Experience of Therapy for Pneumonia In Hematopoietic Stem Cell Transplant Recipients Infected by Influenza 2009 H1N1.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4553-4553
Author(s):  
Yi Luo ◽  
Huarui Fu ◽  
Yamin Tan ◽  
Yanlong Zheng ◽  
Jimin Shi ◽  
...  

Abstract Abstract 4553 In March 2009, a novel influenza H1N1 2009 virus was firstly detected in Mexico and then spread throughout the world rapidly. Till now, data about severe cases infected by 2009 H1N1 following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are sparse, with only 11 anecdotal cases reported. We first describe three cases of influenza A/H1N1 2009 infection following allo-HSCT in China, including the first report in a haploidentical allo-HSCT recipient. The main clinical presentation in all cases are classic pneumonia-like symptoms and H1N1 virus was isolated from throat swabs in all patients. All patients received oral oseltamivir 75 mg twice a day, broad-spectrum antibiotic and anti-fungi drugs were given at the same time for co-infection. Two patients achieved complete resolution with this treatment regimen, the haploidentical HSCT recipient finally died of ARDS. Our cases suggest combination of oseltamivir, more effective of prophylaxis of co-infections and better supportive care is an effective treatment for influenza A/H1N1 2009 pneumonia in immunodeficient patients. The first case, a 16-year-old male, was diagnosed with acute lymphocytic leukemia (ALL-L2) in April 2008. He received HLA-identical sibling peripheral blood stem cells transplantation (allo-PBSCT) in October 23, 2008. Acute and chronic GVHD were not observed. He was admitted to our hospital for pharyngodynia, rhinobyon, exacerbated cough accompanied by pricked dyspnea on November 2009. Broad-spectrum antibiotic were administered for 3 days and no significant clinical improvement was observed. High-solution chest CT showed bilateral multiple flaky infiltrating. Influenza 2009 H1N1 virus was subtyped in his throat swab by real-time quantitative PCR (RT-PCR) analysis using validated CDC published primer/probe sets septic for variant 2009 H1N1 virus. The second case, a 25-year-old female, was diagnosed with acute lymphocytic leukemia (ALL-L2, B-cell, Ph-) in August 2008. She received HLA-identical unrelated donor (10/10 alleles matching) allo-PBSCT in April, 2009. She developed dermatosclerosis-like extensive cGVHD (skin) but the symptom was not improved after being treated with prednisone, thalidomide and tacrolimus. She was admitted to our hospital for palm infection in December, 2009. Chest CT showed lung infection and round lesion near the pleura. She was diagnosed with H1N1 influenza by RT-PCR analysis in throat swabs. The third case, a 42-year-old male, was diagnosed with acute lymphocytic leukemia (ALL-L2) with positive Bcr/Abl P190 fusion gene in October 2008. He received HLA-haploidentical sibling (his daughter) allo-PBSCT in April 2009. The patient developed grade II aGVHD (skin) on day 14 after transplantation, He achieved excellent response by being treated with prednisone and FK506. He was admitted to our hospital for skin rush and hyperglycemia in December, 2009. His oxygen saturation was 93.3% on room air. Chese CT showed interstitial ground glass-like changes in both lungs, and consolidation in both lobus inferior pulmonis. The patient developed progressive tachypnea after 4 days and was diagnosed with H1N1 influenza by RT-PCR analysis in throat swabs. All patients were nursed in H1N1-ICU ward for further treatment as soon as being diagnosed. Oseltamivir (75 mg twice a day) was given with broad-spectrum antibiotic and anti-fungi drugs. The first and second patients’ symptoms were improved after 2 weeks, and recurrent throat swab examination was negative. The third patient was continued mechanical ventilation, Chest CT show infection was progressive and infiltrating in the whole lung. In January 7, 2010, the patient's oxygen saturation decreased to 50% and malignant ventricular arrhythmias were observed. Although with cardio pulmonary resuscitation for more than 1 hour, the patient died of ARDS. Our experience highlights on the severity of 2009 H1N1 infection in post-transplantation recipients. Haploidentical transplantation is an independent adverse prognostic factor. Oseltamivir is an effective therapy for pneumonia infected by 2009 H1N1, broad-spectrum antibiotic and anti-fungi drugs should be given at the same time. Disclosures: No relevant conflicts of interest to declare.

2009 ◽  
Vol 45 (3) ◽  
pp. 203-204 ◽  
Author(s):  
David M. Whiley ◽  
Seweryn Bialasiewicz ◽  
Cheryl Bletchly ◽  
Cassandra E. Faux ◽  
Bruce Harrower ◽  
...  

2012 ◽  
Vol 33 (1) ◽  
pp. 58-62 ◽  
Author(s):  
Yoko Nukui ◽  
Shuji Hatakeyama ◽  
Takatoshi Kitazawa ◽  
Tamami Mahira ◽  
Yoshizumi Shintani ◽  
...  

Objective.To evaluate the seroprevalence and risk factors for 2009 influenza A (H1N1) virus infection among healthcare personnel.Design.Observational cross-sectional study.Patients and Setting.Healthcare workers (HCWs) in an acute care hospital.Methods.Between September 14 and October 4, 2009, before 2009 H1N1 vaccination, we collected serological samples from 461 healthy HCWs. Hemagglutination-inhibition antibody assays were conducted. To evaluate the risk factors of seropositivity for 2009 H1N1 virus, gender, age, profession, work department, usage of personal protective equipment, and seasonal influenza vaccination status data were gathered via questionnaires.Results.Our survey showed that doctors and nurses were at highest risk of seropositivity for the 2009 H1N1 virus (odds ratio [OR], 5.25 [95% confidence interval {CI}, 1.21–22.7]). An increased risk of seropositivity was observed among pediatric, emergency room, and internal medicine staff (adjusted OR, 1.98 [95% CI, 1.07–3.65]). Risk was also higher among HCWs who had high titers of antibodies against the seasonal H1N1 virus (adjusted OR, 1.59 [95% CI, 1.02–2.48]).Conclusions.Seropositivity for the 2009 H1N1 virus was associated with occupational risk factors among HCWs.Infect Control Hosp Epidemiol 2012;33(1):58-62


2011 ◽  
Vol 18 (3) ◽  
pp. 520-522 ◽  
Author(s):  
Jesse Papenburg ◽  
Mariana Baz ◽  
Marie-Ève Hamelin ◽  
Chantal Rhéaume ◽  
Julie Carbonneau ◽  
...  

ABSTRACTSerology improves influenza diagnosis by capturing cases missed by reverse transcriptase PCR (RT-PCR). We prospectively evaluated microneutralization and hemagglutination inhibition assays for 2009 influenza A (H1N1) virus diagnosis among 24 RT-PCR-confirmed cases and 98 household contacts. Compared to hemagglutination inhibition, microneutralization demonstrated a higher level of concordance with RT-PCR (kappa = 0.69 versus kappa = 0.60) and greater sensitivity (83% versus 71%;P= 0.016).


Author(s):  
J Sembiring ◽  
O Sianipar

H1N1 virus is an influenza virus family orthomyxoviridae, which clinical symptoms consist of: fever, cough, sore throat and headache. The virus can spread from person to person through airborne droplets and so a good infection control in the community or in healthworkers is needed, for instance by washing hands properly and PPE (Personal Protective Equipment). In October 4, 2009 there were over375.000 reported cases in which 4500 people were died. On June 11, 2009 the WHO stairs announced that H1N1 is the first pandemicin the 21st century. (The Indonesia people province was infecting by H1N1with 20 deaths until August 5, 2009). The purpose of thisarticle is to find out the epidemiological aspects as well as the diagnosis of influenza A H1N1 virus. From the website was found about1.110.000 sources, and after downloading them are selected as they are written only in the bibliography. From the searched informationobtained, it was known that H1N1 infection diagnosis begins with the discovery of heat (temperature ≥ 100° F [37.8° C]) and cough or sore throat. No cause other than influenza that is called with ILI was found. The informed laboratory examination is divided into three parts are confirmed if ILI was found as well as the virus in the throat or nasal swab by RT-PCR and/or virus culture; probably the ILIhas positive results of influenza A RT-PCR, but if the results are negative including the laboratorial findings, the basis of epidemiologyin this case was only suspected. Laboratory plays an important role in the establishing of the H1N1 infection diagnosis Rapid diagnosisis important to reduce infection, to protect patients from complications by antiviral treatment in the right time and also to provideimmediate information for the public.


Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 1013-1018 ◽  
Author(s):  
Richard Gorlick ◽  
Erdem Goker ◽  
Tanya Trippett ◽  
Peter Steinherz ◽  
Yaroslav Elisseyeff ◽  
...  

Abstract Methotrexate (MTX) transport was examined in 27 patients with untreated acute lymphocytic leukemia (ALL) and 31 patients with relapsed ALL using a previously described fluorescent MTX analog (PT430) displacement assay (Blood 80:1158, 1992). Only 13% of untreated patients were considered to have impaired MTX transport, whereas more than 70% of relapsed patients had evidence of impaired MTX transport. To further characterize the basis for this defect, Northern analyses for the reduced folate carrier (RFC) were performed on the RNA available from the leukemic blasts of 24 patients in whom MTX transport had been measured. Six of nine samples with impaired MTX transport had decreased RFC expression (one had no detectable RFC expression), while three had no decrease in RFC expression. None of 15 samples with normal MTX transport had decreased RFC expression. A reverse-transcriptase polymerase chain reaction (RT-PCR) assay was developed to quantitate RFC mRNA expression more accurately. Decreased RFC expression was demonstrated in six of the nine samples with impaired MTX transport, confirming the results obtained by Northern blot. These data indicate decreased RFC expression associated with impaired MTX transport is observed in relapsed ALL following treatment with MTX-containing therapy.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1622-1622 ◽  
Author(s):  
Medhat Shehata ◽  
Dita Demirtas ◽  
Stefanie Tauber ◽  
Susanne Schnabl ◽  
Martin Bilban ◽  
...  

Abstract Fludarabine and cyclophosphamide are the backbone of therapy for patients with CLL. The addition of rituximab leads to further improvement of response rates and progression free survival (results from the randomized CLL8 study of the GCLLSG). However, a considerable number of patients have insufficient or short responses to FC or RFC and there is a need to identify factors influencing response or resistance to therapy. The aims of this study are to identify gene expression associated with response or resistance before the start of therapy, to investigate changes in the expression of specific genes or pathways associated with response or resistance during the first cycle of FC and RFC, to provide a rationale for the additional use of novel drugs to improve remission and overcome resistance. We investigated peripheral blood samples from 20 patients receiving FC (n=10) or RFC (n=10) by gene expression profiling, flow cytometry, RT-PCR and western blotting before and during therapy. Sixteen patients received FC or RFC as first line (8 within the CLL8 study) and 4 as second line treatment. All patients were in stage Binet B or C. Gene expression was analyzed and correlated to good (CR or PR) or poor clinical response (SD or PD) at the end of therapy based on NCI-WG/IWCLL criteria. CD19+ cells were harvested by cell sorting before therapy, 24 hours after FC (FC arm), 24 hours after rituximab, and 24 hours after FC (RFC arm). Microarray analysis was performed using Affymetrix U133A gene chips. Genes with a consistent pattern of expression (high or low) in the majority of samples in the good or poor response group were further analyzed. Overall, 9 patients responded adequately to therapy (3 CR, 7 PR), while 11 did not (7 SD, 3PD). Unmutated IgVH status and poor risk cytogenetics were more frequent in poor responders. Gene expression signature before treatment showed that overexpression of 39 genes strongly correlated with response, while overexpression of 20 genes (including HSPA1B, IFI6, APP, CEACAM1, CD9, GAB1, INPP5F) was associated with resistance. Changes in expression after initiation of treatment was also analyzed. Seven genes (including CENTD1, HBA2, COL9A2 and APRIN) were significantly upregulated after rituximab in non-responders. Upregulation of 13 genes (including PMAIP1, SFRS11, CLK1, EFHC1, MRPL39, TUG1, TBRG1, CD49d, PTPRC) after R-FC and 7 genes (including ITPKB, LOC641298, CD44, TAF5) after FC was associated with poor response (resistance) to RFC and FC respectively. Many of these genes are involved in regulation of apoptosis, cell cycle, integrin and PI3-K signaling Therapeutic antibodies or inhibitors against some of these targets are already available. RT-PCR analysis demonstrated a significant downregulation of Akt1 mRNA 24 hours after rituximab infusion in RFC group but no significant changes were observed in patients receiving FC alone. In vitro exposure to rituximab confirmed its in vivo effect and resulted in a significant downregulation of Akt1 and PI3-K-p85 mRNA expression. FACS analysis demonstrated a decrease in the percentage and mean fluorescence intensity (MFI) of surface CD20 after rituximab infusion. This effect was associated with a significant change in total amount and phosphorylation state of CD20 in the RFC group. There was also a decrease in the MFI of CD44 and CD23 after rituximab in the majority of patients in the RFC group but this effect was not consistent in the FC group. In conclusion, we have identified a set of markers associated with good or poor response to FC or RFC before therapy and during the first cycle of treatment. The data provide a rationale for targeted drug combinations to overcome resistance and improve response to therapy in CLL.


2020 ◽  
Vol 215 (5) ◽  
pp. 1065-1071 ◽  
Author(s):  
Zhilan Yin ◽  
Zhen Kang ◽  
Danhui Yang ◽  
Shuizi Ding ◽  
Hong Luo ◽  
...  

2013 ◽  
Vol 193 (2) ◽  
pp. 487-491 ◽  
Author(s):  
Mario Bermúdez de León ◽  
Katia Peñuelas-Urquides ◽  
Miguel E. Aguado-Barrera ◽  
María José Currás-Tuala ◽  
Brenda L. Escobedo-Guajardo ◽  
...  

2010 ◽  
Vol 84 (9) ◽  
pp. 4194-4203 ◽  
Author(s):  
Jessica A. Belser ◽  
Debra A. Wadford ◽  
Claudia Pappas ◽  
Kortney M. Gustin ◽  
Taronna R. Maines ◽  
...  

ABSTRACT The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a representative human triple-reassortant swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, cytokine production, and lung histology. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and the 1918 virus. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases. Histologically, infection with the 2009 viruses resulted in lesions in the lung varying from mild to moderate bronchiolitis with occasional necrosis of bronchiolar epithelium and mild to moderate peribronchiolar alveolitis. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses.


2010 ◽  
Vol 163 (2) ◽  
pp. 470-473 ◽  
Author(s):  
Tao Jiang ◽  
XiaoPing Kang ◽  
Yongqiang Deng ◽  
Hui Zhao ◽  
Xiaofeng Li ◽  
...  

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