[Analysis on clinical and epidemioloical characteristics of measles in hospitalized children in Shanghai in 2012].

OBJECTIVE: To investigate the main factors that influence measles morbidity and the genotype of measles virus, so as to provide evidence for scientific decision making to further control the prevalence of measles. METHOD: A retrospective analysis included 182 children in Children's Hospital of Fudan University, diagnosed with measles from January 1, 2012 to December 31. The clinical and epidemiological characteristics, including the gender, age, the incidence of seasonal trends, measles vaccine vaccination history, contact history and other clinical manifestations, laboratory test results, and so on were analyzed. And the reverse transcription PCR (RT-PCR) was adopted to detect sputum specimens from suspected patients with measles,who were selected randomly,the sequence of the part of the PCR products was analyzed. RESULT: (1) Clinical and epidemiological data: Totally were 182 children with measles (125 males, 57 females) were enrolled into this study. The age of the patients ranged from 3 months to 89 months, 127 cases were younger than 9 months (69. 8%). The prevalence season was from April to August, while the peak month was April and May (22. 5%, 23. 1%). Among 182 hospitalized children, only 11 cases underwent measles vaccination (6. 0%), and among them 5 cases were within 2 weeks before disease onset. A total of 167 cases (91. 8%) had not been vaccinated, most of whom were immigrants, and the measles vaccination history of the remaining 4 cases were unknown. There was a positive correlation between the measles vaccination ratio in children of the floating population (8. 45%, 6/71) and the settled children (29.4%, 5/17, χ =8. 11 P =0. 004). In total, 24 cases (13. 2%) had definite measles exposure history, with 153 cases (84. 1%) of unknown origin,5 cases (2.7%) without any history of contact. (2) Clinical manifestations: All the 182 patients had fever (100%) and obvious rashes (100%), among them 145 cases had body temperature higher than 39 °C (79. 7%). The fever period ranged from 2 to 38 days. Among 182 hospitalized children,165 cases (90. 7%) had typical measles,17 cases had atypical measles. Among the 17 cases, two had severe measles, one had heterotypic measles. (3) The common complica tions: 96 cases had pneumonia (52. 8%), 80 had laryngitis (44. 0%), 38 had bronchitis (20. 9%),15 had hepatic dysfunction (8. 2%), 11 had myocardial damage (6. 0%), 3 had febrile seizures (1. 6%), and no patient had encephalitis. Of the 96 cases with pneumonia, 92 received sputum test; 38 were sputum culture positive (41%). The dominant pathogens were Streptococcus pneumoniae(11/38,29%), Haemophilus influenzae (6/ 38,16%), Moraxella catarrhalis (4/38, 11%), Escherichia coli (4/38, 11%), Candida albicans (4/38, 11%), Mycoplasma pneumoniae (4/38, 11%) and Staphylococcus aureus (3/38, 8%). (4) The H1a genotype was the only one genotype in the detected sequence of 54 measles virus strains. CONCLUSION: Measles was more often seen in the children under the age of 9 months from the floating population. The morbidity peak month was from April to May in Shanghai. The H1a genotype was the only one genotype. We should try to improve vaccination coverage rate in the children who are at the age for vaccination, so as to prevent measles outbreak.

The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010.

BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.

[The first confirmed pediatric case with H7N9 avian influenza virus infection in China].

OBJECTIVE: To understand the clinical and epidemiological aspects of avian influenza A (H7N9) virus infection in children. METHOD: 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. RESULT: 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. CONCLUSION: 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.

Children of rural-to-urban migrant workers in China are at a higher risk of contracting severe hand, foot and mouth disease and EV71 infection: a hospital-based study.

The incidence and severity of hand, foot and mouth disease have increased in mainland China since 2008. Therapies and vaccines are currently at different stages of development. This study aimed to determine the social factors associated with the outbreaks and severity of the disease in Chinese children. A multicentre, prospective, case-controlled study was conducted in Shanghai, Chongqing, Guangzhou and Shantou to identify the sociodemographic and behavioural risk factors for hand, foot and mouth disease. Children hospitalized for hand, foot and mouth disease were randomly enrolled from April to November 2011. Stool samples were collected to test for the presence of enterovirus 71 (EV71). A total of 443 children between 1.6 and 68 months of age were enrolled; 304 were uncomplicated cases and 139 were severe cases with central nervous system involvement. The overall detection rate of EV71 was 54.2%, and the positivity rate of EV71 was significantly higher in the severe group than in the uncomplicated group (82.0% versus 40.9%, odds ratio (OR): 8.35, P=0.000). The children of migrant workers (OR: 3.014, P=0.000) and children attending kindergarten (OR: 2.133, P=0.002) were significantly associated with a severe outcome of the disease (OR: 1.765, P=0.026). Our findings indicate that kindergarten attendance and migrant worker parents are the major risk factors associated with severe hand, foot and mouth disease in children <5 years of age. Future public health intervention vaccination campaigns should consider the particular difficulties of achieving high compliance with multiple-dose vaccination regimens in the children of migrant workers.

[Profiles of innate immune receptors and cytokines in peripheral blood mononuclear cells in children with measles].

OBJECTIVE: The aim of this study was to explore the roles and clinical significance of innate immune receptors and cytokine in children with measles. METHOD: 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/ß and IL-10 in peripheral blood mononuclear cells were detected by real-time PCR. The protein levels of IFN-α, IFN-ß and IL-10 in plasma were measured using ELISA. SPSS 13.0 software was applied to analyze the difference between two groups. RESULT: 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-ß 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). CONCLUSION: 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.

Seroepidemiology of Enterovirus 71 infection prior to the 2011 season in children in Shanghai.

BACKGROUND: In 2010, China experienced the largest outbreak on record of Enterovirus 71 (EV71)-associated Hand Foot and Mouth Disease (HFMD) with more than 1.7 million cases, 27,000 patients with severe neurological complications and 905 deaths. Understanding of the seroprevalence of neutralizing antibodies (NAb) against EV71 and their protective role against HFMD in children is crucial for the implementation of future therapeutic and prophylactic intervention. OBJECTIVES: To correlate the prevalence of NAb against EV71 genotype C4a in children prior to the 2011 epidemic season with severe EV71-associated HFMD disease during the subsequent 2011 epidemic season. STUDY DESIGN: 614 sera samples were collected from children without HFMD. EV71 NAb were tested by a quantitative PCR assay. Samples with NAb ≥1:8 were scored as positive. RESULTS: 122 (19.9%) of 614 sera were EV71-seropositive. The NAb seroprevalence was highest in infants 0-5 months of age (28.6%) and lowest in children 1-1.9 years of age (13.4%). 64.1% of severe EV71-associated HFMD occurred in children 1-2.9 years. CONCLUSIONS: Despite the large 2010 outbreak, the overall seroprevalence of EV71 in children is relatively low. The seropositive rate of EV71 NAb prior to the 2011 season was inversely correlated with the number of EV71-infected severe cases in 2011. Loss of maternal antibodies in infants and lack of acquired anti-EV71 immunity are responsible for increased proportion of severe HFMD in the 1-2 years age group. Our data suggest that future vaccination campaigns should be initiated as early as 6 months.

[Association of interferon-gamma + 874 gene single nucleotide polymorphism with susceptibility to intrauterine HBV infection].

OBJECTIVE: To explore the susceptibility of children to develop intrauterine hepatitis B virus (HBV) infection through studying the association between interferon gamma (IFN-gamma) + 874 single nucleotide polymorphism (SNP) and intrauterine HBV infection. METHODS: The subjects were selected from outpatients who were in our hepatitis B (HB) vaccine following-up clinics. The subjects whose mothers were HBV carriers were inoculated with HB vaccine or HB vaccine and hepatitis B immunoglobulin (HBIg). Intrauterine HBV infection was defined as peripheral blood HBsAg and/or HBV-DNA positive at birth and lasting for six months (group I). Normal immune children were defined as peripheral blood negative for HBV marker since birth and afterwards HBsAb titers were above protective level (group II). The subjects were composed of the following two groups. Group I consisted of 46 children with intrauterine HBV infection. Group II was composed of 73 normal children. A Taqman fluorescence polymerase chain reaction for the IFN-gamma + 874 SNP was performed for both groups. RESULTS: IFN-gamma + 874 SNP was tested successfully for every subject. Frequencies of AA, AT and TT genotype were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group. A significant difference was found in the frequency distribution of IFN-gamma + 874 genotype between the two groups (chi(2) = 5.102, P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in normal immune group. CONCLUSION: There is an association between IFN-gamma + 874 SNP and intrauterine HBV infection. This study suggested the possibility that IFN-gamma + 874 SNP might be important in determining an individual's susceptibility to development of intrauterine HBV infection.