Measles Outbreak in Pediatric Hematology and Oncology Patients in Shanghai, 2015 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Despite substantial progress toward measles control are making in China, measles outbreaks in immunocompromised population still pose a challenge to interrupt endemic transmission. This study aimed to investigate the features of measles in pediatric hematology and oncology patients and explore the reasons behind the outbreak.</p><p><b>METHODS</b>We collected demographic, epidemiological, and clinical data of immunocompromised measles children. All suspected measles cases were laboratory-confirmed based on the presence of measles IgM and/or identification of measles RNA. The clinical data were statistically analyzed by t-test for continuous variables and Fisher's exact test for categorical variables.</p><p><b>RESULTS</b>From March 9 to July 25 in 2015, a total of 23 children with malignancies and post hematopoietic stem cell transplantation (post-HSCT) were notified to develop measles in Shanghai. Of these 23 patients with the median age of 5.5 years (range: 11 months-14 years), 20 (87.0%) had received 1-3 doses of measles vaccine previously; all patients had fever with the median fever duration of 8 days; 21 (91.3%) had cough; 18 (78.3%) had rash; 13 (56.5%) had Koplik's spot; 13 (56.5%) had complications including pneumonia and acute liver failure; and five (21.7%) vaccinated patients died from severe pneumonia or acute liver failure. Except the first patient, all patients had hospital visits within 7-21 days before measles onset and 20 patients were likely to be exposed to each other.</p><p><b>CONCLUSIONS</b>The outcome of measles outbreak in previously vaccinated oncology and post-HSCT pediatric patients during chemotherapy and immunosuppressant medication was severe. Complete loss of protective immunity induced by measles vaccine during chemotherapy was the potential reason. Improved infection control practice was critical for the prevention of measles in malignancy patients and transplant recipients.</p>

Thrombin generation increasing with age and decreasing with use of heparin indicated by calibrated automated thrombogram conducted in Chinese / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Calibrated Automated Thrombogram(CAT) is a test to monitor the generation of thrombin. It can be described by four parameters: lag time, peak thrombin, endogenous thrombin potential (ETP) and time to peak (ttPeak). This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/low molecular weight heparin.</p><p><b>METHODS</b>Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool (NPP, n=25) spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean±2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model.</p><p><b>RESULTS</b>The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648±2.465 min, 367.39±151.93 nmol/L, 2277±1030 nmol/L•min and 6.372±4.280 min respectively. Age was linearly correlated with lag time (r=-0.6583, P<0.0001), peak thrombin (r=0.4863, P<0.0001), ETP (r=0.3608, P<0.0014) and ttPeak (r=-0.6313, P<0.0001). The values of ETP/peak ratio were linearly correlated with concentrations of heparin.</p><p><b>CONCLUSION</b>The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.</p>

Clinical characteristics and molecular epidemiology of the novel influenza A (H1N1) infection in children in Shanghai / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the epidemiological features, genetic drift in the epitopes of hemagglutinin (HA) of the novel influenza A (H1N1) virus and oseltamivir-resistant variants characterized by H275Y and N295S mutations in children in Shanghai since the outbreak.</p><p><b>METHOD</b>Between June 2009 and May 2012, a prospective surveillance study was carried out in Shanghainese children who attended the outpatient clinic of Children's Hospital of Fudan University for influenza-like illness. One-step real-time fluorescence quantitative RT-PCR was performed to detect seasonal influenza A and influenza B virus and the novel influenza A (H1N1) virus in the respiratory samples. Genetic drift from the vaccine strain in HA epitopes of the novel influenza H1N1 virus and the molecular markers associated with oseltamivir resistance in neuraminidase (NA) were analyzed.</p><p><b>RESULT</b>Out of 3475 enrolled cases, the novel influenza A (H1N1) virus was confirmed virologically in 222 (6.4%) otherwise healthy children with 133 (59.9%) being boys and 89 (40.1%) girls. The median ages of children with the novel influenza A (H1N1) virus infection during the first wave from August 2009 to February 2010 and the second wave from December 2010 to February 2011 were 53.5 months and 32.0 months, respectively (Z = -4.601, P = 0.000); 119 (46.9%) had the close contact with persons suffering from fever or respiratory infection, of whom, 68 (57.1%) contacts were family members and 47 (39.5%) contacts were classmates. During the outbreak in 2009-2010 season, 66 (40.9%) were exposed to primary index cases, school students were the major exposure subjects, accounting for 50.0%. The nucleotide sequences of HA1 gene were highly homologous between the vaccine strain A/California/07/2009 and Shanghai circulating novel influenza A (H1N1) strains and only S83P mutation in epitope E of HA was detected inclusively in the circulating strains. The H275Y and N295S amino acid mutations associated with oseltamivir resistance were not found in the circulating novel influenza (H1N1) strains.</p><p><b>CONCLUSION</b>Two major waves of the novel influenza A (H1N1) outbreaks occurred in Shanghainese children during 2009-2011. Institutional children were the major affected individuals during the 2009 pandemic wave. Households and schools were the main sites of transmission among children during influenza pandemic. Influenza vaccination should be enhanced in children and their close family contacts. The novel influenza A (H1N1) virus in Shanghai has not undergone significant genetic changes. Oseltamivir is effective for the treatment of the novel influenza A (H1N1) virus.</p>

Profiles of innate immune receptors and cytokines in peripheral blood mononuclear cells in children with measles / 中华儿科杂志

<p><b>OBJECTIVE</b>The aim of this study was to explore the roles and clinical significance of innate immune receptors and cytokine in children with measles.</p><p><b>METHOD</b>The children with measles hospitalized in the department of infectious diseases, Children's Hospital of Fudan University during 2009-2011 were enrolled into measles group, while the healthy children examined in well baby clinic were enrolled into control group. The mRNA expression of TLR2/3/4/7, melanoma differentiation-associated gene-5 (MDA-5), retinoic acid-inducible gene I (RIG-I), IFN-α/β and IL-10 in peripheral blood mononuclear cells were detected by real-time PCR. The protein levels of IFN-α, IFN-β and IL-10 in plasma were measured using ELISA. SPSS 13.0 software was applied to analyze the difference between two groups.</p><p><b>RESULT</b>Data from a total of 98 patients in measles group and 59 children in control group were collected. The mRNA expressions of TLR2, MDA-5 and RIG-I had no statistical significance between two groups (P > 0.05, respectively). The relative mRNA expressions of TLR3, TLR4, TLR7 in measles group (2.25 ± 0.74, 2.05 ± 0.72, 2.12 ± 0.29) were significantly lower than those in control group (2.09 ± 0.78, 1.90 ± 0.75, 1.87 ± 0.68) (P < 0.01; respectively). Both IFN-α and IFN-β had significantly decreased mRNA expressions in measles patients (2.41 ± 1.31, 2.47 ± 1.26) compared with those in controls (2.22 ± 0.48, 2.35 ± 0.64)(P < 0.01 respectively); however, IL-10 mRNA levels significantly increased (2.49 ± 0.58 vs. 2.62 ± 0.95) (P < 0.001). The IL-10 levels in plasma in measles group were significantly higher during the whole period of fever [<5 d group: 29.89 (25.82-38.15) ng/L and ≥ 5 d group:34.55 (28.26-38.70) ng/L] than that in control group [25.15 (24.20-27.38) ng/L] (P < 0.05 respectively).</p><p><b>CONCLUSION</b>TLR3/4/7 mRNA expression was low in peripheral blood mononuclear cells of measles patients. Levels of IL-10 were significantly raised in the early stage after infection and lasted for a long time, and reduced IFN-α levels in plasma were associated with the fever durations of measles patients. These results indicated that multiple TLRs and cytokines may participate in the immune response after measles virus infection.</p>

The first confirmed pediatric case with H7N9 avian influenza virus infection in China / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the clinical and epidemiological aspects of avian influenza A (H7N9) virus infection in children.</p><p><b>METHOD</b>The clinical data of the first confirmed pediatric case of avian influenza A(H7N9) virus infection were collected, and the epidemiological information, presenting symptoms, laboratory investigation, management and outcome were analyzed. The data of the pediatric cases were also compared with those of the adults cases.</p><p><b>RESULT</b>The case reported in this paper was a previously healthy 3.6-year-old boy residing in rural area of Shanghai. He had onset of fever and mild rhinorrhea on 31 March 2013 and he was afebrile and well since April 3. Influenza A (H7N9) virus was detected in his nasopharyngeal sample collected on 1 April through national Influenza-like Illness surveillance using real-time reverse transcriptase PCR and virus culture.His family raised domestic poultry with no apparent disease and there was no virological evidence of H7N9 infection. Monitoring and testing of 16 contacts had not found any secondary infection.</p><p><b>CONCLUSION</b>The clinical course of H7N9 avian influenza virus infection in children was relatively mild as compared to adult cases. The source of infection and detail of exposure for children have not been known yet. Continued surveillance studies of mild and severe respiratory disease and subclinical infection are essential to further characterize the epidemiology and clinical spectrum of this emerging H7N9 virus infection in children.</p>

Clinical analysis of children with severe hand-foot-and-mouth disease in Shanghai / 中华儿科杂志

<p><b>OBJECTIVE</b>To retrospectively analyzed the clinical features and epidemiology of children with severe hand-foot-and-mouth disease during 2009 and 2010 in Shanghai to investigate some risk factors with fatal cases.</p><p><b>METHOD</b>All the clinical records and laboratory results of serious patients were collected. A retrospective study was performed.</p><p><b>RESULT</b>A total of 748 serious patients were enrolled into this study, and the ratio of male to female was about 1.7:1; 724 patients were categorized into stage 2 with 254 patients in 2009 and 470 in 2010; 24 patients were categorized into stage 3 with 17 in 2009 and 7 in 2010. The rate of severity in 2010 (1.5%) was lower than in 2009 (6.3%) (χ2=12.836, P<0.01). Seven patients of stage 3 died, with the fatality 29.2%, which was higher than in stage 2 (P<0.01). The children aged between 3 months 10 days to 12 years 9 months with onset median age of 25 months. Among them, 77.1% patients aged between 1 and 4 years which also accounted for 79.2% of the fatal cases (19/24). But there was no significant difference between the age and the severity (χ2=0.804, P>0.05). Fever (100%), vomiting (57.0%) and myoclonus jerk (62.3%) were the most frequent symptoms occurred in those serious cases. The average period of fever in children of stage 2 and 3 was (4.10±1.40) d and (5.05±1.05) d, respectively, which indicated significant difference between the two groups (t=3.173, P<0.05). The average values of white-blood-cell counts and blood glucose in fatal patients were (14.8±6.25)×10(9)/L and (8.63±3.51) mmol/L. They were higher when compared to those in stage 2 with the white-blood-cell counts of (11.8±4.23)×10(9)/L and blood glucose of (5.51±2.14) mmol/L (P<0.05). But there was no significant difference in C-reactive protein or cerebrospinal fluid white-blood-cell counts; A total of 182 patients were enrolled for MRI study during the acute stage with 37 (37/182, 20.3%) presented abnormal findings. Among them, most frequent findings were hyperintense lesions seen in brain stem (11 cases). A stage 3 case who died presented brain edema on MRI examination.</p><p><b>CONCLUSION</b>The epidemic of HFMD has some correlation with the area, season, health condition of the family and gender of the children. Children under 4 years of age especially those who lived in rural areas were susceptible to the HFMD. Frequent vomiting or myoclonus jerk may indicate the central nervous system involvement. But persistent high fever may indicate tendency to deteriorate. Some laboratory examinations can help find the fatal cases at an early time.</p>

Analysis of 12 children with novel influenza A (H1N1) virus infection / 中华儿科杂志

<p><b>OBJECTIVE</b>Since late March 2009, a novel influenza H1N1 strain emerged in humans in Mexico and the United States. It has rapidly spread to many countries on different continents, prompting unprecedented activation of pandemic preparedness plans. The present study aimed to investigate the characteristics of children with the novel influenza A (H1N1) virus infection.</p><p><b>METHOD</b>Twelve cases with influenza A (H1N1) infection were diagnosed according to the criteria of the Center for Disease Control and Prevention (CDC) of China during 1 May to 15 July 2009 in the Pediatric Hospital of Fudan University were analyzed. Influenza A (H1N1) RNA was detected by RT-PCR in CDC Shanghai China.</p><p><b>RESULT</b>All the 12 children with the novel influenza A (H1N1) virus infection were imported cases, aged from 11 months to 14 years 7 months, 7 of whom were boys, 5 were girls. Five cases contacted closely with influenza A (H1N1) patients; 12 cases had fever and no vomiting or diarrhea; 7 had cough or runny nose or anorexia. One had shortness of breath. Of the 11 cases who could tell about symptoms correctly, 6 had sore throat, 3 had stomachache, and none had muscle pain. Two of the 12 cases had pneumonia, and the disease in 1 of them was fatal and needed intensive care. One case was isolated and treated at home. The 11 cases hospitalized were treated according to the guidance of influenza A (H1N1) diagnosis and treatment issued by the Ministry of Health of China. Ten hospitalized cases were treated with oseltamivir. All the cases recovered completely. The median length of hospital stay was 8.1 days (range, 6 to 16), and the time of negative test results of influenza A (H1N1) RNA from illness onset to collection of samples for viral testing was from 5 to 15 days.</p><p><b>CONCLUSION</b>Symptoms among children with the novel influenza A (H1N1) virus infection were classic and the majority of the cases we treated had a mild clinical course if they were isolated and treated promptly. Antivirals appears to have not had any major adverse effects. More data from different regions and large samples are needed to illuminate the characteristics of children with novel influenza A (H1N1) virus infection.</p>

Relationship between interleukin-12B gene + 1188 polymorphism and the susceptibility to hepatitis B virus intrauterine infection / 中华传染病杂志

10 mU/L (GroupⅡ,71 cases) when they were one year old.There were 40 healthy children in control group. The genomic DNA from the peripheral blood was extracted and polymerase chain reaction (PCR) and sequencing were employed to detect the IL-12B gene 3′UTR+1188 SNP.Results The frequency of AA,AC and CC genotype in GroupⅠwere 25.7%,44.3% and 30.0% respectively,and 36.6%, 47.9% and 15.5% in GroupⅡ,48.8%,39.0%,12.2%,in control group,respectively.The differ- ence of frequency of CC genotype and non-CC genotype between GroupⅠand GroupⅡwas significant (x~2=17.078,P

Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection.</p><p><b>METHODS</b>This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group I); and immune effective group (group II) and non high risk children belonged to the control group. Four gene SNP sites of TNF-alpha -238, IFN-gamma +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR).</p><p><b>RESULTS</b>The significant differences of TNF-alpha -238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) and between group I and the control group (chi(2) = 9.513, P < 0.05). No evident differences of TNF-alpha -238 A were found between group II and control group (chi(2) = 0.047, P > 0.05); the significant differences of IFN-gamma +874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the control group (chi(2) = 5.199, P < 0.05). No evident differences were found between group II and the control group (chi(2) = 0.602, P > 0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), also group I and the control group (chi(2) = 0.584, P > 0.05), and the group II and the control group (chi(2) = 0.004, P > 0.05) respectively; The significant differences of IL-10 -1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but the significant differences were not found between group I and the control group (chi(2) = 1.759, P > 0.05).</p><p><b>CONCLUSIONS</b>This study suggested the possibility that the TNF-alpha -238 A allele and IFN-gamma +874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection.</p>

The protective role of hyperoxic Ringer's solution on the hepatic injury in rats with burn shock / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the dynamic postburn changes in rat hepatic function and the effects of hyperoxic Ringer's solution resuscitation on the function.</p><p><b>METHODS</b>One hundred and ninety Wistar rats of both sexes with body weight of 250 - 300 g were employed as the model and were divided into 6 groups as A, B, C, D, E and F groups as follows: normal control (A, n = 10), early resuscitation with Ringer's solution (B, n = 40), delayed resuscitation with Ringer's solution (C, n = 30), early resuscitation with hyperoxic Ringer's solution (D, n = 40), delayed hyperoxic Ringer's solution resuscitation (E, n = 30) and burn control (F, n = 40). Blood samples were drawn from the injured rats under anesthesia at 6, 12, 24 and 48 postburn hours (PBHs), and the serum contents of ALT, AST and MDA in these blood samples were determined. Hepatic tissue samples were also harvested at the same time and served histologically.</p><p><b>RESULTS</b>The plasma ALT level at 6 PBH in all groups was higher than that in A group (P < 0.05). There was significant difference of plasma ALT levels between hyperoxic Ringer's solution treatment group an other treatment groups (P < 0.05). And there was evident difference of plasma ALT levels between hyperoxic Ringer's solution treatment groups and other treatment groups (P < 0.05). The dynamic change in plasma AST was almost similar to that of ALT. The plasma MDA level was increased obviously after injury, especially in F group (highest level). Furthermore, the MDA level in C group was higher than that in B group. The plasma MDA levels in D and E groups were evidently lower than that in all other groups (P < 0.05). It was revealed by histological examination that there were different degrees of degeneration an necrosis of hepatocytes during early postburn stage, but less so in D group.</p><p><b>CONCLUSION</b>Fluid resuscitation during early postburn stage with hyperoxic Ringer's solution could inhibit the production of oxygen free radicals and blunt lipid peroxidation, and it could also enhance the host tolerance to hypoxia and prevent hepatocytes from injury, thus hepatic function was protected.</p>