld for 2 of these patients in light of concurrent (EBV-specific) T cell recovery. Conclusion. We conclude that analysis of the level of (EBV-specific) T cell reconstitution during EBV reactivation is an important second parameter, in addition to quantification of EBV DNA load, that will be instrumental in a more accurate definition of patients at risk for EBV-LPD who, given their immunoincompetence, will be most certainly dependent on preemptive interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Simultaneous pancreas-kidney (SPK) transplantation in type 1 diabetic patients requires immunotherapy against allo- and autoreactive T-cells. Cytomegalovirus (CMV) infection is a major cause for morbidity after transplantation and is possibly related to recurrent autoimmunity. In this study, we assessed the pattern of CMV viremia in SPK transplant recipients receiving either antithymocyte globulin (ATG) or anti-CD25 (daclizumab) immunosuppressive induction therapy. RESEARCH DESIGN AND METHODS -- We evaluated 36 SPK transplant recipients from a randomized cohort that received either ATG or daclizumab as induction therapy. Patients at risk for CMV infection received oral prophylactic ganciclovir therapy. The CMV DNA level in plasma was measured for at least 180 days using a quantitative real-time PCR. Recipient peripheral blood mononuclear cells were cross-sectionally HLA tetramer-stained for CMV-specific CD8+ T-cells. RESULTS -- Positive CMV serostatus in donors was correlated with a higher incidence of CMV viremia than negative serostatus. In patients at risk, daclizumab induction therapy significantly prolonged CMV-free survival. CMV viremia occurred earlier and was more severe in patients with rejection episodes than in patients without rejection episodes. CMV-specific CD8+ T-cell counts were significantly lower in patients developing CMV viremia than in those who did not. CONCLUSIONS -- Despite their comparable immunosuppressive potential, daclizumab is safer than ATG regarding CMV infection risk in SPK transplantation. ATG-treated rejection episodes are associated with earlier and more severe infection. Furthermore, high CMV-specific tetramer counts reflect antiviral immunity rather than concurrent viremia because they imply low viremic activity. These findings may prove valuable in the discussion on both safety of induction therapy and recurrent autoimmunity in SPK and islet transplantation. [ABSTRACT FROM AUTHOR]

Background. Human adenovirus (HAdV) infections are increasingly frequent complications of allogeneic stem-cell transplantation (SCT), especially in children. Only a few data on the correlation between immune recovery and the course of HAdV infection are available, and data on HAdV-specific responses are lacking. Methods. In a prospective study, we determined the correlation between the HAdV DNA load in plasma and lymphocyte reconstitution in 48 children after allogeneic SCT. Additionally, HAdV-specific humoral and cellular immune responses were investigated. Results. HAdV infection occurred in 21 patients (44%), and, in 6 of these patients, the infection progressed to viremia, as demonstrated by the presence of HAdV DNA in plasma. Low lymphocyte counts at the onset of infection were predictive of HAdV viremia. Survival of patients with HAdV viremia was associated with an increase in lymphocyte counts during the first weeks after infection. In these patients, HAdV-specific CD4+ T cell responses, as well as increases in titers of neutralizing antibody, were detected after clearance of HAdV DNA from plasma. Conclusions. Lymphocyte reconstitution appears to play a crucial role in clearance of HAdV viremia and survival of the host, warranting further development of therapeutic interventions aimed at improving immune. [ABSTRACT FROM AUTHOR]

Reports on the cases of parainfluenza 4 virus (hPIV4) infections in infants detected by a multiplex real-time polymerase chain reaction (PRC) method. Medical history of the infants; Information on PCR method; Respiratory illnesses that are caused by hPIV4.

Adenoviruses are increasingly recognised as viral pathogens that can cause fatal infections in immunocompromised patients, particularly recipients of haematopoietic stem-cell grafts. Adenovirus infections are not easily diagnosed and the development of a severe infection cannot be predicted by standard culture techniques. In a pilot study, we investigated the value of adenovirus DNA detection in serum as a marker of disseminated disease in 14 patients with defined patterns of adenovirus infections. The results show that the appearance of adenoviral DNA in serum preceded the development of a severe or fatal adenovirus infection. Because proper management is dependent on early diagnosis and differentiation from other conditions, this test may be a valuable tool in the management of adenovirus infection. [ABSTRACT FROM AUTHOR]