Correlation of IL-1, IL-6, IL-10 Concentrations to Ovarian Hyperstimulation Syndrome and Effect of Intravenous Immunoglobulin on Ovarian Hyperstimulated Rats

Objective To investigate the correlation of interleukin（IL）-1,IL-6 and IL-10 concentrations to ovarian hyperstimulation syndrome（OHSS） and whether intravenous immunoglobulin（IVIG） has the effects on ovarian hyperstimulated rats. Methods Immature female Wistar rats were divided into control group, OHSS group （n=13） and IVIG group（n=13）. For the latter two groups, pregnancy mare serum gonadotropin（PMSG）and human chorionic gonadotropin（hCG） were given to induce OHSS, and rats in IVIG group were treated with immunoglobulin. Forty-eight hours after administration of hCG, capillary permeability was evaluated from the Evans blue dye（EB） concentration in the ovaries and the EB concentration in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. Rats＇ blood samples and ovaries were obtained to be measured for IL-1, IL-6 and IL-10 by ELISA. Results In OHSS group, total weights of bilateral ovaries and the ovarian EB concentration were significantly higher than those in others（P〈0.05）. Both serum and ovarian concentrations of IL-1 were significantly higher in OHSS and IVIG groups than those in control group （P〈0.05）. The ovarian concentrations of IL-6 and IL-10 in IVIG group were significantly lower than those in control group（P〈0.05）. Furthermore, the ovarian IL-10 concentration in IVIG group was significantly lower than that in OHSS group（P〈0. 05）. Conclusion Inflammation involved IL-1 in OHSS rats plays an important role. Vascular permeability was mostly increased in ovaries of hyperstimulated rats. It appears that ovaries of OHSS rats may be the primary places of inflammation. IVIG treatment resulted in statistically significant reductions in ovaries＇ weights and ovarian vascular permeability of OHSS rats, with a decreased level of ovarian IL-10. It implys that IVIG have a beneficial effect in reducing the severity of OHSS in the experimental model maybe by restrainning IL-10.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

BACKGROUND： The established procedure for ABO-incompatible liver transplantation（ABO-I LT） was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin（IVIG） for ABO-I LT in patients with acute liver failure（ALF）.METHODS： The data from 101 patients who had undergone liver transplantation（LT） for ALF were retrospectively analyzed.The patients were divided into two groups： ABO-compatible liver transplantation group（ABO-C LT, n=66） and ABO-I LT group（n=35）. All the patients in the ABO-I LT group received a single dose of rituximab（375 mg/m2） and IVIG（0.4 g/kg per day） at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol.Quadruple immunosuppressive therapy including basiliximab,corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.RESULTS： The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%,respectively（P〉0.05）, and the graft survival rates were 80.0%and 86.3%, respectively（P〉0.05）. Two patients（5.7%） suffered from antibody-mediated rejection in the ABO-I LT group.Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.CONCLUSIONS： The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Role of intravenous immunoglobulin in suspected or proven neonatal sepsis

Neonatal sepsis remains the major cause of mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay in newborn infants. Despite of advances in technology and optimal antibiotic treatment,incidence of neonatal sepsis and its complications remains unacceptably high especially in developing countries. Premature neonates in particular are at higher risk due to developmentally immature host defence mechanisms. Though not approved by Food and Drug Administration(FDA) U. S. A,off label use of intravenous immunoglobulin as prophylactic or adjuvant agent in suspected or proven neonatal infections continues in many countries. In a recent large multicenter clinical trial by International Neonatal Immunotherapy Study(INIS) group, the use of polyvalent IgG immune globulin was not associated with significant differences in the risk of major complications or other adverse outcomes in neonates with suspected or proven sepsis. Hence,use of intravenous immunoglobulin in suspected or proven neonatal sepsis is not recommended. The expense of prophylactic use of intravenous immunoglobulin administration for both term and preterm newborn population,given the minimal benefit as demonstrated by many individual studies and by meta-analysis is not justified.

Intravenous Immunoglobulin Treatment of Recurrent Miscarriage:an Update of Placebo-controlled Trials

Background Immunological disturbances which may be treated with intravenous immunoglobulin (IvIg) play a significant role in the majority of patients with recurrent miscarriage (RM). The present study aimed to review the current knowledge about IvIg treatment in RM primarily based on results from published placebo controlled trials. Seven placebo controlled trials were identified comprising a total of 343 patients. The background variables, the treatment protocols and the results were extremely different between the trials. Among the patients with secondary RM, a meta analysis showed that the pooled odds ratio for live birth among IvIg treated women compared with women infused with placebo was 1.69 (95 % CI = 0.72～3.96, not significant). IvIg also seemed to be efficacious in patients with repeated second trimester intrauterine fetal deaths. A new big placebo controlled trial should be conducted which focus on RM patients with secondary RM or recurrent second trimester fetal deaths. Sufficient IvIg doses should be given with optimal time intervals.

Haemolytic Anaemia Following High Dose Intravenous Immunoglobulin Treatment for Epidermolysis Bullosa Acquisita

Background: Epidermolysis bullosa aquisita (EBA) is a severe acquired blistering skin disease that is often resistant to prednisolone but can respond well to intravenous immunoglobulin infusion (IVIg). Main Observations: We describe the case of a 35 years old male patient with EBA who developed clinically significant haemolytic anaemia with a drop in Hb from 15.3 g/dL to a nadir of 8.4 g/dL within 5 days post IVIg infusion. The patient was blood group A and the IVIg batch was found to have a high titre of anti-A immunoglobulin. Conclusions: IVIg is an effective treatment for EBA. Haemolysis associated with IVIg has not previously been reported in the dermatology literature but review of data from other specialties shows that the problem is well recognised. Dermatologists using IVIg should be aware of this potential complication and patients should be consented appropriately and warned about this potential side effect.

A Systematic Review Incorporating Meta-Analysis on the Effectiveness of Intravenous Immunoglobulin Versus Corticosteroids in the Treatment of Pediatric Myocarditis

Background:Concerns have been raised about the efficacy of intravenous immunoglobulin and corticosteroids in pediatric myocarditis;however,the relationship between the risk and efficacy of these two therapies in children with myocarditis varies.Methods:A systematic review on seventeen studies was conducted in July 2020,which included 1,960 subjects at the baseline,with 788 receiving intravenous immunoglobulin and 142 receiving corticosteroids.The mean difference(MD)or odds ratio(OR)with 95%confidence intervals(Cis)was calculated to assess the prognostic role of both treatments using dichotomous and continuous methods with random or fixed-effect models.Results:The use of intravenous immunoglobulin was significantly associated with a lower mortality rate or heart transplantation in children with myocarditis(OR,0.55;95%CI,0.40-0.77,^<0.001)compared with the control group.However,corticosteroids were not significantly associated with the same parameters(OR,0.72;95% CI,0.31-1.63,p=0.43).The use of intravenous immunoglobulin was not significantly related to improving left ventricular ejection in children with myocarditis(OR,2.30;95% CI,-9.65-14.25,p=0.71)and so were corticosteroids(MD,5.17;95% CI,-0.26-10.60,p=0.06).Conclusion:The use of intravenous immunoglobulin might have an independent risk relationship with a lower mortality rate or heart transplantation and is recommended in children with myocarditis to prevent complications.

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in children

Background We aimed to explore predictive measures for intravenous immunoglobulin(IVIG)resistance in children with Kawasaki disease(KD).Methods Patients diagnosed with KD were enrolled in this study.Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups.Independent predictors of IVIG resistance were analyzed,and a predictive model for KD children with IVIG resistance was constructed.Results A total of 277 children with KD,180 boys and 97 girls,aged 2-128(median 23)months,were enrolled in the study.Compared with the IVIG-responsive group,the IVIG-resistant group had higher levels of the peripheral neutrophil count,mean platelet volume,mean platelet volume-to-lymphocyte ratio and C-reactive protein,and total serum bilirubin,but lower levels of peripheral lymphocyte count,serum albumin and serum prealbumin.Age(in months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis.A logistic regression model and a scoring system were set up,where cut-off values of—0.46 and 6.5 points yielded sensitivities of 83.9%and 77.4%,and specificities of 74.8%and 61.0%,respectively.The areas under the curve(AUC)were 0.808 in the logistic regression model,and 0.750 in the scoring system.Conclusion Our model for predicting IVIG-resistant children with KD,involving age(months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment,is helpful for clinical prediction of children with IVIG-resistant KD.

PLACENTAL INTRAVENOUS IMMUNOGLOBULIN (PtIVIG) FOR TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE (CGVHD)

Plasma immunoglobulin has been used widely in clinic for the prophylaxis and treatment of infections in patients after bone marrow transplantation(BMT).However,there are no hard data demonstrating that it can act against GVHD,

Transient positive antimitochondrial M2 in sera of patients with connective tissue diseases after intravenous immunoglobulin infusions

Background:Although antinuclear antibodies(ANAs),anti‐SSA and anti‐Ro52,are present in immunoglobulin preparations,it is unknown whether intravenous immunoglobulin(IVIG)therapy influences the testing of serum autoantibodies in patients with connective tissue diseases(CTDs).The present study aimed to investigate the dynamic change over time of serum ANA‐related autoantibodies in patients with CTDs receiving IVIG therapy.Methods:Serum ANA‐related autoantibodies were monitored in two patients with CTD before IVIG therapy and at different times after therapy.These autoantibodies were tested in different batches of immunoglobulin preparations from seven pharmaceutical companies.Results:One patient developed a new ANA pattern(cytoplasmic dense fine speckled pattern,AC‐19)just after IVIG therapy.Both patients developed de novo positivity for AMA‐M2 and anti‐SSA,but returned negative 1 month after IVIG therapy.The residual liquid in patients'immunoglobulin preparations showed positive ANAs with a high titer of AC‐19(1:640),a low titer of the nuclear fine speckled pattern(AC‐4,1:80),positive AMA‐M2,and positive anti‐SSA.ANA‐related autoantibodies were tested in 16 batches of immunoglobulin preparations and all had positive ANAs with two patterns:AC‐19(1:640 or 1:320)and AC‐4(1:80).AMA‐M2 and anti‐SSA were positive in 100%of the batches.Conclusion:Our study highlights high‐titer AMA‐M2 autoantibodies in immunoglobulin preparations and suggests their transient transfer into a patient's circulation via IVIG therapy.To avoid incorrect clinical decisions based on postinfusion antibody titers,our data recommend retesting 1–2 months after high‐dose IVIG immunomodulatory treatment.

A case of pyoderma gangrenosum responding to high-dose intravenous immunoglobulin therapy

Pyoderma gangrenosum （PG） is a rare ulcerative cutaneous condition with distinctivecharacteristics, and the aetiology is not clear yet. PG is commonly associated with inflammatory bowel disease including ulcerative colitis and Crohn＇s disease. This condition is within the spectrum of the neutrophilic dermatoses. The features of PG are not specific histopathologically. Commonly, it is characterized by the presence of marked neutrophilic infiltrates in the dermis. The treatment of PG usually requires systemic corticosteroids or other immunospressive medications, and its course is chronic and relapsing. Some cases are resistant to these treatments. On the other hand, long-term usage of those medications naturally causes serious side effects, and an alternative effective and safe therapy is required to avoid the clinical problems associated with the drugs.

Demyelinating neuropathy in patients with hepatitis B virus: A case report

BACKGROUND Hepatitis B rarely leads to demyelinating neuropathy,despite peripheral neuropathy being the first symptom of hepatitis B infection.CASE SUMMARY A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves.Serological testing showed that these symptoms were due to hepatitis B.After undergoing treatment involving intravenous immunoglobulin and an antiviral agent,there was a notable improvement in his symptoms.CONCLUSION Although hepatitis B virus(HBV)infection is known to affect hepatocytes,it is crucial to recognize the range of additional manifestations linked to this infection.The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented;hence,prompt diagnostic and treatment are essential.The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Human parvovirus B19-associated early postoperative acquired pure red cell aplasia in simultaneous pancreas-kidney transplantation:A case report

BACKGROUND Acquired pure red cell aplasia(aPRCA)related to human parvovirus B19(HPV B19)is rarely reported in simultaneous pancreas-kidney transplantation(SPKT)recipients;there has yet to be a case report of early postoperative infection.In this current study,we report the case of a Chinese patient who experienced the disease in the early postoperative period.CASE SUMMARY A 63-year-old man,with type 2 diabetes and end-stage renal disease,received a brain dead donor-derived SPKT.Immunosuppression treatment consisted of tacrolimus,prednisone,enteric-coated mycophenolate sodium(EC-MPS),and thymoglobulin combined with methylprednisolone as induction.The hemoglobin(Hb)level declined due to melena at postoperative day(POD)3,erythropoietinresistant anemia persisted,and reticulocytopenia was diagnosed at POD 20.The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43.Metagenomic next-generation sequencing(mNGS)of a blood sample identified HPV B19 infection at POD 66.EC-MPS was withdrawn;three cycles of intravenous immunoglobulin(IVIG)infusion therapy were administered;and tacrolimus was switched to cyclosporine.The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period.The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements.CONCLUSION HPV B19-associated aPRCA can occur at an early period after SPKT.An effective therapy regimen includes IVIG infusion and adjustment of the immunosuppressive regimen.Moreover,mNGS can be used for the diagnosis and to reflect disease progression.

An effective initial polytherapy for children with West syndrome

Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies:A case report

BACKGROUND Paraneoplastic neurological syndrome(PNS)is a rare complication in patients with cancer.PNS can affect the central,peripheral,autonomic nervous system,neuromuscular junction,or muscles and cause various neurological symptoms.Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibodypositive neurological paraneoplasms are common,but coexistence of both types has not been described in the literature.CASE SUMMARY Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers.A 55-year-old woman was admitted to our hospital with unsteadiness while walking.The patient had a history of breast cancer two years previously.Chest computed tomography revealed a 4.6 cm×3.6 cm mass in the right lung,which was diagnosed as small-cell lung cancer(SCLC).Blood test was positive for anti-Yo antibodies,and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies,and the neurological symptoms were considered to be related to the paraneoplasm.The patient was treated with a course of intravenous immunoglobulin,without noticeable improvement.After being discharged from hospital,the patient underwent regular chemotherapy for SCLC and periodic reviews.The patient’s neurological symptoms continued to deteriorate at the follow-up visit in April 2021.CONCLUSION This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies.The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Granulomatosis with polyangiitis presenting as high fever with diffuse alveolar hemorrhage and otitis media: A case report

BACKGROUND Granulomatosis with polyangiitis is a necrotizing inflammation of small andmedium-sized vessels accompanied by formation of granuloma, involvement ofprimary granulomatous upper and lower respiratory tracts, glomerulonephritis,and vasculitis of small vessels.CASE SUMMARY Herein, we described a case of a 52-year-old man admitted with pulmonarynodules and high fever. Autoantibody workup revealed that the patient waspositive for c-anti-neutrophil cytoplasmic antibodies and proteinase-3 antineutrophilcytoplasmic antibodies. Pulmonary biopsies revealed a localgranulomatous structure. The patient received therapy with methylprednisoloneand intravenous immunoglobulin, and his clinical symptoms improved.CONCLUSION Intravenous immunoglobulin may act on granulomatosis with polyangiitis similarto immunosuppressants.

Kawasaki disease without changes in inflammatory biomarkers:A case report

BACKGROUND Kawasaki disease(KD)is diagnosed based on clinical features.Blood tests and other tests are auxiliary diagnostic tools.Since KD is a disease caused by arterial inflammation,many patients with KD have elevated levels of inflammatory biomarkers,such as C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and serum amyloid A protein(SAA)in blood tests.We report our experience of a patient with KD who did not have elevated levels of inflammatory biomarkers.CASE SUMMARY A 1-year-old boy presented with a 3-day history of fever.Five of the six symptoms of KD were observed,except for changes in the lips and oral cavity.Blood tests revealed no elevation in CRP,ESR,or SAA levels.Although the blood test results were atypical,the patient was diagnosed with KD based on clinical symptoms and was admitted to the hospital for treatment.The patient was administered intravenous immunoglobulin(IVIG)and aspirin.Despite commencing treatment,the fever persisted;therefore,additional IVIG was administered,the dosage of aspirin was increased,and ulinastatin was added.Three doses of IVIG were administered and the fever resolved on day 11 of KD symptoms started.Blood tests performed during hospitalization showed normal levels of inflammatory biomarkers.We examined leucine-rich alpha-2-glycoprotein 1-a protein that is elevated during the acute phase of KD.The protein levels did not increase during hospitalization.CONCLUSION This case suggests the need to identify criteria and biomarkers for detecting KD conditions that do not require KD treatment.

Hypereosinophilic syndrome presenting as eosinophilic gastroenteritis disorder and splinter hemorrhages:A case report

BACKGROUND Eosinophilia and related organ damage are extensively studied hot topics among rare disorders.Any addition to the cohort of available case reports of the same will be adding knowledge for better management of this less known entity.CASE SUMMARY In this article,we describe a 27-year-old Indo-Aryan man who presented with abdominal pain,abdominal distension,and loose stools for variable days.He had splinter hemorrhages in the majority of fingernails.He was diagnosed with predominant eosinophilic gastrointestinal involvement with bowel obstruction and ascites,and was managed with intravenous immunoglobulin.He was subsequently treated with oral low dose steroid therapy and responded completely.CONCLUSION Our experience is evidence that prompt management of this hypereosinophilic lethal gastrointestinal(all three layers)infiltrative disease provides a cure and avoids complications.Splinter nail hemorrhages may be seen in the same disease.

Tricky Presentation of Multisystem Inflammatory Syndrome in Children (MIS-C) with in Pediatric

Introduction: In emergence a COVID patient with multisystem inflammatory syndrome in children (MIS-C), associated with SARS-CoV-2, has shown increasing number among pediatric. Even the same presentation of Kawasaki disease we have to keep in mind MIS-C, in order to reach a consensus on this new disease in the future. Three variations of the disease patterns were reported: a group of children with increase in inflammatory activity and persistent fever, without criteria for Kawasaki disease, a second group with Kawasaki disease criteria, and a third group with shock, coronary aneurysms, severe cardiac dysfunction, and gastrointestinal symptoms. Classic Kawasaki disease is self-limited vasculitis which affects medium-sized vessels, almost occurred in children under five years old. Here, we bring a Saudi case, present to emergency department in Prince Sultan Military Medical City. Case report: 10 years old female, medically free, presented with abdominal pain, fever and skin rashes. Patient had history of COVID-19 infection 1 month before presentation. Initial investigations showed acute kidney injury with elevated inflammatory markers. Conclusion: Further evidence of the increase in the incidence of pediatric MIS-C, temporarily is associated with SARS-CoV-2. Physician should give more attentions to this new diagnosis with more fatal outcomes than Kawasaki cases.

Treatment of multisystem inflammatory syndrome in children

Background Multisystem inflammatory syndrome in children(MIS-C),a relatively uncommon but severe pediatric complication,is associated with coronavirus disease 2019(COVID-19).A variety of treatment approaches,including intravenous immunoglobulins(IVIGs),glucocorticoids(GCs)and biologic agents,such as anakinra and infliximab,have been described for the management of COVID-19-related MIS-C.Anticoagulant therapy is also important.However,a well-developed treatment system has not been established,and many issues remain controversial.Several recently published articles related to the treatment of MIS-C have been released.Hence,in this review,we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically.Data sources We reviewed the literature on the treatment of MIS-C through 20 September 2023.The PubMed/Medline,Web of Science,EMBASE,and Cochrane Library databases were searched with the combination of the terms"multisystem inflammatory syndrome","MIS-C","PIMS-TS","therapy","treatment","drug","IVIG","GCs","intravenous immunoglobulin","corticosteroids","biological agent",and"aspirin".Results The severity of MIS-C varies,and different treatment schemes should be used according to the specific condition.Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C.Conclusions MIS-Cis a disease involving multiple systems and has great heterogeneity.With the accumulation of additional experience,we have garnered fresh insights into its treatment strategies.However,there remains a critical need for greater standardization in treatment protocols,alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols.

Pure Red Cell Aplasia Caused by Parvovirus B19 in Patients with Human Immunodeficiency Virus Infection: A Series of Four Cases

Parvovirus B19(B19V)infection can cause pure red cell aplasia(PRCA)in patients with human immunodeficiency virus(HIV)infection.Intravenous immunoglobulin(IVIG)is a preferred treatment option.From July 2019 to March 2022,four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA.Blood investigations revealed severe anemia and the B19V genome.Therefore,the four patients were diagnosed with B19V-induced PRCA.All four patients received red blood cell transfusion in the setting of antiretroviral therapy,and two of the four patients received intravenous immunoglobulin(IVIG).After 3-7 months of treatment,all four patients recovered,although two did not receive IVIG.This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.