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fredag 29 mars 2019

PubMed tietoa ihmiseen tarttuneista H7N9 - infektioista

https://www.ncbi.nlm.nih.gov/pubmed/30572825

2018 Dec 20;18(1):685. doi: 10.1186/s12879-018-3592-9. Muscle weakness associated with H7N9 infection: report of two cases.
Jin CN1, Tang LL2. Abstract   BACKGROUND:
The emerging avian influenza A (H7N9) virus, a subtype of influenza viruses, was first discovered in March 2013 in China. Infected patients frequently present with pneumonia and acute respiratory disorder syndrome with high rates of intensive care unit admission and death. Neurological complications, such as Guillain-Barré syndrome(GBS), and intensive care unit-acquired weakness, including critical illness polyneuropathy and myopathy, have only rarely been reported previously.  CASE PRESENTATION:
In this study, we report on two Chinese patients with H7N9 severe pneumonia presenting neurological complications. These two patients had non-immune diseases prior to the onset of virus infection. A 56-year-old female patient (case 1) and a 78-year-old female patient (case 2) were admitted because of fever, cough, chest tightness and shortness of breath. These patients were confirmed to have H7N9 infection soon after admission followed by the development of acute respiratory distress syndrome and various severe bacterial and fungal infections. The case 1 patient was found to have muscle weakness in all extremities after withdrawing the mechanical ventilator, and the case 2 patient was found when withdrawing extracorporeal membrane oxygenation, both of these conditions prolonged ventilator-weaning time. Furthermore, the case 1 patient carried the H7N9 virus for a prolonged period, reaching 28 days, and both of them stayed in the hospital for more than two months. A clinical diagnosis of intensive care unit-acquired weakness could be confirmed. However, based on results from electrophysiological testing and needle electromyography of these 2 patients, it is difficult to differentiate critical illness polyneuropathy from GBS, since no lumbar puncture or muscle and nerve biopsy were conducted during hospitalization. Following a long-term comprehensive treatment, the patients' neurological condition improved gradually. CONCLUSIONS: Although there is great improvement in saving severe patients' lives from fatal respiratory and blood infections, it is necessary to pay sufficient attention and to use more methods to differentiate GBS from intensive care unit-acquired weakness. This unusual neurological complication could result in additional complications including ventilator associated pneumonia, prolonged hospital stay and then would further increase the death rate, and huge costs.

https://www.ncbi.nlm.nih.gov/pubmed/30680746

2019 Jan 24. doi: 10.1002/jmv.25408. [Epub ahead of print]
Establishment of sandwich ELISA for detecting the H7 subtype influenza A virus.
Chen L1,2,3, Ruan F1,2,3, Sun Y2, Chen H3, Liu M3, Zhou J2, Qin K2.  Abstract
Avian H7N9 subtype influenza virus infects human with high case-fatality rate since it emerged in 2013. Although the vaccination has been rapidly used in poultry due to the emergence of highly pathogenic strain, this virus remains prevalent in this region. Thus, rapid diagnosis both in poultry and human clinic is critically important for the control and prevention of H7N9 infection. In this study, a batch of H7 subtype-specific monoclonal antibodies (mAbs) were developed and a pair of mAb, 2B6, and 5E9 were used to establish a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to quantify H7 protein and detect influenza A virus baring H7 subtype HA. The lowest detection limit for the recombinant H7 protein was 10 ng/mL and 0.5 HAU/50 μL of A/Guangdong/17SF003/2016(H7N9), 2 HAU/50 μL of A/Netherlands/219/2003(H7N7) and A/Anhui/1/2013(H7N9) for live virus, respectively. The ELISA could not only detect the prevailing H7N9 virus, but also antigenic drift H7 subtype viruses, showing excellent sensitivity and high specificity. Hence, it could serve as a valuable approach to diagnose H7 subtype virus which showed great potential to cause pandemic, as well as antigen quantification.

https://www.ncbi.nlm.nih.gov/pubmed/30592958 

2018 Dec;30(12):1200-1201. doi: 10.3760/cma.j.issn.2095-4352.2018.012.019.
[The first case of severe avian influenza A (H7N9) in Guangdong Province in 2018 successfully treated with extracorporeal membrane oxygenation].
[Article in Chinese] Li J1, Jiang H, Li B, Liang H, Wu G, Xu X, Hou L, Chen M, Ruan Z Abstract
Human infection with avian influenza A (H7N9) is easy to induce severe acute respiratory distress syndrome (ARDS), and traditional mechanical ventilation cannot correct hypoxemia, so patients may die from multiple organ failure (MOF) caused by persistent hypoxia. Extracorporeal membrane oxygenation (ECMO) can provide effective respiratory support and win time for the treatment of severe H7N9. The first case of severe H7N9 in Guangdong Province in 2018 was admitted to Zhongshan Hospital Affiliated to Sun Yat-sen University. The case was insult with severe ARDS caused by H7N9, the traditional mechanical ventilation could not correct hypoxemia, and the lung condition gradually improved with ECMO assistance. After 13 days of ECMO support, the patient was successfully weaned from ECMO and was transferred to a general ward after 55 days. After 102 days of rehabilitation, the patient was discharged from hospital and followed up for 2 months, who was in good health and had a good quality of life. This article states the diagnosis and treatment of severe H7N9 in details, providing experience for the treatment of severe H7N9 in the future.

https://www.ncbi.nlm.nih.gov/pubmed/30551738

Clinical, immunological and bacteriological characteristics of H7N9 patients nosocomially co-infected by Acinetobacter Baumannii: a case control study.
Liu WJ1,2, Zou R1, Hu Y3, Zhao M3, Quan C2, Tan S3, Luo K1, Yuan J1, Zheng H1, Liu J4, Liu M4, Bi Y1,3,5, Yan J3, Zhu B3, Wang D2, Wu G2, Liu L1, Yuen KY6, Gao GF7,8,9,10, Liu Y11.Abstract BACKGROUND: Bacterial co-infection of patients suffering from influenza pneumonia is a key element that increases morbidity and mortality. The occurrence of Acinetobacter baumannii co-infection in patients with avian influenza A (H7N9) virus infection has been described as one of the most prevalent bacterial co-infections. However, the clinical and laboratory features of this entity of H7N9 and A. baumannii co-infection have not been systematically investigated.  METHODS:
We collected clinical and laboratory data from laboratory-confirmed H7N9 cases co-infected by A. baumannii. H7N9 patients without bacterial co-infection and patients with A. baumannii-related pneumonia in the same hospital during the same period were recruited as controls. The antibiotic resistance features and the corresponding genome determinants of A. baumannii and the immune responses of the patients were tested through the respiratory and peripheral blood specimens. RESULTS: Invasive mechanical ventilation was the most significant risk factor for the nosocomial A. baumannii co-infection in H7N9 patients. The co-infection resulted in severe clinical manifestation which was associated with the dysregulation of immune responses including deranged T-cell counts, antigen-specific T-cell responses and plasma cytokines. The emergence of genome variations of extensively drug-resistant A. baumannii associated with acquired polymyxin resistance contributed to the fatal outcome of a co-infected patient. CONCLUSIONS:
The co-infection of H7N9 patients by extensively drug-resistant A. baumannii with H7N9 infection is an important issue which deserves attention. The dysfunctions of immune responses were associated with the co-infection and were correlated with the disease severity. These data provide useful reference for the diagnosis and treatment of H7N9 infection.

https://www.ncbi.nlm.nih.gov/pubmed/30126042

2018 Nov;12(11):2539-2545. doi: 10.1111/crj.12953. Epub 2018 Oct 22.
A study on mother-to-fetus/infant transmission of influenza A(H7N9) virus: Two case reports and a review of literature.
Wang J1, Xu H2, Mu C1, Chen C1, Guo L3, Chen L4, Huang JA1, Guo Q2.Abstract OBJECTIVES:
The prevention strategies for mother-to-fetus/infant transmission of H7N9 virus have not been well understood, and the study on this subject will provide further insights.  METHODS:
Reverse transcriptase polymerase chain reaction assay was undertaken to detect H7N9 virus in samples from a pregnant women, a postpartum woman, and their fetus/infant. Pathological features of tissues from the dead fetus were evaluated with hematoxylin and eosin staining. Hemagglutination inhibition assay was used to detect virus-specific antibodies. Furthermore, relevant literatures were reviewed and analyzed. RESULTS:
A 28-year-old pregnant woman was hospitalized for H7N9 infection and prescribed with oseltamivir and peramivir for 2 days before admission. The fetal heart beating stopped on day 4, the dead fetus was delivered on day 13, and the woman expired on day 26. All fetal tissues were H7N9 virus-negative. A 28-year-old woman delivered a newborn on December 20, 2016. Five days later, she developed influenza-like symptoms and was confirmed with H7N9 infection. She had close contact with her infant for 9 days. Oseltamivir and peramivir were prescribed within 2 days after illness onset. A throat swab and a pair of serum samples from the infant were all negative for H7N9 virus during 4-week follow-up. In total, ten studies referring to transplacental transmission and four reports on maternal infection of H7N9 virus were reviewed and analyzed. CONCLUSION:
No evidence showed H7N9 virus infection in both fetus and infant. The early administration of neuraminidase inhibitor seemed beneficial in preventing mother-to-fetus/infant transmission of H7N9 virus.

https://www.ncbi.nlm.nih.gov/pubmed/30069787

2018 Aug 1;20(10):38. doi: 10.1007/s11908-018-0643-8.
Zoonotic Influenza and Human Health-Part 2: Clinical Features, Diagnosis, Treatment, and Prevention Strategies.
Mehta K1, Goneau LW2,3, Wong J1,4,5, L'Huillier AG1, Gubbay JB6,7,8.Abstract PURPOSE OF REVIEW:
Zoonotic influenza viruses are those influenza viruses that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this second part of a two-part review, we discuss the clinical features, diagnostic modalities, and treatment of zoonotic influenza, and provide an overview of prevention strategies. RECENT FINDINGS:
Illnesses caused by novel reassortant avian influenza viruses continue to be detected and described; most recently
  • a human case of avian influenza A(H7N4) has been described from China. 
  • We continue to witness increasing rates of A(H7N9) infections, with the latest (fifth) wave, from late 2016 to 2017, being the largest to date. 
  • The case fatality rate for A(H7N9)
  •  and A(H5N1) infections among humans is much higher than
  •  that of seasonal influenza infections. 
  • Since the emergence of the A(H1N1) 2009 pandemic
  • and subsequently A(H7N9), testing and surveillance for novel influenzas have become more effective.
 Various newer treatment options, including peramivir, favipiravir (T-705), and DAS181, and human or murine monoclonal antibodies have been evaluated in vitro and in animal models. Armed with robust diagnostic modalities, antiviral medications, vaccines, and advanced surveillance systems, we are today better prepared to face a new influenza pandemic and to limit the burden of zoonotic influenza than ever before. Sustained efforts and robust research are necessary to efficiently deal with the highly mutagenic zoonotic influenza viruses.


https://www.ncbi.nlm.nih.gov/pubmed/29996349

2018 Jul 12;41(7):534-538. doi: 10.3760/cma.j.issn.1001-0939.2018.07.006.
[Analysis of 15 cases of avian influenza virus (H7N9) infection].
[Article in Chinese; Abstract available in Chinese from the publisher]
Objective: To describe the clinical, chest imaging, pathological manifestations and therapeutic experience of human infection with A/H7N9 virus. Methods: The features of 15 laboratory-confirmed cases of human infection with A/H7N9 virus in Taizhou, Jiangsu Province were retrospectively analyzed. Results: The 15 patients with confirmed viral pneumonia included 12 males and 3 females, with a median age of 61 years(ranging from 33 to 81 years). Twelve patients had a history of exposure to the poultry trading places, or direct contact with ill/dead avian, while 3 patients denied exposure or contact. The most common initial symptoms were fever, coughing, and respiratory distress. The illness progressed rapidly to acute respiratory distress syndrome (ARDS). Lab tests showed normal (8 cases) or decreased (7 cases)white blood cell count , decreased (13 cases) lymphocyte count and proportion , increased creatine kinase (CK, 12 cases) and lactate dehydrogenase (LDH, 15 cases), and respiratory failure (13 cases). Chest radiographic examination showed that the most common features were inflammatory infiltration in the lung, with partial consolidation. The average time of the diagnosis with influenza viral nucleic acid and onset of an oral anti-influenza drug were 7.1 days and 6.5 days. All patients were treated by antiviral drugs (oral oseltamivir 150 mg q12 h and/or intravenous paramivir 600 mg qd), with mechanical ventilation in 9 cases, glucocorticoid therapy in 5 cases (intravenous methylprednisolone in 3 and dexamethasone in 2 patients), extracorporeal membrane oxygenation (ECMO) therapy in 2 cases, continuous renal replacement therapy (CRRT) in 6 cases, and artificial liver therapy in 1 case. The pulmonary pathology was observed from post-mortem biopsy for 2 fatal cases. Patient 1 had diffuse alveolar damage with inflammatory exudation, hyaline membrane formation, and cellular infiltration. Patient 2 had widened alveolar septum, lymphocyte and monocyte cell infiltration in the alveolar septa, and interstitial fibrous proliferation. Nine patients were discharged, and 6 died. Conclusions: Patients with influenza A/H7N9 virus mostly presented with fever, cough, and were prone to progression to viral pneumonia. Once acute respiratory distress and important organ dysfunction occurred, the fatality rate was higher. Early diagnosis and rational treatment were critical for better outcomes.

https://www.ncbi.nlm.nih.gov/pubmed/29617693

2018;46(2):633-643. doi: 10.1159/000488631. Epub 2018 Mar 28.The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice.
Wu XX1, Deng XL2, Yu DS1, Yao W3, Ou HL1, Weng TH1, Hu CY1, Hu FY2, Wu NP1, Yao H1, Zhang FC2, Li LJ1. Abstract
BACKGROUND/AIMS: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. METHODS: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. RESULTS:The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. CONCLUSIONS: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.
Highly pathogenic H7N9; MF59 adjuvant; Protective immune responses; Split H7N9 vaccine

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