Fowl adenovirus serotype 4 (FAdV-4) infection induces inflammatory responses in chicken embryonic cardiac fibroblasts via PI3K/Akt and IκBα/NF-κB signaling pathways.

Fowl adenovirus serotype 4 (FAdV-4) is the main pathogen of the acute infectious disease hepatitis-hydropericardium syndrome (HHS). Previous studies have focused on the mechanisms of FAdV-4 caused liver injury, while studies revealing potential mechanisms of inflammatory injury in FAdV-4-infected chicken cardiac cells remain scare. Here we found that FAdV-4 successfully infected chicken embryonic cardiac fibroblasts (CECF) cells in vitro and significantly upregulated production of inflammatory cytokines including IL-1ß, IL-6, IL-8, and TNF-α, suggesting induction of a strong inflammatory response. Mechanistically, FAdV-4 infection increased expression of phosphorylated Akt in a time-dependent manner, while phosphorylation of Akt and production of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α were greatly reduced in FAdV-4-infected CECF cells after treatment with LY294002, a potent inhibitor of PI3K, indicating that the inflammatory response induced by FAdV-4 infection is mediated by the PI3K/Akt signaling pathway. Furthermore, FAdV-4 infection increased expression of phosphorylated IκBα, a recognized indicator of NF-κB activation, and treatment with the BAY11-7082, a selective IκBα phosphorylation and NF-κB inhibitor, significantly reduced IκBα phosphorylation and inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) production in FAdV-4-infected CECF cells, suggesting a critical role of IκBα/NF-κB signaling in FAdV-4-induced inflammatory responses in CECF cells. Taken together, our results suggest that FAdV-4 infection induces inflammatory responses through activation of PI3K/Akt and IκBα/NF-κB signaling pathways in CECF cells. These results reveal potential mechanisms of inflammatory damage in chicken cardiac cells caused by FAdV-4 infection, which sheds new insight into clarification of the pathogenic mechanism of FAdV-4 infection and development of new strategies for HHS prevention and control.

Systems approach to design multi-epitopic peptide vaccine candidate against fowl adenovirus structural proteins for Gallus gallus domesticus.

Introduction: Fowl adenovirus (FAdV) is a significant pathogen in poultry, causing various diseases such as hepatitis-hydropericardium, inclusion body hepatitis, and gizzard erosion. Different serotypes of FAdV are associated with specific conditions, highlighting the need for targeted prevention strategies. Given the rising prevalence of FAdV-related diseases globally, effective vaccination and biosecurity measures are crucial. In this study, we explore the potential of structural proteins to design a multi-epitope vaccine targeting FAdV. Methods: We employed an in silico approach to design the multi-epitope vaccine. Essential viral structural proteins, including hexon, penton, and fiber protein, were selected as vaccine targets. T-cell and B-cell epitopes binding to MHC-I and MHC-II molecules were predicted using computational methods. Molecular docking studies were conducted to validate the interaction of the multi-epitope vaccine candidate with chicken Toll-like receptors 2 and 5. Results: Our in silico methodology successfully identified potential T-cell and B-cell epitopes within the selected viral structural proteins. Molecular docking studies revealed strong interactions between the multi-epitope vaccine candidate and chicken Toll-like receptors 2 and 5, indicating the structural integrity and immunogenic potential of the designed vaccine. Discussion: The designed multi-epitope vaccine presents a promising approach for combating FAdV infections in chickens. By targeting essential viral structural proteins, the vaccine is expected to induce a robust immunological response. The in silico methodology utilized in this study provides a rapid and cost-effective means of vaccine design, offering insights into potential vaccine candidates before experimental validation. Future studies should focus on in vitro and in vivo evaluations to further assess the efficacy and safety of the proposed vaccine.

Molecular characterisation of fowl adenovirus associated with hydropericardium hepatitis syndrome in broiler and layer breeders in Azerbaijan.

BACKGROUND: Fowl adenovirus-4 is a causative agent of hydropericardium hepatitis syndrome (HHS) in chickens and has been frequently reported from many countries. Fowl adenoviruses cause severe disease and mortality in broiler and layer breeders in Azerbaijan. Therefore, in this study, pathological lesions and the dissemination of fowl adenovirus-4 into the visceral organs of infected birds were investigated as well as molecular characterisation of detected strains. For this, liver, heart and spleen from 20 necropsied chickens originated from a broiler breeder flock and a layer breeder flock were embeded on the FTA cards and the samples were analysed for adenovirus-DNA by PCR and sequencing. RESULTS: The findings of necropsy in both broiler and layer breeder chickens were similar, and the liver was severely effected showing hepatitis, and the heart with hydropericardium lesions. The kidneys were swollen with haemorrhages and small white foci on the surface of the spleens were noted. Intestinal congestion and ecchymotic hemorrhages were also observed in some birds. Fowl adenovirus-4-DNA was detected by PCR in all collected organs of 20 birds. The sequence analysis revealed that fowl adenovirus-4 present in Azerbaijan and close similarity of the hexon genes of the adenoviruses existing in the Middle East, North America, far east and Indian subcontinent were determined by phylogenetic analysis. However, sequence diversity was detected from the adenovirus strains circulating in Europe, North and South America. CONCLUSIONS: This study indicates the impact of fowl adenovirus-4 on the poultry health and production, and improved disease control and prevention strategies are necessary to reduce the HHS disease in chickens in Azerbaijan.

Hypervirulent fowl adenovirus serotype 4 elicits early innate immune response and promotes virus-induced cellular autophagy in the spleen.

The recent emergence of hepatitis-hydropericardium syndrome caused by highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in significant economic losses to the poultry industry. However, the early innate immune response of immune organs within 24 hpi and the induction of autophagy in vivo after FAdV-4 infection have not been fully elucidated. In this study, 35-day-old specific pathogen-free (SPF) chickens were artificially infected with hypervirulent FAdV-4, which resulted in a mortality rate of up to 90%. The results showed that FAdV-4 infection rapidly triggered the innate immune response in vivo of chickens, with the spleen eliciting a stronger innate immune response than the thymus and bursa. During the early stage of viral infection within 24 hpi, the main receptors TLR3/7/21, MDA5, and cGAS were activated via the NF-κB and TBK1/IRF7-dependent signaling pathways, which up-regulated production of inflammatory cytokines and type I interferons. Additionally, the expression levels of the autophagy-related molecules LC3B, Beclin1, and ATG5 were significantly up-regulated at 24 hpi, while degradation of SQSTM1/p62 was observed, suggesting that FAdV-4 infection elicits a complete autophagy response in the spleen. Besides, the colocalization of Fiber2 and LC3B suggested that FAdV-4 infection induced autophagy which benefits FAdV-4 replication in vivo. This study provides new insights into the immunoregulation signal pathways of the early innate immunity in response to hypervirulent FAdV-4 infection in vivo within 24 hpi and the close relationship between viral replication and autophagy.

Biological features of fowl adenovirus serotype-4.

Fowl adenovirus serotype 4 (FAdV-4) is highly pathogenic to broilers aged 3 to 5 weeks and has caused considerable economic loss in the poultry industry worldwide. FAdV-4 is the causative agent of hydropericardium-hepatitis syndrome (HHS) or hydropericardium syndrome (HPS). The virus targets mainly the liver, and HPS symptoms are observed in infected chickens. This disease was first reported in Pakistan but has now spread worldwide, and over time, various deletions in the FAdV genome and mutations in its major structural proteins have been detected. This review provides detailed information about FAdV-4 genome organization, physiological features, epidemiology, coinfection with other viruses, and host immune suppression. Moreover, we investigated the role and functions of important structural proteins in FAdV-4 pathogenesis. Finally, the potential regulatory effects of FAdV-4 infection on ncRNAs are also discussed.

Rapid detection of pigeon adenovirus 2 using a TaqMan real-time PCR assay.

Pigeons infected with aviadenoviruses have been found worldwide. Recently, pigeon adenovirus 2 (PiAdV-2) has been widely distributed in racing pigeons in Germany. However, the epidemiology of this virus remains unclear due to the lack of a specific detection platform for PiAdV-2. In this study, we first detected PiAdV-2 positivity in racing pigeons (designated FJ21125 and FJ21128, which share 100% nucleotide identity with each other based on the fiber 2 gene) in Fujian, Southeast China. These genes shared 99.8% nucleotide identity with PiAdV-2 (GenBank No. NC_031501) but only 54.1% nucleotide identity with PiAdV-1 (GenBank No. NC024474). Then, the TaqMan-qPCR assay for the detection of PiAdV-2 was established based on fiber 2 gene characterization. The established assay had a correlation coefficient of 1.00, with an amplification efficiency of 99.0%. The minimum detection limit was 34.6 copies/µL. Only PiAdV-2 exhibited a positive fluorescent signal, and no signal was detected for other pathogens (including PiCV, FAdV-4, FAdV-8a, EDSV, PPMV-1, RVA and PiHV). The assay has good reproducibility, with a coefficient of variation less than 2.42% both intragroup and intergroup. The distributions of PiAdV-2 in fecal samples from YPDS (35 samples) and healthy (43 samples) racing pigeons from different geographical areas were investigated and were 37.14% (YPDS) and 20.93% (healthy), respectively. In summary, we developed a TaqMan-qPCR platform for the detection of PiAdV-2 infection with high sensitivity, specificity, and reproducibility. We confirmed the presence of PiAdV-2 in China, and our data suggested that there is no indication of a correlation between YPDS and PiAdV-2. This study provides more information on the pathogenesis mechanism and epidemiological surveillance of PiAdV-2.

Pathological and phylogenetic characterization of a rare fowl adenovirus (FAdV-8b) associated with inclusion body hepatitis in naturally infected Meleagris gallopavo.

Adenoviruses are a diverse group of viruses that can cause a variety of diseases in poultry, including respiratory and gastrointestinal infections. In turkeys (Meleagris gallopavo), adenoviruses commonly cause hemorrhagic enteritis and, rarely, inclusion body hepatitis. In this study, we investigated fowl adenoviruses (FAdVs) circulating in turkeys in Egypt. Following clinical examination of 500 birds, a portion of the hexon gene was amplified from four out of 50 samples from diseased birds (8%), and one amplicon that produced a strong band was selected for sequencing. Molecular and phylogenetic analysis revealed that the virus in that sample belonged to serotype FAdV-8b. Histopathological and immunohistochemical examinations of prepared tissue sections were performed to confirm the pathological findings. Diseased birds exhibited ruffled feathers, low body weight, a crouching posture, and diarrhea. Gross examination revealed petechial hemorrhage on the spleen, swollen pale liver, and congested intestine. Microscopic examination revealed the presence of eosinophilic and basophilic intranuclear inclusion bodies, nuclear pyknosis, and apoptotic bodies in the liver, congestion, hemorrhage, and fibrosis in the lungs, and desquamation of enterocytes. The presence of viral antigens in the liver, lungs, and intestine was confirmed by immunohistochemistry. To our knowledge, this is the first report of the characterization of an outbreak of inclusion body hepatitis in turkeys (hybrid converter breeds) due to FAdV-8b in Egypt. This finding raises an epidemiological alarm, necessitating further studies, including full-genome sequencing, to trace the virus's origin and genetic diversity.

A novel subunit vaccine based on Fiber1/2 knob domain provides full protection against fowl adenovirus serotype 4 and induces stronger immune responses than a Fiber2 subunit vaccine.

Outbreaks of hepatitis-hydropericardium syndrome (HHS) caused by fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry in China since 2015. However, commercially available vaccines against the FAdV-4 infection remain scarce. In our study, subunit vaccine candidates derived from the bacterially expressed recombinant Fiber1 knob domain and Fiber2 knob domain fusion protein (termed as Fiber1/2 knob subunit vaccine) and Fiber2 protein (termed as Fiber2 subunit vaccine) of the FAdV-4 SDSX strain were developed. Immunogenicity evaluation showed that the Fiber1/2 knob subunit vaccine induced the production of antibodies at 7 d postvaccination (dpv), earlier than the Fiber2 subunit vaccine. Moreover, the neutralizing antibody level of the Fiber1/2 subunit vaccine group was higher than the Fiber2 subunit vaccine group, showing significant differences at 14, 21, and 28 dpv. Immune protection test results revealed that both Fiber1/2 knob subunit and Fiber2 subunit vaccines could protect chickens from death against FAdV-4 challenge, although the weight of chickens in the Fiber1/2 knob subunit vaccine group decreased less. Furthermore, analysis of plasma Glutamic oxaloacetic transaminase (AST) and blood glutamic pyruvic transaminase (ALT) levels suggested that the Fiber1/2 subunit vaccine can significantly inhibit liver damage caused by FAdV-4 infection and is more effective in blocking the pathogenicity of FAdV-4 in target organs. In addition, the Fiber1/2 knob subunit vaccine further reduced the viral load in different tissues and virus shedding in chickens than the Fiber2 subunit vaccine. Overall, the Fiber1/2 knob subunit vaccine was more effective than the Fiber2 subunit vaccine. These findings lay the foundation for the development of more effective FAdV-4 subunit vaccines.

The Immune System-A Double-Edged Sword for Adenovirus-Based Therapies.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

PD-1 blockade immunotherapy as a successful rescue treatment for disseminated adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with Epstein‒Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy.

Determinants of antibiotic prescription in children with adenovirus respiratory tract infections.

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4-7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42-103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01-1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25-11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00-1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65-100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41-2.89; p = 0.009) even when adjusted for CrP values.    Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: • Adenovirus infection is a common cause of fever and respiratory tract infections in children. • Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics.

Clinical manifestations, prognostic factors, and outcomes of adenovirus pneumonia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

Fecal leukocyte frequency in children with acute viral gastroenteritis: a single-center experience.

OBJECTIVE: Our objective was to determine the frequency of rotavirus, adenovirus, and rota-adenovirus co-infections and investigate the fecal leukocyte rate associated with these infections in patients with gastroenteritis. METHODS: This is a retrospective study. We identified patients who were admitted to the pediatric emergency department with acute gastroenteritis and had their stool samples tested for rotavirus and/or adenovirus antigens. Among them, we determined the individuals who underwent stool microscopy tests on the same day and recorded their results. RESULTS: A total of 1,577 patients who underwent testing for rotavirus and/or adenovirus antigens in their stool samples were identified. Among these patients, 583 individuals had concurrent fecal microscopy results. The prevalence of solely rotavirus antigen positivity was 16.4%, solely adenovirus antigen positivity was 2.9%, and rota-adenovirus co-infections were detected in 1.8% of the children. The fecal leukocyte rates in children infected with rotavirus, adenovirus, and rota-adenovirus co-infections were 4.8, 13.3, and 88.9%, respectively. CONCLUSION: The presence of fecal leukocytes was detected at a high rate in cases of viral gastroenteritis, especially in rota-adenovirus co-infections. Therefore, clinicians should not consider only bacterial pathogens in the presence of fecal leukocytes.

Diagnostic value of cytokines in severe childhood Mycoplasma pneumoniae pneumonia combined with Adenovirus infection.

BACKGROUND: To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV). METHODS: The study population consisted of 201 children with MPP, and they were grouped according to whether they were coinfected with ADV infection and critically ill. Additionally, comparative analyses were performed. The diagnostic value of different indicators and combined indicators for SMPP combined with ADV was assessed using ROC curves. RESULTS: There was no difference between group A1 and group A2, group B1 and group B2 in terms of age, gender, duration of hospitalisation and fever. The levels of calcitoninogen(PCT), lactate dehydrogenase concentration(LDH), interleukin(IL)-6, IL-8, IL-10, IL-4, IL-12P70, and IFN-γ in group A were higher than group B. The severe group (A1, B1) was significantly higher than the mild group (A2, B2) in terms of D-dimer, CRP, PCT, LDH, IL-6, IL-8, IL-10, IL-17a and number of patients with pleural effusion, solid lung changes. Among the individual indexes of D-dimer, CRP, N%,LDH, and PCT, the AUC of the combined test was 0.977, which was higher than that of the individual indicators. Among IL-6, IL-8, IL-10, and IL-17a, the AUC of the combined assay was 0.802, which was higher than that of the individual indicators. CONCLUSION: MP combined with ADV infection was associated with increased expression levels of IL-6, IL-8, IL-10, IL-4, IL-12P70, IFN-γ, and LDH. IL-6, IL-8, IL-10, IL-17a, LDH, PCT, CRP, and D-dimer could be used as predictors of SMPP and the combined test can improve the diagnostic value.

Concurrent Histomonas meleagridis and Hemorrhagic Enteritis Virus Infection in a Turkey Flock with Recurrent History of Blackhead Disease.

Intestinal health is one of the key factors required for the growth and production of turkeys. Histomoniasis (blackhead disease), caused by a protozoan parasite, Histomonas meleagridis, is a reemerging threat to the turkey industry. Increased incidences of histomoniasis have been reported in recent years due to withdrawal of antihistomonas treatments. H. meleagridis affects ceca and causes cecal inflammation and necrosis. H. meleagridis migrates from ceca to the liver and causes liver necrosis, resulting in high mortalities. Ironically, field outbreaks of histomoniasis are not always associated with high mortalities, while low mortalities have also been documented. There are several exacerbating factors associated with high mortality rates in histomoniasis outbreaks, with concurrent infection being one of them. Recurrent histomoniasis outbreaks in a newly constructed barn were documented, and concurrent infection of H. meleagridis and hemorrhagic enteritis virus was confirmed. Currently, neither commercial vaccines nor prophylactic or therapeutic solutions are available to combat histomoniasis. However, there are treatments, vaccines, and solutions to minimize or prevent concurrent infections in turkeys. In addition to implementing biosecurity measures, measures to prevent concurrent infections are critical steps that the turkey industry can follow to reduce mortality rates and minimize the production and economic losses associated with histomoniasis outbreaks.

Infección simultánea por Histomonas meleagridis y el virus de la enteritis hemorrágica en una parvada de pavos con antecedentes recurrentes de enfermedad de la cabeza negra. La salud intestinal es uno de los factores clave necesarios para el crecimiento y producción de los pavos. La histomoniasis (enfermedad de la cabeza negra), causada por un parásito protozoario, Histomonas meleagridis, es una amenaza reemergente para la industria del pavo. En los últimos años se ha informado de un aumento de la incidencia de histomoniasis debido al retiro de los tratamientos con antihistomonas. Histomonas meleagridis afecta los ciegos y causa inflamación y necrosis cecal. Histomonas meleagridis migra desde los ciegos al hígado y causa necrosis hepática, lo que resulta en una alta mortalidad. Irónicamente, los brotes de histomoniasis en el campo no siempre se asocian con una mortalidad elevada, aunque también se han documentado mortalidades bajas. Hay varios factores exacerbantes asociados con altas tasas de mortalidad en los brotes de histomoniasis, siendo la infección concurrente uno de ellos. Se documentaron brotes recurrentes de histomoniasis en un alojamiento avícola recién construido y se confirmó la infección concurrente de H. meleagridis y el virus de la enteritis hemorrágica. Actualmente no se dis-pone de vacunas comerciales ni soluciones profilácticas o terapéuticas para combatir la histomoniasis. Sin embargo, existen tratamientos, vacunas y soluciones para minimizar o prevenir infecciones concurrentes en los pavos. Además de implementar medidas de bioseguridad, las medidas para prevenir infecciones concurrentes son pasos críticos que la industria del pavo puede seguir para reducir las tasas de mortalidad y minimizar las pérdidas económicas y de producción asociadas con los brotes de histomoniasis.

Identification, pathogenicity and molecular characterization of a novel fowl adenovirus 8b strain.

Since 2012, there has been a noticeable upward trend in the global incidence of inclusion body hepatitis (IBH) cases, leading to substantial economic losses in the poultry industry. In response to this trend, the current study aimed to investigate the phylogenetic information, genetic mutations, and pathogenicity of the highly pathogenic fowl adenovirus (FAdV) strain HN1472, which was isolated from liver samples obtained from a laying flock affected by IBH. This investigation was carried out using 1-day-old specific pathogen-free (SPF) chickens. Recombination and phylogenetic analyses confirmed that HN1472 is a recombinant strain derived from FAdV-8a and FAdV-8b, and exhibited significant genetic divergence in the hexon, fiber, and ORF19 genes. Notably, the phylogenetic analysis identified recombination events in these regions. Furthermore, animal experiments revealed that HN1472 is a highly pathogenic isolate, causing 80% mortality and manifesting clinical signs of IBH in SPF chickens. Furthermore, the recombinant FAdV serotype 8b (FAdV-8b) was found to be widely distributed in various tissues, with a higher concentration in the livers and gizzard tissue at 3 d postchallenge (dpc). Collectively, these findings contribute to our current understanding of the factors influencing the pathogenicity and genetic diversity of FAdV serotype 8b (FAdV-8b) in China.

Pyrococcus furiosus argonaute combined with loop-mediated isothermal amplification for rapid, ultrasensitive, and visual detection of fowl adenovirus serotype 4.

Since 2015, an outbreak of an infectious disease in broilers caused by fowl adenovirus serotype 4 (FAdV-4) has occurred in China, resulting in substantial economic losses. Rapid, accurate, and specific detection are significant in the prevention and control of FAdV-4. In this study, an FAdV-4 detection method combining loop-mediated isothermal amplification (LAMP) and Pyrococcus furiosus Argonaute (PfAgo) was established. Specific primers, guide DNAs (gDNAs), and molecular beacons were designed to target a conserved region of the FAdV-4 hexon gene. After optimizing the reaction conditions, the minimum detection of this assay could reach 5 copies. It only amplified FAdV-4, and there was no cross-reactivity with other pathogens. The assay took about only 50 min, and the results could be visualized with the naked eye under ultraviolet or blue light, getting rid of specialized instruments. This novel LAMP-PfAgo assay was validated by using 20 clinical samples and the results were identical to gold-standard real-time polymerase chain reaction method. In summary, the LAMP-PfAgo assay established in the paper provides a rapid, reliable, convenient, ultra-sensitive and highly specific tool for the on-site detection and clinical diagnosis of FAdV-4.

Severe adenovirus infection outbreak in Colombia: Experience from a tertiary pediatric hospital in 2022. / Brote de adenovirus grave en Colombia: experiencia de un hospital pediátrico de tercer nivel en 2022

Introduction. During the SARS-CoV-2 pandemic, many countries experienced decreased respiratory virus circulation, followed by an out-of-season outbreak. In a pediatric hospital in Colombia, we observed a surge in severe adenovirus infections, leading to concerns about the impact of eased public health restrictions and immune debt in children under five years old. Objective. To describe the clinical characteristics of patients with severe adenovirus infection in a pediatric hospital in Colombia. Materials and methods. We reviewed the data of 227 patients with severe adenovirus infection at the Fundación Hospital Pediátrico La Misericordia. Results. A total of 196 patients were included in this study. The median age was two years, and 62% were male. Adenoviruses were isolated from all patients' samples. Ninetyseven percent were admitted to the pediatric intensive care unit, 94% required respiratory support, and the in-hospital lethality rate was 11%. Conclusion. In 2022, there was an outbreak of severe adenovirus infections, affecting mainly children under five years of age, with higher-than-usual mortality.

Introducción. Durante la pandemia por SARS-CoV-2, muchos países evidenciaron una disminución en la circulación de virus respiratorios, seguida por un brote fuera de la temporada esperada. En un hospital de Colombia, se observó un aumento en los casos de infección grave por adenovirus, lo cual generó preocupación sobre el impacto que tuvo la disminución de los cuidados establecidos durante pandemia y la posible deuda inmunológica en niños menores de cinco años. Objetivo. Describir las características clínicas de los pacientes con infección grave por adenovirus en un hospital pediátrico de Colombia. Materiales y métodos. Se revisaron 227 pacientes con infección grave por adenovirus en la Fundación Hospital Pediátrico La Misericordia, desde el 1° de enero hasta el 31 de diciembre de 2022. Resultados. El estudio incluyó 196 casos. La edad media de los pacientes fue de dos años y el 62 % eran de sexo masculino. Los adenovirus se aislaron a partir de las muestras de todos los pacientes. El 97 % de los pacientes ingresó a la unidad de cuidados intensivos, el 94 % requirió soporte ventilatorio y la tasa de mortalidad fue del 11 %. Conclusiones. En el 2022 hubo un brote de adenovirus que afectó principalmente a los niños menores de cinco años, con una mortalidad mayor a lo reportado con anterioridad en Colombia.

Epidemiology of Adenovirus Infection in Hospitalized Children in the United States From 1997 to 2019.

OBJECTIVE: The study aimed to explore the prevalence, clinical features, resource utilization, temporal trends and outcomes associated with adenoviral infections in hospitalized children. METHODS: A retrospective analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997 to 2019 was performed. Children 29 days to 17 years of age with adenoviral infection were selected. Chi-square, Kruskal-Wallis tests, linear trend analysis and multivariable analysis were used for data analysis. RESULTS: A total of 40,135 children under 18 years of age with adenoviral infection were discharged in the United States with an overall prevalence of 18.9 per 10,000 discharges and 6.9 children per 100,000 population. By linear trend analysis, the hospitalization rate has significantly increased with the highest prevalence in 2019. Adenoviral infection was more prevalent in Black children, in winter months, in the Midwest region, in children with government insurance and in the lowest income quartile. The majority (85%) of adenovirus-related hospitalizations occurred under 6 years of age. Mechanical ventilation, extracorporeal membrane oxygenation support, acute kidney injury and liver failure were documented in 11.9%, 0.4%, 2.7% and 0.4%, respectively. The overall case fatality rate was 1.4%, which decreased from 1997 to 2019 ( P < 0.05). By regression analysis, an increased mortality rate was associated with the need for mechanical ventilation, the presence of complex chronic conditions, immune deficiency, central nervous system infection and pneumonia/bronchiolitis. CONCLUSIONS: Most human adenovirus infections occur in children under 6 years of age and cause mild illness. Human adenovirus can lead to serious illness in children with complex chronic conditions and immune deficiency conditions.