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Immunohistological detection of human parvovirus B19 in formalin-fixed, paraffin-embedded tissues.

Human parvovirus B19 is a cause of aplastic crises in patients with haemolytic anaemias, prolonged bone marrow failure in the immunosuppressed, and fetal death secondary to non-immune hydrops. The immunohistological detection of parvovirus B19 in formalin-fixed, paraffin-embedded tissues has not previously been reported, and definitive diagnosis of infection in such specimens has relied on the use of specialized DNA hybridization and amplification techniques. A new monoclonal antibody to B19 capsid proteins, R92F6, was found to be capable of labelling infected cells in paraffin-embedded tissues from all 19 cases of parvovirus-related fetal hydrops tested, and in bone marrow from a child with congenital immunodeficiency and chronic parvovirus infection. Viral antigen was detected both in cytoplasmic and in nuclear distributions using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique without preceding proteolytic digestion. The viral epitope recognized appears to be highly conserved, as specimens were obtained over a 13-year period from widely spaced locations in the U.K. Antibody R92F6 should facilitate rapid diagnosis of parvovirus B19 infection in routinely processed and archival specimens.

Antibodies, Viral

Tracing the evolution and diversity of human parvovirus B19 across human history.

Human parvovirus B19 (B19V) is an ubiquitously spread, exclusively human pathogen, mainly posing risks to children, as well as pregnant and immunocompromised individuals. Despite evidence of B19V infection of human populations as far back as 7,000 years, the evolutionary history of B19V remains poorly understood. In this study, we present B19V genomic data from the remains of 53 globally distributed individuals spanning more than 8,000 years, including 7 children. Our findings suggest that the most recent common ancestor of all present B19V lineages existed around 12,000 years ago, at the end of the last Ice Age. Additionally, we identified an extinct Eurasian clade that participated in the recombination event that led to the emergence of B19V genotype 2 (GT-2). We date this event to ∼3,200-1,800 BP, potentially in the greater Mediterranean area. Our study shows aspects of how ancient parvovirus variants arose, disseminated, and impacted human health through time.

ancient DNA

Estimating the impact of parvovirus B19 outbreaks on congenital anomalies and fetal outcomes in Wales.

OBJECTIVES: Parvovirus B19 (B19V) is a common infection that can cause complications in pregnancy. Outbreaks of B19V in Europe and the UK were recorded in 2024. We aimed to describe the epidemiology of maternal parvovirus in Wales and to investigate associated fetal outcomes widely and in 2024 specifically. STUDY DESIGN: A retrospective observational study. METHODS: All cases of maternal B19V reported to the Congenital Anomaly Register Information Service (CARIS) were analysed. Maternal risk factors included gestational age at the time of infection and maternal age. Spatio-temporal analysis was performed to look for clusters. Poisson regression was used to model incidence of maternal B19V over time. Fetal outcomes were tested for association with risk factors using linear regression and Fisher's exact test. Outcomes and congenital anomalies were descriptively analysed. RESULTS: Between 1998 and 2025, there were 79 cases of maternal B19V across 81 fetuses, mostly reported in South Wales (74/81, 91.3%). There were 24 (29.6%) cases of at least one confirmed congenital anomaly and 57 (70.3%) cases reporting no anomalies; 53 (93%) of these cases had a positive outcome. Congenital anomalies were associated with worse fetal outcomes. Excluding terminations, the overall fetal survival rate was 88%. No association between maternal risk factors and fetal outcome was identified. There was an increase in cases in 2024 with an increase in fetal losses. CONCLUSIONS: The 2024 European B19V outbreak led to an increase in maternal cases and negative fetal outcomes in Wales.

Humans

Spontaneous resolution of nonimmune hydrops fetalis secondary to human parvovirus B19 infection.

Many instances of nonimmune hydrops fetalis ascribed to human parvovirus B19 have been reported. The leading proposed pathophysiologic mechanism of hydrops in affected fetuses is viral invasion of red blood cell progenitors, causing a profound reticulocytopenic fetal anemia. Although the natural history of fetal parvovirus infection remains to be elucidated fully, there have been recent reports of funipuncuture and intrauterine blood transfusions to diagnose and manage this problem. We report two pregnancies in which parvovirus-related hydrops fetalis was observed to resolve without intervention, followed by uncomplicated vaginal deliveries of healthy infants. These observations emphasize the need for further investigation before recommending routine fetal blood transfusion in affected cases.

Adolescent

Diagnosis of human parvovirus B19 infections by polymerase chain reaction.

The polymerase chain reaction (PCR) was used for detecting parvovirus B19 DNA in clinical specimens. A pair of oligonucleotide primers spanning the PstI-fragment of the B19 virus genome was used for PCR, and a PCR product of 727 bp was amplified. B19 virus DNA was detected in all sera (n = 26) of individuals in the incubation period and acute phase of infection. PCR was useful for detecting viral B19 DNA in amniotic fluid and fetal blood of hydropic fetuses, confirming fetal B19 virus infection.

Base Sequence

Nanopore-based, long-range Parvovirus B19 amplicon sequencing for near-whole genome characterization.

BACKGROUND: Whole-Genome Sequencing (WGS) enables monitoring of genomic variation and evaluation of diagnostic PCR assays. However, WGS data for Parvovirus B19 (B19V) remains limited despite its relevance for clinical care and transfusion safety. To increase the availability of high-quality B19V genomic data, a near-WGS protocol was developed and validated. METHOD: The protocol combines long-range PCR to generate a 4.6-kb amplicon, covering ∼82% of the B19V genome, with Oxford Nanopore sequencing. Validation was performed using six reference samples and nineteen B19V-positive donor plasma samples. RESULTS: After quality control, samples achieved a median sequencing depth of 152x. Sequences generated from the six reference samples showed 100% concordance with previously published data. Genomic analysis of donor samples explained atypical amplification profiles observed during routine PCR screening. CONCLUSION: The newly developed protocol provides a scalable method for B19V genome characterization, enabling assessment of oligonucleotide-binding regions for PCR assay monitoring and facilitating the generation of genomic data for future epidemiological investigations.

PCR assay monitoring

Human parvovirus B19 infection in hemophiliacs first infused with two high-purity, virally attenuated factor VIII concentrates.

Human parvovirus B19 can be transmitted by coagulation factor concentrates and is highly resistant to virucidal methods. To evaluate whether the additional removal of virus by chromatographic methods during the manufacture of high-purity concentrates reduces the risk of B19 transmission, we have prospectively evaluated the rate of anti-B19 seroconversion in two groups of susceptible (anti-B19 negative) hemophiliacs infused with high-purity, heated (pasteurized) or solvent-detergent-treated factor VIII concentrates. Both products infected a relatively high proportion of patients (nine of 20).

Detergents

Impact of child day care on infectious diseases in adults.

The authors review diseases that occur in day care centers and their impact on day care providers and parents. Acute infections of the gastrointestinal and respiratory tracts are the most commonly transmitted illnesses from children in day care centers to adults. The most important infections acquired by adults are those with the potential for significant clinical morbidity, such as hepatitis A, or those that generate concern, such as cytomegalovirus and parvovirus B19, because of their potential to produce congenital infections in pregnant women.

Adult

Bone marrow necrosis and human parvovirus associated infection preceding an Ph1+ acute lymphoblastic leukemia.

A case of bone marrow necrosis associated with a serologically documented recent Parvovirus B 19 infection which preceded the development of PH1+ acute lymphoblastic leukemia is reported. No conclusions can be drawn on the basis of a single case but the question of the role of human Parvovirus B19 in the pathogenesis of bone marrow necrosis is discussed. It is suggested that the virus may act as a co-factor for the induction of bone marrow necrosis, in some cases.

Adult

[An adult case of transverse myelitis with erythema infectiosum].

We reported an adult case of transverse myelitis with erythema infectiosum. A 33-year-old female was admitted to Kyoto University Hospital because of a weakness in the lower extremities and "cloth-wearing" sensation of the trunk and legs. One month before admission, she became febrile and developed a symmetrical erythema on the extremities. At the same time she noticed a slight weakness of the legs and numbness in her fingers and toes, which disappeared next few days. A week later, she again developed a fever, severe weakness of the legs and "cloth-wearing" sensation on the trunk, and erythema appeared on the cheek. Physical examination on admission revealed a weakness and hyperreflexia in the extremities, in particular, knee and ankle jerk, and hypesthesia of the trunk and legs below the level of Th6. Cerebrospinal fluid (CSF) examination revealed 181/mm3 cells (mononuclear cell dominant) and 30 mg/dl protein. Magnetic resonance imaging, CT and electrophysiological studies indicated no abnormalities. IgM antibody against human parvovirus (B19) was detected in the serum and CSF. She was diagnosed as transverse myelitis with parvovirus infection and was medicated with prednisolone 40-60 mg/day, and improved gradually with the residua of a mild weakness of the legs and hypesthesia on the trunk between the level of Th6 and Th10.

Adult

Rapid pan-microbial metagenomics for pathogen detection and personalised therapy in the intensive care unit: a single-centre prospective observational study.

BACKGROUND: Most clinical metagenomic studies do not provide rapid results, detect pathogens from all microbial kingdoms, or measure clinical impacts. We aimed to evaluate the feasibility, performance, and clinical impacts of a rapid pan-microbial respiratory metagenomic service for patients admitted to intensive care units (ICUs). METHODS: This was a single-centre observational study of a rapid metagenomics service that tests respiratory samples from ICU patients at Guy's and St Thomas' hospitals, London, UK, between Dec 5, 2023, and April 12, 2024. Testing used a previously published pan-microbial metagenomics workflow, which simultaneously detects bacteria, fungi, and DNA and RNA viruses; provides same-day preliminary results after 2 h; and provides final results after 24 h. Patients were included if they were aged 18 years or older, admitted to the ICU, had confirmed respiratory failure requiring supplemental oxygen or advanced airway support, and had at least one of the following: (1) clinical suspicion of lower respiratory tract infection based on clinical, biochemical, or radiological findings, (2) sepsis of unknown origin, and (3) concern from an intensive care physician regarding inflammatory pathology. Patients with a suspected or confirmed containment level three organism were excluded. The outcome was performance characteristics of the metagenomic test compared with routine diagnostic testing, detection of additional pathogens by metagenomics, change in antimicrobial prescribing within 24 h of testing, and initiation of immunomodulation. FINDINGS: We processed 114 samples (1-5 per day) from 74 patients (39 [53%] female and 35 [47%] male). 107 (94%) of 114 samples passed quality control, of which 101 (94%) provided same-day preliminary results. Bacteria were detected in 45 (43%) of 104 tested specimens, fungal organisms in 17 (16%) of 104 tested specimens, and viruses in 28 (34%) of 83 tested specimens. Sensitivity in lower respiratory tract samples after 24 h was 97% (95% CI 87-100) for bacteria, 89% (65-99) for fungi, and 89% (71-98) for viruses, with only one false positive for bacteria. Metagenomics identified 42 pathogens not detected by other tests in 32 (30%) of 107 samples. Antimicrobial therapy was changed after metagenomic results from 30 (28%) of 107 samples: 22 (21%) were de-escalated and eight (7%) were escalated. Metagenomics contributed to the initiation of immunomodulation in 15 (20%) of 74 patients for a range of inflammatory conditions. Pathogens with clinical significance to local infection control or national public health were found in ten (14%) of 74 patients, including three invasive Group A streptococci, two parvovirus B19, and one each of HIV-1, measles virus, Mycobacterium tuberculosis, Neisseria meningitidis, and Mycoplasma pneumoniae. INTERPRETATION: Respiratory metagenomics for ICU patients showed good performance and turnaround time, and diverse clinical and public health benefits. This ability to inform both personalised patient therapy and infectious disease surveillance needs evaluation in multicentre studies. FUNDING: None.

Humans

Congenital infections and the nervous system.

Despite vaccines, new antimicrobials, and improved hygienic practices, congenital infections remain an important cause of death and long-term neurologic morbidity among infants world-wide. Important agents include Toxoplasma gondii, cytomegalovirus, Treponema pallidum, herpes simplex virus types 1 and 2, and rubella virus. In addition, several other agents, such as the varicella zoster virus, human parvovirus B19, and Borrelia burgdorferi, can potentially infect the fetus and cause adverse fetal outcomes. This article provides an overview of these infectious disorders and outlines current strategies for acute treatment and long-term management.

Cytomegalovirus Infections

In situ hybridisation: principles and applications.

In situ hybridisation (ISH) is based on the complementary pairing of labelled DNA or RNA probes with normal or abnormal nucleic acid sequences in intact chromosomes, cells or tissue sections. Compared with other molecular biology techniques applicable to anatomical pathology, ISH enjoys better rapport with histopathologists because of its similarity to immunohistochemistry. It has the unique advantage over other molecular biology techniques--largely based on probe hybridisation with nucleic acid extracted from homogenised tissue samples--of allowing localisation and visualisation of target nucleic acid sequences within morphologically identifiable cells or cellular structures. Probes for ISH may bear radioactive or non-radioactive labels. Isotopic probes (3H, 32P, 35S, 125I) are generally more sensitive than non-isotopic ones but are less stable, require longer processing times and stringent disposal methods. Numerous non-isotopic labels have been used; of these biotin and digoxigenin are the reporters of choice. Optimised non-isotopic systems of equivalent sensitivity to those which use radioactive-labelled probes have been described. In ISH, finding the optimal balance between good morphological preservation of cells and strong hybridisation signals is crucial. Tissue fixation and retention of cytoskeletal structures, unfortunately, impede diffusion of probes into tissues. ISH sensitivity is also influenced by inherent properties of the probe and hybridisation conditions. Although ISH is largely a research tool, it is already making strong inroads into diagnostic histopathology. It has been applied for the detection of various infective agents particularly CMV, HPV, HIV, JC virus, B19 parvovirus, HSV-1, EBV, HBV, hepatitis delta virus, Chlamydia trachomatis, salmonella and mycoplasma in tissue sections.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

Comparison of human fecal and serum parvo-like viruses.

Parvovirus-like particles found in the sera of two blood donors had the size and appearance on electron microscopy of a virus (B19) found in the serum of a blood donor by Cossart et al. (1975), and those of a virus found in the feces of a normal subject. Antibody to these viruses was detected by immune electron microscopy and immunoelectro-osmophoresis in the sera of 50 children aged 10 to 15 years. Of these, 36% had antibody to the fecal virus, 36% had antibody to B19, and 54% had antibody to the two other serum viruses. The results of these tests suggest that serologically the three serum viruses were similar to one another, but that the fecal virus was distinct. The two blood donors had nonspecific symptoms at the time of viremia. Both donors had developed immunoglobulin M antibody to the virus when tested 3.5 and 4.5 weeks later, but no viruses were detected in the feces or urine.

Adolescent