Novel H1N1 influenza A virus infection in a patient with acute rejection after liver transplantation

BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppression.There are limited reports of 2009 H1N1 influenza in liver transplant recipients,especially in China. METHODS:We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 influenza A virus.He received therapy for acute rejection after transplantation and was confirmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir(75 mg, orally twice daily)and had a benign hospital course,with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS:The 2009 H1N1 influenza in this hospitalized transplant recipient was relatively mild,and prolonged viral shedding was not noted.Oseltamivir can be a valid measure in immunocompromised individuals.

In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2 D ligand（N-[（1S,6R）-5-amino-5-{[（2R,3S,4S）-3,4-dihydroxy-4-（hydroxymethyl） tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-（1-ethylpropoxy）-1-cyclohexene-1-carboxylate） had better binding energy values than standard oseltamivir.AD3BF2 D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2 D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

Reduning plus ribavirin display synergistic activity against severe pneumonia induced by H1N1 influenza A virus in mice

OBJECTIVE:To investigate synergistic effect of Reduning(RDN)injection plus ribavirin against severe pneumonia induced by H1 N1 influenza A virus in mice.METHODS:We established a mouse model of severe pneumonia induced by influenza A virus by infecting Balb/c mice with CA07 virus.We randomly assigned the infected mice into four groups,and treated them with normal saline(NS group),RDN(injection,86.6 mg/kg),ribavirin(injection,66.6 mg/kg)or double Ribavirin plus RDN group,the same dosage as used in the single treatments)for 5 d.Lung index and lung pathology were recorded or calculated in terms of the curative effective.Cytokines,NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome related protein including caspase-associated recruitment domain(CARD)domain Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1 and NOD-like receptor family,pyrin domain containing 3(NLRP3),and reactive oxygen species were simultaneously investigated.RESULTS:RDN plus ribavirin treatment,not RDN or ribavirin alone,provided a significant survival benefit to the influenza A virus-infected mice.The combination treatment protected the mice against severe influenza infection by attenuating the severe lung injury.The combined treatment also reduced the viral titers in mouse lungs and lung index,downregulated their immunocytokine levels,including IL-1βand IL-18,and down regulated the NLRP3,especially the transcription and translation of caspase-1.Meanwhile NS group had significantly higher reactive oxygen species(ROS)expression which could was dramatically reduced by the treatment of RDN plus ribavirin.CONCLUSION:Our study showed that RDN combined with ribavirin could protect the mice,and reduce the lung immunopathologic damage caused by severe influenza pneumonia.The mechanism could be that it reduced ROS produce and inhibited NLRP3 inflammasome activation so that mainly lower the downstream inflammatory cytokines IL-1βand IL-18.

Influenza A pandemic （H1N1） 2009 virus infection

The clinical spectrum of the 2009 pandemic influenza A （H1N1） infection ranged from self-limited mild illness to progressive pneumonia, or even a fatal outcome. We summarize the clinical manifestations, risk factors for severe and fatal cases, pathologic findings and treatment of this disease in this paper based on current reports from different regions of the world.

Hospitalized patients with novel influenza A （H1N1） virus infection： Shanghai, June-July 2009

Background From late May 2009, sporadic imported cases of novel influenza A （HIN1） were continuously confirmed in Shanghai, but there were few reports on its clinical presentation in China. The aim of the study was to investigate the demographic and clinical features of the laboratory-confirmed cases and the treatment with oseltamivir. Method We performed a retrospective study in the Shanghai Public Health Clinical Center （SHAPHC）, reviewing the medical records of the laboratory-confirmed patients derived from June 10 to July 20, 2009. Results A total of 156 cases were enrolled, of whom 152 had a history of recent travel. The mean age was 22.6 years and 89 cases （57.1%） were males. The most common symptoms were fever, cough, and sore throat, with children more likely to run a temperature above 38.5℃ than adults. The mean leucocyte count was 5.4×10^9/L, the mean neutrophil count 3.2×10^9/L and the mean lymphocyte count 1.4×10^9/L. Other findings included a normal range or elevated level of C-reactive protein （CRP） and glutamic-pyruvic transaminase and a normal or decreased level of prealbumin; the levels of prealbumin and CRP were significantly lower in the children than in the adults. Fifty-two patients had abnormal chest CT results, with small unilateral or bilateral pulmonary infiltrates, axillary and mediastinal lymphadenopathy and local pleural thickening, while no cases showed symptoms of hypoxia. All the patients received oseltamivir and recovered without complications, but the duration of fever and virus shedding were significantly longer in the children than in the adults. Conclusions Travel-related circulation may be an important reason for the H1N1 epidemic in the non-epidemic areas, and the virus caused mild respiratory symptoms. The infection in children was more severe in terms of prealbumin levels, temperature, the duration of fever and virus shedding. Oseltamivir was effective for H1N1, but more effective in the adults than in the children.

Clinical features of initial cases of 2009 pandemic influenza A （H1N1） in Macao, China

Background The first case of pandemic influenza A （H1N1） virus infection in Macao Special Administrative Region （SAR） of the People＇s Republic of China was documented on June 18, 2009. Subsequently, persons with suspected infection or of contact with suspected cases received screening. All the confirmed cases were hospitalized and treated with oseltamivir. Their clinical features were observed. This may help for better management for later patients and be of benefit to the government of Macao SAR to adjust its strategy to combat the pandemic influenza A （H1N1） virus infection more efficiently. Methods From June to July 2009, the initial 72 cases of influenza A （H1N1） in Macao were hospitalized in Common Hospital Centre S. Januario （CHCSJ）. The infection was confirmed by real-time reverse-transcriptase polymerase chain reaction （RT-PCR）. The clinical features of the disease were closely observed and documented. Oseltamivir was given to all patients within 48 hours after the onset of disease and maintained for 5 days. Results The mean age of the 72 patients was 21 years old. Forty of them were men and 32 were women. The median incubation of the virus was 2 days （1 to 7 days）. The most common symptoms were fever （97.2%） and cough （77.8%）. The rate of gastrointestinal symptoms including nausea, vomiting, and diarrhea was 2.8%. Fever typically lasted for 3 days （1 to 9 days）. The median time from the onset to positive results of real-time RT-PCR was 6 days （3 to 13 days）. After treatment with oseltamivir, most patients became afebrile within 48 hours. Only one aged patient with a history of glaucoma and hypothyroidism was found to have lung infiltration on chest X-ray. Conclusions The initial cases of pandemic influenza A （H1N1） virus infection in Macao SAR showed that most of the infected persons had a mild course. The virus could be detected by real-time RT-PCR within a median of 6 days from the onset. Oseltamivir was effective.

Sixty-two severe and critical patients with 2009 influenza A （H1N1） in Shanghai, China

Background Pandemic influenza A （H1N1） emerged rapidly in China in May 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A （HIN1） disproportionately affects younger ages and causes generally mild disease. To characterize disease progress, comorbidities, and treatment outcomes among consecutive severe and critically ill patients in a hospital served as a reference center for the care of patients with HIN1 in Shanghai, China.Methods A retrospective study on 62 severe and critically ill patients with 2009 influenza A （H1N1） was conducted in Shanghai Public Health Clinical Center. Demographic data, symptoms, comorbidities, disease progression, treatments, and clinical outcomes were collected for analysis.

Clinical outcomes of influenza-like illness treated with Chinese herb- al medicine： an observational study

OBJECTIVE: To present and analyze treatmentsand clinical outcomes of Chinese patients with influenza-like illness.METHODS: We conducted a multi-site observational study from December 2009 to April 2010. Patients with influenza-like illness from 45 hospitals were enrolled. Patients received Chinese herbal medicine(CHM), conventional treatments, or CHM plus conventional treatments(combination treatment) according to the guidelines for influenza A/H1 N1 2009 in China. The primary outcomes were the time to alleviation of symptoms and the incidence of complications. The secondary outcomes were the time until becoming afebrile, incidence of severe illness, testing negative on an influenza A viral test, and total medical fees.RESULTS: In total, 5967 patients were enrolled. The percentages of patients prescribed CHM alone, conventional treatment, and combination treatment were 27.8%, 5.1%, and 67.7%, respectively. There were no significant differences in the time to alleviation of symptoms, incidence of complications,time to becoming afebrile, or rate of severe illness among the CHM, conventional, and combination treatment groups. The rates of testing negative on the influenza virus A rapid test and H1 N1 virus test were 90.3% and 76.3%, respectively. However,significant differences were found in the total medical fees among the three groups: CHM treatments were more economical than the other two treatments.CONCLUSION: The efficacy of CHM for influenza-like illness was not different from that of conventional treatments, but it was more economical.