Clinical and inflammatory response to antiviral treatments in dogs with parvoviral enteritis.

BACKGROUND: Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival. OBJECTIVES: This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE. METHODS: Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM). RESULTS: Compared to the healthy control, the tumor necrosis factor-α, interleukin-1ß, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high (p < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven. CONCLUSIONS: Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE.

Algorithm for laboratory diagnostics of parvoviral infection in risk groups.

Parvovirus infection (PVI) is widespread, characterized by airborne, bloodborne and vertical transmission routes. Parvovirus B19 (PVB19) exhibits tropism to erythropoietic cells. According to the increased likelihood principle of PVB19 infection and the severity of the consequences, immunocompromised individuals, especially those with hematological manifestations of diseases, are in increased risk group. Based on the own research results and analysis of the published data, we have proposed specific algorithms for PVI laboratory testing in individual risk groups, taking into account the peculiarities of the development and infection manifestation in each group: in HIV-infected patients, in oncohematological patients with to whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been prescribed (blood and bone marrow recipients), as well as in patients with chronic anemia of parasitic etiology. For each group, the main clinical or laboratory marker, treatment procedure, or patient physiological parameters have been determined, based on which it was recommended to test for PVI. For HIV-infected patients, the main criterion for PVI testing is persistent anemia. For oncohematological patients, the basis for PVI testing is allo-HSCT procedure, which is planned or performed for this particular patient. For malaria patients, the patient's age was considered as major criterion, since in malaria and PVI coinfected young children can lead to a fatal outcome. The proposed PVI diagnostics algorithms usein risk groups can help to predict the severe course of underlying disease associated with PVB19 infection, and timely correct the therapy used.

Parvovirus B19-induced severe anemia in heart transplant recipient: A case report.

RATIONALE: Human parvovirus B19 (B19V) is a non-enveloped single-stranded DNA virus associated with a variety of human diseases. Reports of B19V infection after cardiac transplantation are relatively rare. PATIENT CONCERNS: We report a case of a 48-year-old women who underwent orthotopic heart transplant for dilated cardiomyopathy. She developed an anemia after cardiac transplantation. Anemia was most severe 2 months after surgery, with a decrease in reticulocyte count. Serological DNA test for parvovirus B19V was performed and the result was positive. DIAGNOSES: B19V infection. INTERVENTIONS AND OUTCOMES: Intravenous immunoglobulin administration resulted in a resolution of the anemia. The patient's blood test results showed a normal hemoglobin and reticulocyte count 1 year after surgery. LESSONS: Patients with parvovirus B19V infection may develop severe anemia after heart transplantation. The diagnosis mainly relies on viral DNA detection. Intravenous immunoglobulin is an effective treatment for viral infection.

Effects of astragalus polysaccharide on intestinal inflammatory damage in goslings infected with gosling plague.

1. This study explored the effects of Astragalus membranaceus polysaccharide (APS) on intestinal inflammatory damage of goslings infected with parvovirus ('gosling plague').2. A total of 90 healthy goslings were randomly divided into three groups; control, infected or APS treated, respectively. Goslings in the infection and APS treatment groups were inoculated with 0.3 ml allantoic fluid containing goose parvovirus (ELD50 = 1 × 103/0.3 ml) by intramuscular injection and the control group were injected with saline (0.3 ml) twice a day for 15 days.3. Blood serum and the jejunum were collected at 5, 10 and 15 days after the start of the experiment to detect the activities of SOD and GSH-Px, levels of MDA, sIgA, IL-1ß, IL-6 and TNF-α, the mRNA expression of IL-1ß, IL-6, LITAF, NF-κB, COX-2 and PGE2, pathological damage in the jejunum and serum IgG, IgM, C3, C4, IFN-γ levels.4. After APS treatment, SOD and GSH-Px activities increased, MDA content decreased; sIgA, IL-1ß, IL-6 and TNF-α protein content, and IL-1ß, IL-6, LITAF, NF-κB, COX-2 and PGE2 mRNA expression decreased in the jejunal tissue, serum IgG, IgM, C3, C4, IFN-γ significantly increased and pathological damage of jejunum significantly improved.5. In conclusion, APS reduced intestinal inflammatory damage in goslings infected with parvovirus by improving the immune and antioxidant functions of goslings.

Ferulic acid isolated from propolis inhibits porcine parvovirus replication potentially through Bid-mediate apoptosis.

Propolis from honeybee hives, which is a traditional Chinese medicine, is widely used in veterinary clinics. Many compounds have been identified and isolated from propolis. Ferulic acid (FA), one of the propolis components, previous studies have proven that it has antiviral effects. To study the mechanism of FA antiviral effects, experiments such as immunofluorescence, quantitative real-time PCR and immunoblotting were introduced. In porcine kidney (PK-15) cells, PPV infection induced the expression of the proapoptotic genes Bid, Bad, Bim and Bak, disrupted mitochondrial membrane potential, promoted mitochondria-mediated, caspase-dependent apoptotic signaling and induced apoptosis. Furthermore, the infected PK-15 cells had increased intracellular reactive oxygen species (ROS) generation. FA treatment, however, reversed these effects and increased cell viability. FA treatment also significantly decreased the PPV-induced expression of Bid, Cyt-c and Apaf-1, suggesting that ROS were involved in the activation of the mitochondria-mediated apoptosis pathway. This in vitro study showed that the antiviral activity of FA was probably associated with inhibiting the replication of PPV by blocking proapoptotic factors such as Bid, Bcl-2 and Mcl-1, and attenuating the mitochondria-mediated response by inhibiting the activation of the Bid-related signaling pathway. Pharmacological inhibitors inhibited PPV-induced apoptosis by blocking Bid, and also suppressed the expression of Caspase family proteins in ppv-induced apoptosis. Taken together, our results suggested that PPV induced PK-15 cell apoptosis via activation of Bid and Bid-related signaling pathways and that the mitochondria act as the mediators of these pathways. FA effectively and extensively attenuated this PPV action, and thus is a potential antiviral agent against PPV.

Infecção por parvovírus B19 em receptores de transplante renal: série de caso / Parvovirus B19 infection in kidney transplant recipients: a case series

Os receptores de transplante renal são mais suscetíveis a infecções, entre elas o parvovírus B19, que pode ser transmitido por via respiratória, adquirido por meio do enxerto ou por reativação de infecção latente. A anemia normocítica normocrômica, com diminuição dos reticulócitos e resistência ao tratamento com eritropoietina, é a principal forma de apresentação da infecção por parvovírus B19 em transplante renal. O diagnóstico requer alto índice de suspeição clínica e realização de testes diagnósticos selecionados. Tratamento com imunoglobulina e suspensão dos imunossupressores durante a infecção mostraram-se eficazes. Os autores relatam sua experiência com cinco casos de infecção por parvovírus B19 em receptores de transplante renal de um hospital universitário. Os aspectos clínicos, diagnósticos e terapêuticos são revistos.

Kidney transplant recipients are more susceptible to infections, including by parvovirus B19, spread through the respiratory tract, acquired through the graft or reactivation of latent infection. Normocytic normochromic anemia, with decreased reticulocytes and resistance to erythropoietin treatment, is the most common presentation of Parvovirus B19 infection in renal transplant. Diagnosis requires a higher clinical suspicion and the performance of selected diagnostic tests. Treatment with immunoglobulin and suspension of immunosuppressive therapy during the infection may be effective. The authors report five cases of PB19 infection in kidney transplant patients at a hospital. The clinical, diagnostic, and treatment features are reviewed.

New Insights into Parvovirus Research.

The family Parvoviridae includes an ample and most diverse collection of viruses. Exploring the biological diversity and the inherent complexity in these apparently simple viruses has been a continuous commitment for the scientific community since their first discovery more than fifty years ago. The Special Issue of 'Viruses' dedicated to the 'New Insights into Parvovirus Research' aimed at presenting a 'state of the art' in many aspects of research in the field, at collecting the newest contributions on unresolved issues, and at presenting new approaches exploiting systemic (-omic) methodologies.

Expectoration of bronchial casts in association with Ramipril treatment.

We report of a 26-year-old female patient who was referred to our centre with congestive heart failure (CHF). Acute myocarditis with a high Parvovirus B19 virus load was diagnosed by myocardial biopsy. CHF improved after start of ramipril 5 mg/d, metoprolol, diuretics, immunoglobins, and a 24-hour infusion of levosimendan. Soon after initiation of medical therapy, the patient started to expectorate bronchial casts with varying frequencies (three times per week to five times daily). Thorough pneumological workup, including histology of the casts, microbiology, and a CT scan of the lungs, did not reveal any cause for bronchial cast formation. Inhalative corticoids were started without any benefit. Two years later, cardiac catheterisation demonstrated normalised left ventricular function. LV end-diastolic pressure, however, was still elevated at 14 mmHg. Endomyocardial biopsies at this time were negative for virus genome. Finally, we changed afterload reduction therapy from ramipril to candesartan. Within 24 hours, expectoration of bronchial casts terminated. Four weeks later, re-exposition to ramipril prompted immediate re-appearance of cast formation, which again stopped with switching back to candesartan. Finally, we were to prove that treatment with ramipril resulted in bronchial cast formation in this patient.

Parvoviral infection with systemic impact and renal consequences.

Parvovirus infection is usually asymptomatic especially in immunocompetent adults. When symptomatic it can range from mild to life threatening depending on the patient's age and comorbidities. We report a case of a 40-year-old male patient with parvovirus infection who presented a purpuric rash in distal extremities, acute kidney injury, type II mixed cryoglobulinaemia and hypocomplementaemia. His renal biopsy showed a mesangioproliferative glomerulonephritis with positive immunoreactivity to C3, IgM and C1q. Parvovirus B19 was detected in the biopsy tissue by PCR. He was treated with prednisolone with total remission after 1 month. We discuss the diagnosis of kidney lesion due to parvovirus in an immunocompetent person, which is a very rare condition and its association with the cryoglobulinaemia diagnosis.

Kawasaki disease triggered by parvovirus infection: an atypical case report of two siblings.

BACKGROUND: There are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients the idea of infective agents as trigger must be considered. CASE PRESENTATION: We describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis. The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions. Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%). He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister's history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome. CONCLUSIONS: We report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction. We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.

Acute hepatitis as a prequel to very severe aplastic anemia.

Severe aplastic anemia is a rare and potentially life-threatening disease of the bone marrow often requiring allogeneic hematopoietic stem cell transplantation. Pathogenesis of the disease can vary and often remains enigmatic. Occasionally, severe aplastic anemia is associated with prior severe acute hepatitis. Differential diagnosis of acute non-viral hepatitis challenges the physician as pathogenesis remains unclear.We here present a case of a young patient presenting with acute hepatitis followed by severe aplastic anemia successfully treated with allogeneic hematopoietic stem cell transplantation. Due to immunosuppressive treatment with azathioprine for acute hepatitis of putative autoimmune pathogenesis and coincident infection with parvovirus B19, diagnosis of the sequential disease of acute hepatitis followed by severe aplastic anemia was complicated. We discuss the caveats and present a review of the literature.

Amelioration of oxidative stress using N-acetylcysteine in canine parvoviral enteritis.

Previously, antioxidants have not been evaluated for treatment of parvoviral diarrhea in dogs. In this study, antioxidant potential of N-acetylcysteine (NAC) in dogs infected with canine parvovirus with a nonblinded randomized clinical trial has been carried out. A total 18 parvo-infected dogs were randomly divided into two groups: nine parvo-infected dogs were treated with supportive treatment and nine parvo-infected dogs were treated with NAC along with supportive treatment. Simultaneously, nine healthy dogs were kept as healthy control. In parvo-infected dogs, marked hemoconcentration, leucopenia, neutropenia and oxidative stress were noticed compared to healthy dogs. The NAC treatment progressively improved the leukocyte, neutrophil, monocyte, and eosinophil counts over the time in parvovirus-infected dogs compared to dogs that received only supportive treatment. In addition, NAC treatment significantly improved glutathione S-transferase (GST) activity and decreased nitrite plus nitrate (NOx) and malondialdehyde (MDA) concentrations on day 3 and 5 compared to supportive treatment in parvo-infected dogs. However, supportive treatment alone failed to ameliorate oxidative stress in the infected dogs till day 5. The results of this study suggest that NAC represents a potential additional treatment option that could be considered to improve the health condition and minimize the duration of hospitalization in case of canine parvoviral diarrhea.

Induction Failure in Acute Leukemia or Parvovirus B19 Infection?

Parvovirus B19 infection may be seen in acute leukemia patients and clinical findings and cytopenia caused by the viral infection may complicate the evaluation of the remission status. Herein we present a standard risk pediatric acute lymphobiastic leukemia patient who developed myalgia, bone pain, bone marrow aplasia and sinusoidal obstruction syndrome at the end of the induction treatment and was diagnosed as having parvovirus B19 infection.

The Root Extract of Gentiana macrophylla Pall. Alleviates B19-NS1-Exacerbated Liver Injuries in NZB/W F1 Mice.

The nonstructural protein NS1 of human parvovirus B19 (B19) is known to exacerbate disease activity in systemic lupus erythematosus (SLE). However, no specific medicine for B19 infection is available. The roots of Gentiana macrophylla Pall. (GM), the traditional Chinese medicine "Qinjiao," have been used for centuries to treat rheumatic disease, including SLE. Herein, we aimed to investigate the effects of GM root extract (100 and 300 mg/kg body weight) on B19-NS1-exacerbated liver injury in NZB/W F1 mice; liver tissues were assessed by hematoxylin-eosin staining and immunoblotting. The GM root extract significantly decreased B19-NS1-exacerbated liver inflammation by suppressing the expressions of hepatic inducible nitric oxide synthase, cyclooxygenase type 2 (COX-2), interleukin (IL)-1ß proteins, values of serum asparate transaminase (AST) and alanine transaminase (ALT), and lymphocyte infiltration (P < .05). It also significantly reduced the B19-NS1-exacerbated hepatic matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) expressions by downregulating tumor necrosis factor (TNF)-α/NF-κB (p65) signaling. These findings suggest a therapeutic potential of GM root extract against B19-NS1-exacerbated liver inflammation in SLE.

Chronic persistent parvovirus B19 bone marrow infection resulting in transfusion-dependent pure red cell aplasia in multiple myeloma after allogeneic haematopoietic stem cell transplantation and severe graft versus host disease.

INTRODUCTION: We report a chronic persistent Parvovirus B19 (PVB19) infection despite long-term immunoglobulin substitution intravenous immunoglobulin (IVIG) and tapering of immune-suppressive therapy in a 41-year-old patient after allogeneic haematopoietic stem cell transplantation (alloHSCT) and long-term immune-suppressive therapy due to a steroid-refractory graft versus host disease (GvHD). CLINICAL COURSE: More than 18 month after alloHSCT the patient acquired a de novo transfusion-dependent pure red cell aplasia (PRCA) due to a PVB19 infection. Despite prompt tapering of GvHD-directed therapy and application of various IVIG regimens, transfusion-dependent anaemia (fourerythrocyte concentrates a month) persisted, and a high PVB19 replication is still evident for more than 3.5 years. Virological analysis at different time points showed a very high PVB19 load in the blood (range: 6.79E9-1.56E11), as well as highly elevated PVB19-IgG (range: 1.95-3.34) and -IgM (range: 1.97-9.74) levels in serology testing. Other virological parameters were not significantly elevated. After 30 months, a bone marrow (BM) examination still revealed a highly dysplastic erythropoiesis without any cellular maturation, and a high-grade expression of PVB19 within the dysplastic erythropoietic progenitor cells, consistent with a PRCA due to a PVB19 infection of the BM. We suggest that PRCA was most probably caused by a primary PVB19 infection of unknown source following alloHSCT with a PVB19-negative donor. CONCLUSION: PRCA due a PVB19 infection of the BM may persist over a long-time, despite prolonged administration of various IVIG regimen and tapering of GvHD-directed therapy. The case emphasizes the importance of PVB19 monitoring in heavily pre-treated haematological patients. Currently, PVB19-directed treatment options are extremely limited and optimized therapeutic strategies are urgently needed.

Pure red cell aplasia.

Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.

Persistent and Prolonged Parvovirus B19 Viremia in a Pediatric Patient With Acute Lymphoblastic Leukemia.

Parvovirus B19 is a small single-stranded DNA virus of the Parvoviridae family. Depending on host factors, it may produce a wide array of clinical disease states. Disease severity can range from self-limited to severe, requiring significant supportive care. Immunocompromised patients are generally affected more severely but rarely develop prolonged and persistent infections. Here, we describe a patient who was diagnosed with parvovirus during maintenance therapy for acute lymphoblastic leukemia and required therapy with intravenous immunoglobulin; the patient remained parvovirus positive according to a polymerase chain reaction testing but had no clinical symptoms for 27 months off chemotherapy.

Viral infections of the folds (intertriginous areas).

Viruses are considered intracellular obligates with a nucleic acid, either RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for the cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Though the cutaneous manifestations of viral infections are closely related to the type and the transmission route of the virus, viral skin diseases may occur in almost any part of the body. In addition to friction caused by skin-to-skin touch, skin folds are warm and moist areas of the skin that have limited air circulation. These features provide a fertile breeding ground for many kinds of microorganisms, including bacteria and fungi. In contrast to specific bacterial and fungal agents that have an affinity for the skin folds, except for viral diseases of the anogenital area, which have well-known presentations, viral skin infections that have a special affinity to the skin folds are not known. Many viral exanthems may affect the skin folds during the course of the infection, but here we focus only on the ones that usually affect the fold areas and also on the less well-known conditions or recently described associations.