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Veterinary Pathology May 2024Novel goose parvovirus (NGPV) is continuously threatening the global duck industry, as it causes short beak and dwarfism syndrome among different duck breeds. In this...
Novel goose parvovirus (NGPV) is continuously threatening the global duck industry, as it causes short beak and dwarfism syndrome among different duck breeds. In this study, we investigated the viral pathogenesis in the tongue of affected ducks, as a new approach for deeper understanding of the syndrome. Seventy-three, 14- to 60-day-old commercial Pekin ducks were clinically examined. Thirty tissue pools of intestine and tongue (15 per tissue) were submitted for molecular identification. Clinical signs in the examined ducks were suggestive of parvovirus infection. All examined ducks had short beaks. Necrotic, swollen, and congested protruding tongues were recorded in adult ducks (37/73, 51%). Tongue protrusion without any marked congestion or swelling was observed in 20-day-old ducklings (13/73, 18%), and no tongue protrusion was observed in 15-day-old ducklings (23/73, 32%). Microscopically, the protruding tongues of adult ducks showed necrosis of the superficial epithelial layer with vacuolar degeneration. Glossitis was present in the nonprotruding tongues of young ducks, which was characterized by multifocal lymphoplasmacytic aggregates and edema in the propria submucosa. Immunohistochemical examination displayed parvovirus immunolabeling, mainly in the tongue propria submucosa. Based on polymerase chain reaction, goose parvovirus was detected in 9 out of 15 tongue sample pools (60%). Next-generation sequencing confirmed the presence of a variant goose parvovirus that is globally named NGPV and closely related to Chinese NGPV isolates. Novel insights are being gained from the study of NGPV pathogenesis in the tongue based on molecular and immunohistochemical identification.
PubMed: 38712876
DOI: 10.1177/03009858241249108 -
BioRxiv : the Preprint Server For... Mar 2024The initial objective of this study was to shed light on the evolution of small DNA tumor viruses by analyzing assemblies of publicly available deep sequencing...
The initial objective of this study was to shed light on the evolution of small DNA tumor viruses by analyzing assemblies of publicly available deep sequencing datasets. The survey generated a searchable database of contig snapshots representing more than 100,000 Sequence Read Archive records. Using modern structure-aware search tools, we iteratively broadened the search to include an increasingly wide range of other virus families. The analysis revealed a surprisingly diverse range of chimeras involving different virus groups. In some instances, genes resembling known DNA-replication modules or known virion protein operons were paired with unrecognizable sequences that structural predictions suggest may represent previously unknown replicases and novel virion architectures. Discrete clades of an emerging group called adintoviruses were discovered in datasets representing humans and other primates. As a proof of concept, we show that the contig database is also useful for discovering RNA viruses and candidate archaeal phages. The ancillary searches revealed additional examples of chimerization between different virus groups. The observations support a gene-centric taxonomic framework that should be useful for future virus-hunting efforts.
PubMed: 38712252
DOI: 10.1101/2024.03.25.586562 -
The Lancet. Haematology Jun 2024Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell...
BACKGROUND
Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years.
METHODS
In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sβ zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing.
FINDINGS
We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 10 cells per L to 3·6 [2·2] × 10 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths.
INTERPRETATION
Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa.
FUNDING
US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation.
Topics: Humans; Hydroxyurea; Anemia, Sickle Cell; Child, Preschool; Child; Male; Female; Africa South of the Sahara; Follow-Up Studies; Infant; Antisickling Agents; Treatment Outcome; Dose-Response Relationship, Drug
PubMed: 38701812
DOI: 10.1016/S2352-3026(24)00078-4 -
Tierarztliche Praxis. Ausgabe K,... Apr 2024For detection of infectious diseases, several point-of-care (POC) tests are on the market in addition to methods performed in commercial laboratories. These POC tests...
For detection of infectious diseases, several point-of-care (POC) tests are on the market in addition to methods performed in commercial laboratories. These POC tests are based on enzyme-linked immunosorbent assay (ELISA) or other immunochromatographic technologies and present results within few minutes in veterinary practice. This article gives an overview of the utility of numerous POC tests of different manufacturers for detection of parvovirus antigen in feces, antigen in blood as well as antibodies against (.) , (.) spp., (.) spp., (.) spp. and (.) in blood (single or in different combinations). Sensitivity and specificity of these tests are important for their usefulness in veterinary practice. Furthermore, presence of antibodies or detection of antigen has to correlate with the presence of clinical signs. POC tests for detection of canine parvovirus antigen have a very high specificity, the sensitivity of all evaluated POC tests, however, is very low. POC tests for detection of antigen have a very high sensitivity and specificity. As they detect antigen from the uterus of female adult parasites, test results are negative when only very few female or only male adults are present. POC tests for detection of antibodies against only indicate contact with spp. and do not prove clinical Lyme disease, as the infection only extremely rarely causes clinical signs. POC tests for detection of antibodies against are also not suitable for diagnosis of clinical anaplasmosis. Infections with only lead to clinical disease in very rare cases and in these, clinical signs occur before the development of antibodies. POC tests for detection of antibodies against have a very high sensitivity as well as specificity. POC tests for detection of antibodies against and species (spp.) show a very high specificity and a high sensitivity. However, spp. antibody-positive results may occur following vaccination, as the POC tests cannot distinguish between field and vaccination strains.
Topics: Animals; Dogs; Dog Diseases; Enzyme-Linked Immunosorbent Assay; Point-of-Care Systems; Sensitivity and Specificity
PubMed: 38701805
DOI: 10.1055/a-2289-1927 -
Prenatal Diagnosis Apr 2024The objective of our study was to evaluate the long-term outcome of children born from a pregnancy complicated by idiopathic polyhydramnios. The secondary objective was...
OBJECTIVES
The objective of our study was to evaluate the long-term outcome of children born from a pregnancy complicated by idiopathic polyhydramnios. The secondary objective was to investigate factors associated with adverse outcomes.
METHODS
We conducted a retrospective study in two prenatal diagnosis centers between January 1, 2009 and December 31, 2020. Inclusion criteria were pregnancies with a diagnosis of idiopathic polyhydramnios, defined by a deepest pocket greater than 8 cm, no detectable abnormality at ultrasound and a negative amniotic fluid assessment including karyotype, chromosomal microarray, biochemical assays (electrolytes and digestive enzymes), and viruses (parvovirus B19 and cytomegalovirus). One-year outcomes of these children were collected. The primary endpoint was adverse postnatal outcome, defined by at least one of the following criteria: stillbirth, neonatal death, or serious and incurable condition diagnosed in the first year of life.
RESULTS
Of the 245 women referred for isolated polyhydramnios, 73 were diagnosed with idiopathic polyhydramnios after prenatal investigations. The mean age at follow-up of children was 28 months (95% CI 20-36). An adverse outcome occurred in 25% of cases (18/73), with one stillbirth, two neonatal deaths, and 15 severe conditions diagnosed postnatally, including a rate of monogenic disorders of 8.2% (6/73). Pediatric follow-up was normal for 75% of the children (55/73), including a rate of 9% (5/55) of curable conditions. Repeated amnioreduction was independently associated with an adverse outcome.
CONCLUSION
Pregnant women with polyhydramnios should be informed of the increased risk of 25% of perinatal mortality and serious conditions diagnosed after birth.
PubMed: 38682787
DOI: 10.1002/pd.6573 -
EFSA Journal. European Food Safety... Apr 2024Two alternative methods for producing compost in a tunnel, from certain category (Cat.) 3 animal by-products (ABP) and other non-ABP material, were assessed. The first...
Two alternative methods for producing compost in a tunnel, from certain category (Cat.) 3 animal by-products (ABP) and other non-ABP material, were assessed. The first method proposed a minimum temperature of 55°C for 72 h and the second 60°C for 48 h, both with a maximum particle size of 200 mm. The assessment of the Panel on Biological Hazards (BIOHAZ) exclusively focused on Cat. 3 ABP materials (catering waste and processed foodstuffs of animal origin no longer intended for human consumption). The proposed composting processes were evaluated for their efficacy to achieve a reduction of at least 5 log of and Senftenberg (775W, HS negative) and at least 3 log of relevant thermoresistant viruses. The applicant provided a list of biological hazards that may enter the composting process and selected parvoviruses as the indicator of the thermoresistant viruses. The evidence provided by the applicant included: (a) literature data on thermal inactivation of biological hazards; (b) results from validation studies on the reduction of , Senftenberg 775W HS negative and canine parvovirus carried out in composting plants across Europe; (c) and experimental data from direct measurements of reduction of infectivity of murine parvovirus in compost material applying the time/temperature conditions of the two alternative methods. The evidence provided showed the capacity of the proposed alternative methods to reduce and Senftenberg 775W HS negative by at least 5 log, and parvoviruses by at least 3 log. The BIOHAZ Panel concluded that the two alternative methods under assessment can be considered to be equivalent to the processing method currently approved in the Commission Regulation (EU) No 142/2011.
PubMed: 38681740
DOI: 10.2903/j.efsa.2024.8745 -
Seminars in Fetal & Neonatal Medicine Feb 2024Congenital infections are a common but often underrecognized cause of fetal brain abnormalities, as well as fetal-neonatal morbidity and mortality, that should be... (Review)
Review
Congenital infections are a common but often underrecognized cause of fetal brain abnormalities, as well as fetal-neonatal morbidity and mortality, that should be considered by all healthcare professionals providing neurological care to fetuses and newborns. Maternal infection with various pathogens (cytomegalovirus, Toxoplasmosis, Rubella virus, Parvovirus B19, lymphocytic choriomeningitis virus, syphilis, Zika virus, varicella zoster virus) during pregnancy can be transmitted to the developing fetus, which can cause multisystem dysfunction and destructive or malformative central nervous system lesions. These can be recognized on fetal and neonatal imaging, including ultrasound and MRI. Imaging and clinical features often overlap, but some distinguishing features can help identify specific pathogens and guide subsequent testing strategies. Some pathogens can be specifically treated, and others can be managed with targeted interventions or symptomatic therapy based on expected complications. Neurological and neurodevelopmental complications related to congenital infections vary widely and are likely driven by a combination of pathophysiologic factors, alone or in combination. These include direct invasion of the fetal central nervous system by pathogens, inflammation of the maternal-placental-fetal triad in response to infection, and long-term effects of immunogenic and epigenetic changes in the fetus in response to maternal-fetal infection. Congenital infections and their neurodevelopmental impacts should be seen as an issue of public health policy, given that infection and the associated complications disproportionately affect woman and children from low- and middle-income countries and those with lower socio-economic status in high-income countries. Congenital infections may be preventable and treatable, which can improve long-term neurodevelopmental outcomes in children.
Topics: Humans; Pregnancy; Female; Pregnancy Complications, Infectious; Infant, Newborn; Infectious Disease Transmission, Vertical; Brain Diseases
PubMed: 38677956
DOI: 10.1016/j.siny.2024.101526 -
Viruses Apr 2024Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the...
Chimeric Porcine Parvovirus VP2 Virus-like Particles with Epitopes of South African Serotype 2 Foot-and-Mouth Disease Virus Elicits Specific Humoral and Cellular Responses in Mice.
Southern Africa Territories 2 (SAT2) foot-and-mouth disease (FMD) has crossed long-standing regional boundaries in recent years and entered the Middle East. However, the existing vaccines offer poor cross-protection against the circulating strains in the field. Therefore, there is an urgent need for an alternative design approach for vaccines in anticipation of a pandemic of SAT2 Foot-and-mouth disease virus (FMDV). The porcine parvovirus (PPV) VP2 protein can embed exogenous epitopes into the four loops on its surface, assemble into virus-like particles (VLPs), and induce antibodies and cytokines to PPV and the exogenous epitope. In this study, chimeric porcine parvovirus VP2 VLPs (chimeric PPV-SAT2-VLPs) expressing the T-and/or B-cell epitopes of the structural protein VP1 of FMDV SAT2 were produced using the recombinant pFastBac™ Dual vector of baculoviruses in Sf9 and HF cells We used the Bac-to-Bac system to construct the recombinant baculoviruses. The VP2-VLP--SAT2 chimeras displayed chimeric T-cell epitope (amino acids 21-40 of VP1) and/or the B-cell epitope (amino acids 135-174) of SAT FMDV VP1 by substitution of the corresponding regions at the N terminus (amino acids 2-23) and/or loop 2 and/or loop 4 of the PPV VP2 protein, respectively. In mice, the chimeric PPV-SAT2-VLPs induced specific antibodies against PPV and the VP1 protein of SAT2 FMDV. The VP2-VLP-SAT2 chimeras induced specific antibodies to PPV and the VP1 protein specific epitopes of FMDV SAT2. In this study, as a proof-of-concept, successfully generated chimeric PPV-VP2 VLPs expressing epitopes of the structural protein VP1 of FMDV SAT2 that has a potential to prevent FMDV SAT2 and PPV infection in pigs.
Topics: Animals; Foot-and-Mouth Disease Virus; Mice; Foot-and-Mouth Disease; Capsid Proteins; Parvovirus, Porcine; Antibodies, Viral; Viral Vaccines; Vaccines, Virus-Like Particle; Swine; Immunity, Humoral; Immunity, Cellular; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; Serogroup; Mice, Inbred BALB C; Female; Epitopes; Sf9 Cells; Antibodies, Neutralizing; Antigens, Viral
PubMed: 38675963
DOI: 10.3390/v16040621 -
Scientific Reports Apr 2024Parvovirus B19V (B19V) infection during pregnancy can be complicated by potentially life-threatening fetal hydrops, which can be managed by intrauterine transfusion...
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.
Topics: Humans; Netherlands; COVID-19; Parvovirus B19, Human; Female; Pregnancy; Hydrops Fetalis; Incidence; Parvoviridae Infections; Pregnancy Complications, Infectious; SARS-CoV-2; Pandemics; Erythema Infectiosum; Blood Transfusion, Intrauterine; Adult
PubMed: 38671058
DOI: 10.1038/s41598-024-59582-7 -
Frontiers in Immunology 2024Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and... (Review)
Review
Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and skeletal muscles; diagnostic criteria of JDM include an unforeseeable mixture of clinical features, while treatment modalities commonly require corticosteroids or immunosuppressant agents. Although the pathogenesis of JDM is not completely understood, several infectious triggers have been linked to its priming via anecdotal reports related to children. Pediatric cases of recent-onset JDM have been temporally associated to an infectious disease by the power of increased titers of circulating antibodies to a putative infectious agent, including parasites, and/or detectable viral RNA or bacterial DNA. With this narrative review we offer an update about JDM association with a host of infections, namely parvovirus B19, Epstein-Barr virus, Coxsackie virus, human immune deficiency virus, severe acute respiratory syndrome coronavirus 2, and , as resulting from the medical literature. Few are the evidence-proved results addressing JDM as an unambiguous post-infectious disorder and available data specifically related to children are poor, highlighting the need of further research into the exploration between environmental cut-out factors and JDM.
Topics: Humans; Dermatomyositis; Child; COVID-19; SARS-CoV-2
PubMed: 38660309
DOI: 10.3389/fimmu.2024.1377952