Critical findings of severe influenza A (H1N1) pneumonia in children

Background: Pandemic influenza A (H1N1) causes severe pneumonia in children. The mechanism of development of respiratory failure in pneumonia patients remains unknown. This report describes clinical features of childhood influenza A pneumonia. Methods: The clinical and laboratory findings of 31 H1N1 pneumonia patients hospitalized in Iwata City Hospital from 1 October 2009 to 31 January 2010 were reviewed. Intubation and mechanical ventilation were required due to respiratory failure in eight patients, who were classified as the intubation group. Other patients without mechanical ventilation were classified as the non‐intubation group. Clinical features and laboratory findings were compared between the two groups. Results: The median age was 6.3 years (range, 3–10 years). The male to female ratio was 22:9. Clinical manifestations of tachycardia, tachypnea and cyanosis were significant findings in the intubation group at admission. Lymphocytopenia was observed in both groups. Leukocytosis with neutrophilia was the risk factor for intubation. Conclusions: Tachycardia, tachypnea, cyanosis and leukocytosis with neutrophilia, could be useful predictors at admission to identify high‐risk influenza A (H1N1) pneumonia in children.     

淋巴瘤患儿感染甲型H1N1流感病毒后所致重症肺炎四例诊治分析

目的 探讨化疗期间免疫抑制的恶性淋巴瘤患儿感染甲型H1N1病毒后所致重症肺炎的临床特点及治疗.方法 回顾性分析4例非霍奇金淋巴瘤患儿化疗期间合并甲型H1N1流感肺炎的临床表现、影像学特点、误诊原因、治疗体会及预后.结果 同期收治的54例恶性血液病患儿中,甲型H1N1流感病毒感染共4例,均为恶性淋巴瘤化疗后患儿,中性粒细胞绝对值均小于0.5×109/L.起病时体温均大于39℃,伴畏寒,血压下降,迅速出现呼吸困难和低氧血症,2例继发急性呼吸窘迫综合征.C反应蛋白均大于50 mg/L,2例大于200 mg/L;4例影像学均提示广泛间实质病变.例1早期被误诊为败血症,4例患儿17次血培养均阴性,20次痰培养中2例患儿各1次痰培养真菌阳性,考虑过真菌性肺炎.4例患儿均使用了磷酸奥司他韦,第1例于第5天加用,余3例于发热的第1天加用;4例均应用了丙种球蛋白,3例应用了甲泼尼龙治疗.治疗后2例死亡,2例好转.结论 恶性淋巴瘤患儿化疗期间合并甲型H1N1流感易致重症肺炎,进展迅速,早期症状与败血症不易鉴别,影像学与单纯真菌感染不易鉴别,易误诊,死亡率高.在H1N1流感流行季节,出现高热及时做病毒筛查,及早应用磷酸奥司他韦,并予大剂量丙种球蛋白冲击及甲泼尼龙等治疗可减少病死率.     

Renal complications of seasonal and pandemic influenza A virus infections

Renal complications of influenza A virus infections are uncommon but can contribute to a deterioration in the patient’s condition, which include acute kidney injury (AKI) in critically ill patients, rhabdomyolysis, hemolytic uremic syndrome (HUS), acute glomerulonephritis (AGN), disseminated intravascular coagulation (DIC), Goodpasture’s syndrome, and acute tubulointerstitial nephritis (TIN). The clinical characteristics of AKI in critically ill patients with pandemic influenza A(H1N1) 2009 virus (A(H1N1)pdm09) infection are similar to uninfected patients. Underlying conditions associated with AKI include older age, diabetes mellitus, obesity, pregnancy, history of asthma, and chronic kidney disease. Histologic examination of the kidneys from patients with A(H1N1)pdm09 infection who died include acute tubular necrosis (ATN), myoglobin pigment, and DIC. A(H1N1)pdm09 is present in the kidneys of some patients. The clinical characteristics of patients with rhabdomyolysis associated with influenza A include younger age and the frequent occurrence of muscle symptoms. AKI occurs in approximately one third of patients with rhabdomyolysis due to influenza A. HUS is associated with A(H1N1)pdm09 as follows: Streptococcus pneumoniae-associated HUS following A(H1N1)pdm09 infection, HUS triggered by A(H1N1)pdm09 in patients with genetic complement dysregulation, and HUS associated with A(H1N1)pdm09 without known underlying disorder. AGN, Goodpasture’s syndrome, and acute TIN are extremely rare complications of influenza A virus infection. Although the pathogenesis underlying renal injuries due to influenza A virus has not been delineated, some hypotheses have been advanced, including ATN due to renal hypoperfusion or rhabdomyolysis, glomerular microthrombosis due to DIC, direct viral injury to the kidney, and an altered immune system with systemic mononuclear cell activation following influenza A virus infections.     

Experience of pandemic influenza with H1N1 in children with leukemia

It is not exactly known the risks from infection with pandemic influenza (H1N1) 2009 in children with leukemia. Here the authors present their experience in 5 children with leukemia. Pandemic influenza (H1N1) 2009 was detected in 5 patients (F/M: 3/2) at their institution. The ages of these patients were between 2 and 16 years. Four had acute lymphoblastic leukemia (ALL) and 1 acute myeloblastic leukemia (AML). Three of the ALL patients had the diagnosis of pandemic influenza (H1N1) 2009 at the same time as they were diagnosed with ALL. The remaining 2 patients were receiving intensive chemotherapy. All patients had fever, rhinorrhea, and cough. Although bronchopneumonia was seen in 3 patients, only 1 revealed respiratory distress. Stomach ache and diarrhea was seen in the patient who had no pneumonia. All treated as inpatients, but none of them required hospitalization in intensive care unit. One to 3 days after the symptoms of influenza appeared, oseltamivir (Tamiflu) was given to all patients in combination with broad-spectrum antibiotics. Fever declined to normal ranges in 1 to 3 days after treatment was started. The patients received oseltamivir for 5 to 7 days. Cell culture tests were found to be positive for influenza A and polymerase chain reaction (PCR) revealed H1N1 for all 5 patients. Although this is a very small case series, pandemic influenza (H1N1) 2009 did not seem to be very dangerous for children with leukemia if the oseltamivir treatment was given early when symptoms of influenza appeared.     

Comparison of clinical presentation of respiratory tract infections in H1N1/09-positive and H1N1/09-negative patients

The true burden of influenza in children is difficult to assess and is probably underestimated as clinical signs are usually nonspecific, and formal viral identification is rarely searched. In this study, we compare the clinical features of infections related to the new H1N1/09 influenza virus with infections due to other respiratory viruses in children consulting in a tertiary care pediatric hospital in Geneva. Between October 1, 2009 and February 10, 2010, 109 patients were recruited, with a median of age of 7 years (range 0.1–18). There were 75 H1N1/09-positive patients (69%), and 32 (43%) had identified risk factors such as asthma or a history of wheezing. Fever (87%), cough (92%), and rhinitis (85%) were the most frequent reported presenting symptoms in both patient groups. H1N1/09-positive patients were significantly older (median of 8.2 vs. 4.6 years) and were more likely to have risk factors (43% vs. 24%) and myalgias (41% vs. 20%). H1N1/09-negative patients had more wheezing episodes (29% vs. 9%), higher rates of dyspnea (28% vs. 20%) and of hospital admissions (35% vs. 16%). Conclusion: Clinical signs cannot reliably differentiate H1N1/09-positive and H1N1/09-negative patients, although we found a higher proportion of myalgias in H1N1/09-positive patients. Severity of disease was lower in H1N1/09-positive than in H1N1/09-negative patients, mostly because of a higher proportion of asthma/wheezing episodes among H1N1/09-negative patients.     

Serum KL‐6 and surfactant protein D in children with 2009 pandemic H1N1 influenza infection

Background: A global pandemic influenza A (H1N1) outbreak occurred in 2009. Rapid progress of respiratory distress is one of the characteristic features of pandemic influenza A (H1N1) infection. The physiologic mechanism causing hypoxia in pandemic influenza A (H1N1) infection, however, has not been elucidated. Methods: The serum levels of KL‐6 and surfactant protein D (SP‐D) were evaluated in 21 cases of pandemic influenza A (H1N1) infection associated with chest radiographic abnormality in order to estimate alveolar involvement. The clinical features were also analyzed. Results: All of the patients had high fever, and rapidly progressed to respiratory distress within several days of disease onset. Despite mild radiographic abnormality in these patients, dyspnea was severe and they had low blood oxygen saturation levels. Many of the patients had a history of allergic diseases including asthma. Serum KL‐6 and SP‐D levels on admission were 191 ± 69 U/mL and 32.6 ± 18.9 ng/mL, respectively. These two levels were still below the upper normal limit 1 week later. There were no clear relationships between specific clinical symptoms and KL‐6 or SP‐D levels. All patients were treated with oseltamivir and/or zanamivir, and improved without mechanical ventilation management. Conclusion: KL‐6 and SP‐D elevation were not significant in pandemic influenza A (H1N1) infection associated with chest radiographic abnormality. In pandemic influenza A (H1N1) infection, alveolar involvement was estimated to be little, and severe respiratory distress was probably caused by obstruction of peripheral bronchi.     

儿童重症和危重症2009甲型H1N1流感临床特征

目的 报道儿童2009甲型H1N1流感重症与危重症的临床特征.方法 对150例经咽拭子实时荧光定量PCR检测确诊为2009甲型H1N1流感重症与危重症患儿的临床资料进行分析.结果 150例患儿中,男103例,女47例,年龄中位数为5岁;≥5岁81例,合并基础疾病21例.常见的表现依次为发热142例(95%),咳嗽133例(89%),呕吐35例(23%),喘息29例(19%),腹痛24例(16%),嗜睡11例(7%),惊厥9例(6%),肌痛9例(6%)和腹泻9例(6%).常见的检验异常为外周血白细胞计数异常60例(40%),C反应蛋白增高49例(33%),乳酸脱氢酶增高4.4例(29%),肌酸激酶增高38例(25%)和天冬氨酸转氨酶增高29例(19%).并发症主要为肺炎97例(65%),脑病18例(12%)和心肌炎7例(5%).使用奥司他韦治疗109例(73%),使用糖皮质激素治疗35例(23%).32例(21%)入住ICU,13例接受气管插管机械通气,14例接受支气管镜检查及冲洗.145例(97%)患儿治愈出院,5例死亡,其中3例死于脑病,1例死于急性呼吸窘迫综合征,1例死于继发性真菌性脑膜炎.结论 重症和危重症2009甲型H1N1流感主要发生在没有基础疾病的年长儿,其表现及检验异常比较广泛.神经系统并发症发生率较高,严重的脑病可引起死亡.早期行支气管镜检查及冲洗有可能减少肺部并发症引起的死亡.     

儿童甲型H1N1流感危重患者临床特点分析

目的 探讨甲型H1N1流感重症和危重病例的高危因素、临床特点、治疗和预后.方法 描述性研究12例入住PICU的危重甲型H1N1流感确诊病例.结果 12例中男10例,女2例;年龄2～10岁,中位数年龄6.0岁;4例(33.3%)有基础疾病;重症和危重症表现出现在发病后平均(2.3±0.9)d,发病后平均(2.7±1.2)d入PICU;表现为肺炎11例,病毒性脑炎1例.11例肺炎中合并急性肺损伤7例,急性呼吸窘迫综合征3例,哮喘持续状态1例.肺炎患儿中2例发生休克.入PICU后予奥司他韦抗病毒、免疫球蛋白、甲泼尼龙、支气管扩张剂等治疗,可疑细菌或真菌感染者予抗生素和抗真菌治疗.6例予鼻塞持续气道正压通气,4例气管插管机械通气.治愈或好转出院8例,2例死亡,2例好转仍住院治疗.结论 有呼吸系统慢性疾病或免疫抑制状态、合并细菌或其他感染是甲型H1N1流感发生重症、危重症和死亡的危险因素.危重病例主要表现为肺炎合并呼吸衰竭和休克.早期奥司他韦抗病毒治疗、呼吸支持、控制混合感染、免疫调节等综合治疗措施可有效控制病情进展,降低病死率.     

Factors associated with hypoxemia in children infected with pandemic H1N1 2009 influenza virus

Background: Hypoxemia was found to be a major cause of death from pandemic H1N1 2009 influenza (pH1N1) infection. There are limited data on factors associated with hypoxemia in children infected with pH1N1 influenza virus. Methods: Factors associated with hypoxemia were investigated using univariate and multivariate analysis in 76 hospitalized pediatric patients with laboratory‐confirmed H1N1 influenza virus infection at Gyeongsang National University Hospital in Jinju, South Korea, from August 2009 to January 2010 by retrospective chart review. Results: Hypoxemia occurred in 17 children (22%), of whom three were admitted to an intensive care unit and one died. Hypoxemic patients were significantly more likely to have a higher respiratory rate, pulse rate, white blood cell count (WBC), and C‐reactive protein level, as well as a longer hospital stay. Respiratory rate and WBC count at admission were independently associated with hypoxemia as determined on multivariate analysis, and this association was found to be clinically significant. Conclusion: Although a higher WBC count and respiratory rate may not be specific for pHINI but represent the degree of disease severity for any infectious respiratory disease in general, clinicians can use these parameters at admission as useful, early indicators of disease severity in pediatric pH1N1 infection.     

The burden of seasonal and pandemic influenza in infants and children

The burden of influenza is unevenly distributed, with more severe outcomes in children aged <5 years than older children and adults. In spite of this, immunisation policies for young children are far from universal. This article provides an overview of the published evidence on the burden of influenza in children worldwide, with a particular interest in the impact of pandemic influenza in 2009–2010 (caused by the H1N1pdm09 virus). In an average season, up to 9.8 % of 0- to 14-year olds present with influenza, but incidence rates can be markedly higher in younger children. Children aged <5 years have greater rates of hospitalisation and complications than their older counterparts, particularly if the children have co-existing illnesses; historically, this age group have had higher mortality rates from the disease than other children, although during the 2009–2010 pandemic the median age of those who died of influenza was higher than in previous seasons. Admissions to hospital and emergency departments appear to have been more frequent in children with H1N1pdm09 infections than during previous seasonal epidemics, with pneumonia continuing to be a common complication in this setting. Outcomes in children hospitalised with severe disease also seem to have been worse for those infected with H1N1pdm09 viruses compared with seasonal viruses. Studies in children confirm that vaccination reduces the incidence of seasonal influenza and the associated burden, underlining the importance of targeting this group in national immunisation policies. Conclusions: Children aged <5 years are especially vulnerable to influenza, particularly that caused by seasonal viruses, and vaccination in this group can be an effective strategy for reducing disease burden.     

2009 Influenza A H1N1 infections: delays in starting treatment with oseltamivir were associated with a more severe disease

Respiratory failure has been the main severe complication described in pediatric patients with influenza A H1N1 2009 (pandemic H1N1) infection. We describe the pandemic H1N1 2009 disease in children who required hospital admission and the patients' data associated with pediatric intensive care unit admission. Respiratory failure was the main complication. Extrapulmonary manifestations were also observed. Of the 127 patients, 24 required pediatric intensive care unit admission. Four patients died. Patients admitted with chronic conditions and those in whom oseltamivir was delayed more than 72 hours had a more severe disease.     

小儿甲型H1N1流感危重症诊治体会

目的 探讨小儿甲型H1N1流感危重症患儿的发病特点及治疗措施.方法 2009年10月5日至11月15日期间我院PICU收治11例出现甲型H1N1流感样症状合并重症肺炎、急性呼吸窘迫综合征(ARDS)患儿,对其发病特点、治疗方法及转归等资料进行分析.结果 11例甲型H1N1流感样患儿合并重症肺炎、ARDS,其中6例经咽拭子检测甲型H1N1流感病毒核酸阳性.患儿平均年龄3.9岁(10个月～11岁).所有患儿都表现为发热和呼吸系统症状,从发病到出现危重症状的时间为5～10 d.6例行机械通气治疗.目前全部病例存活,无一例死亡.6例机械通气患儿已有4例安全脱机,2例仍在机械通气中.结论 重症甲型H1N1流感患儿病初为流感症状,无特殊临床表现;病情可在短时间内迅速加重,重症患儿以呼吸困难、低氧血症为突出表现;婴幼儿可伴有嗜睡、烦躁等神经系统症状;重症患儿肺部病变广泛,进展迅速,可在短时间内出现纵隔及皮下气肿、ARDS甚或肺出血并随之出现多脏器功能障碍综合征.     

Clinical features of hospitalised children with 2009 H1N1 influenza virus infection

Clinical features and outcome of 2009 H1N1 influenza virus in the paediatric setting is ill-defined. The epidemiologic and clinical features of children with confirmed H1N1 influenza virus infection admitted to an Italian tertiary paediatric hospital from August through December 2009 were evaluated. A total of 63 children (mean age 4.3 years) were studied; of these, 29 (46%) had chronic underlying diseases. The most frequent symptoms and signs at admission were fever (97%), cough (60%) and respiratory disturbances (24%). Forty patients (63.5%) had H1N1-related complications: 32 (51%) pulmonary diseases, three (5%) neurological disorders, such as acute encephalitis or acute disseminated encephalomyelitis, and two (3%) haematological alterations. Three patients were admitted to the Intensive Care Unit. Most children (81%) were treated with oseltamivir: one developed rash during treatment; no other adverse events were noticed. All children survived without sequelae. In conclusions, 2009 H1N1 influenza virus infection in children is associated with a wide spectrum of clinical manifestations. Neurological disorders are not exceptional complications. Oseltamivir therapy seems safe also in infants.     

Clinical relevance of immunoglobulin subclasses in children with chronic pulmonary diseases

In 52 children (age 4-19.5 years; 17 female, 35 male) with chronic chest symptoms IgG-Subclass levels were measured by radial immunodiffusion techniques. Thirteen children had proven bronchiectasis, 22 chronic bronchitis and 17 steroid dependent asthma bronchiale. Cystic fibrosis, alpha-1-antitrypsin deficiency, tuberculosis and chronic foreign bodies were excluded in each patient; all of them showed normal levels of total IgG. Four children (3 with bronchiectasis, one with steroid dependent asthma bronchiale) had a complete lack if IgG4. In two children with chronic bronchitis one showed fluctuating levels of IgG2 and IgG4 and another deficiency of IgG3. All patients with an isolated IgG4 deficiency were treated with immunoglobulins. Of 3 patients with bronchiectasis one improved, two remained unchanged as shown by positive sputum cultures and of chronic chest symptoms. One patient with steroid dependent asthma bronchiale markedly improved during immunoglobulin therapy. It is concluded, that early screening of IgG subclass deficiency is indicated in all children with chronic chest symptoms.     

Myocarditis in a pediatric case of pandemic 2009H1N1 influenza

We report a 6‐year‐old boy with no major disease history or allergic conditions initially presented with pneumonia, progressed to acute respiratory distress syndrome and acute myocarditis caused by pandemic 2009H1N1 influenza diagnosed with RT‐PCR testing, successfully managed with mechanical ventilation and percutaneous cardiopulmonary support system. Marked transient elevation of IgE in acute phase of the disease and the subsequent diagnosis of atopic asthma in our patient suggested a possible role of an underlying allergic condition in the clinicopathological process. Critically ill 2009H1N1‐infected patient with acute respiratory failure should carefully be physiologically monitored together with serial assessment of biomarkers aiming at a favorable cardiac outcome by giving the timely diagnosis and intervention.     

Analysis of Fatal Cases of Pandemic Influenza A (H1N1) Virus Infections in Pediatric Patients with Leukemia

Background: Pandemic influenza A/H1N1/2009 virus usually causes mild illness in healthy children. Chronic medical conditions are recognized as increasing the risk for complications of influenza virus infection. Although most studies including children with acute leukemia and H1N1 virus have reported no deaths, some anectodal reports with low patient numbers have reported mortality rates as high as 28.5%. Here, we report patients with leukemia and H1N1 virus and review the literature. Methods: Medical records of all children with leukemia and H1N1 virus in our institution were reviewed for demographic, clinical, and laboratory data. We also carried out a systematic review of the English-language literature. Among the 24 articles found, only patients with leukemia and pandemic H1N1 infections were reviewed by two independent reviewers. Results: Eight of 98 children who received chemotherapy for leukemia were diagnosed with pandemic H1N1 infection. One developed pneumonia and acute respiratory distress syndrome (ARDS) and died. Another one developed hemophagocytic lymphohistiocytosis (HLH) and died due to secondary infection during the 6th week of treatment for HLH. In our study, 2 of 8 patients had a fatal course (25%), compared with an overall mortality of 2.5% in the studies retrieved from PubMed (6/232). Conclusion: Pandemic H1N1 influenza virus caused mortality in patients with ARDS or HLH; an unexpected finding for pandemic H1N1 (2009) influenza virus. Thus, for children with leukemia and infected with H1N1 virus, short- and long-term complications should be kept in mind during evaluation.     

Predictors of Mortality in Hospitalized Children with Pandemic H1N1 Influenza 2009 in Pune, India

Objective

To analyse the factors associated with increased mortality among Indian Children with H1N1.

Methods

Data were abstracted from available hospital records of children less than 12?y of age, who were admitted to Sassoon General Hospital in Pune, India, with confirmed pandemic 2009 H1N1 influenza infection from August 2009 through January 2010. Logistic regression analysis was used to identify clinical characteristics associated with mortality.

Results

Of 775 pediatric cases admitted with Influenza Like Illness (ILI), 92 (11.8%) had confirmed H1N1 influenza infection. The median age of HIN1 cases was 2.5?y; 13 (14%) had an associated co-morbid condition. Median duration of symptoms was 4?d (interquartile range (IQR), 3?C7?d). All 92 H1N1 cases received oseltamivir and empiric antimicrobials on admission. Intensive care unit (ICU) admission was required for 88 (96%) children, and 20 (23%) required mechanical ventilation.Fifteen children (16%) died; mortality was associated with presence of diffuse alveolar infiltrate on admission chest radiography (odds ratio (OR) 45, 95%CI :5.4?C370; p?p?=?0.001), SpO₂ <80% on admission (OR 32.8, 95% CI: 5.8?C185.5; p?p?n?=?4 each, 27%) with gram positive organisms consistent with severe viral and bacterial co-infection.

Conclusions

Hypoxia, ARDS and use of corticosteroids in children with ARDS who were mechanically ventilated were the factors associated with increased odds of mortality. Necropsy also suggested bacterial co-infection as a risk factor.