Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Clinical epidemiology and disease burden of bronchiolitis in hospitalized children in China: a national cross-sectional study.

BACKGROUND: Bronchiolitis is a common acute lower respiratory tract infection (ALRTI) and the most frequent cause of hospitalization of infants and young children with ALRTI. Respiratory syncytial virus is the main pathogen that leads to severe bronchiolitis. The disease burden is relatively high. To date, few descriptions of the clinical epidemiology and disease burden of children hospitalized for bronchiolitis are available. This study reports the general clinical epidemiological characteristics and disease burden of bronchiolitis in hospitalized children in China. METHODS: This study included the face sheet of discharge medical records collected from 27 tertiary children's hospitals from January 2016 to December 2020 that were aggregated into the FUTang Update medical REcords (FUTURE) database. The sociodemographic variables, length of stay (LOS) and disease burden of children with bronchiolitis were analyzed and compared using appropriate statistical tests. RESULTS: In total, 42,928 children aged 0-3 years were hospitalized due to bronchiolitis from January 2016 to December 2020, accounting for 1.5% of the total number of hospitalized children of the same age in the database during the period and 5.31% of the hospitalizations for ALRTI. The male to female ratio was 2.01:1. Meanwhile, more boys than girls were observed in different regions, age groups, years, and residences. The 1-2 year age group had the greatest number of hospitalizations for bronchiolitis, while the 29 days-6 months group had the largest proportion of the total inpatients and inpatients with ALRTI in the same age group. In terms of region, the hospitalization rate of bronchiolitis was the highest in East China. Overall, the number of hospitalizations from 2017 to 2020 showed a decreasing trend from that in 2016. Seasonally, the peak hospitalizations for bronchiolitis occurred in winter. Hospitalization rates in North China in autumn and winter were higher than those in South China, while hospitalization rates in South China were higher in spring and summer. Approximately, half of the patients with bronchiolitis had no complications. Among the complications, myocardial injury, abnormal liver function and diarrhea were more common. The median LOS was 6 days [interquartile range (IQR) = 5-8], and the median hospitalization cost was 758 United States dollars (IQR = 601.96-1029.53). CONCLUSIONS: Bronchiolitis is a common respiratory disease in infants and young children in China, and it accounts for a higher proportion of both total hospitalizations and hospitalizations due to ALRTI in children. Among them, children aged 29 days-2 years are the main hospitalized population, and the hospitalization rate of boys is significantly higher than that of girls. The peak season for bronchiolitis is winter. Bronchiolitis causes few complications and has a low mortality rate, but the burden of this disease is heavy.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Comparison between hospital- and community-acquired septic shock in children: a single-center retrospective cohort study.

BACKGROUND: We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). METHODS: This retrospective study enrolled children with septic shock at the PICU of Beijing Children's Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality. RESULTS: A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively (P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992-1.000, P = 0.028], positive pathogen detection (OR = 3.557, 95% CI = 1.307-9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95% CI = 1.974-60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022-1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806-36.465, P = 0.006) were risk factors for 28-day mortality in patients with CASS. CONCLUSIONS: The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Complete Genome Sequence Analysis of Echovirus 18 Associated with Aseptic Meningitis in Hebei Province, China, in 2015.

Echovirus 18 is a member of the genus Enterovirus, family Picornaviridae, which can cause meningitis in children. Here, we report the echovirus 18 complete genome sequence, which was isolated from the cerebrospinal fluid of a child with aseptic meningitis in Hebei Province, China.

[Characterization of BZLF1 gene and its promoter Zp of EBV strains in children with EBV-associated diseases in recent 5 years in Beijing area].

This study aims to investigate the genetic characteristics of BZLF1 gene and its promoter Zp of the epidemic strains in children with primary Epstein-Barr virus (EBV)-associated diseases. Total DNA was extracted from the peripheral blood of 134 children with EBV-associated infectious mononucleosis (EBV-IM) and 32 children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) who were admitted to Beijing Children's Hospital from 2006 to 2011. The EBNA3C, BZLF1, and Zp genes were amplified by PCR assay. Typing of EBV was performed according to the size of the amplification product of EBNA3C gene; the amplification products of BZLF1 and Zp genes were subjected to direct sequencing, and sequence analysis was performed using BioEdit 7. 0. 9. The results were as follows: (1) EBV-1 was present in 140 samples (97.2%, 140/144) and EBV-II in 4 samples (2.8%, 4/144). (2) Three BZLF1 genotypes and their 12 subtypes (including 6 newly found subtypes) were detected in this study; there were no significant differences in the frequencies of BZLF1-A and BZLF1-B between the children with EBV-IM and EBV-HLH (P = 0.083); BZLF1-A1 was the dominant genotype in children with EBV-associated diseases; t BZLF1-A mostly had three 29-bp repeats in the first intron of BZLF1 gene, and BZLF1-B mostly had 30-bp repeats (P = 0.000), with the number of repeats varying from 1 to 13. (3) Four Zp genotypes were detected in this study, including Zp-P, Zp-V3, Zp-V4, and Zp-V1; there were no significant differences in the frequencies of these Zp genotypes between children with EBV-IM and EBV-HLH (P = 0.272, 0.252, 1.0, and 1.0, respectively). (4) The linkage analysis of BZLF1 gene and its promoter Zp showed that BZLF1-A1 was highly associated with Zp-V3 (P = 0.000), while BZLF1-B4 with Zp-P (P = 0.000); EBV-I + BZLF1 A1 was highly associated with Zp-V3 (P = 0.000), while EBV-I+BZLF1-B4 with Zp-P (P = 0.000). The conclusions are as follows: (1) BZLF1-A1 is the dominant genotype in children with EBV-associated diseases; there are mostly 29-bp repeats in the first intron of BZLF1 gene for BZLF1-A genotype and 30-bp repeats for BZLF1-B genotype. (2) Zp-P and Zp-V3 are dominant Zp genotypes of EBV in children, which shared similar detection rates. (3) BZLF1-A1 is highly associated with Zp-V3, while BZLF1-B4 with Zp-P; EBV-I+BZLF1-A1 is highly associated with Zp-V3, while EBV-I+BZLF1-B4 with Zp-P.

[Viral etiology of acute respiratory tract infection among pediatric inpatients and outpatients from 2010 to 2012 in Beijing, China].

OBJECTIVE: Acute respiratory tract infections (ARI) are the leading cause of pediatric morbidity and mortality worldwide, particularly in developing countries. Viruses are the main pathogens of ARI in children. The purpose of the present study was to determine the epidemiologic features of respiratory viruses, including novel viruses, in outpatient and hospitalized children with ARI. METHOD: From March 2010 to February 2012, 2066 children with ARI, including 1050 outpatients and 1016 inpatients, were involved in this study. One nasopharyngeal aspirate or throat swab specimen was collected from each patient. Reverse transcription (RT) PCRs were performed to detect common respiratory tract viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumonia virus (HMPV) and human bocavirus (HBOV). RESULT: At least one viral pathogen was identified in each of 1274 out of 2066 patients and the overall positive rate was 61.7%. The positive rate in inpatient (69.7%) was higher than that in outpatient (53.9%). The frequencies of detection of various viruses among in- and outpatients were different. RSV was the most prevalent virus detected among hospitalized children, followed by HRV and PIV, whereas IFV was the most frequently identified virus in the outpatient group, followed by ADV and PIV. Simultaneous detection of two or more viruses was found in 377 cases. Coinfection was more frequent in inpatients than in outpatients (30.1% vs. 6.8%, P < 0.001). CONCLUSION: Respiratory viruses play an important role in children with ARI, especially in young children. RSV was the most prevalent virus detected among hospitalized children, whereas IFV was the most frequently identified virus in the outpatient group. Viral coinfections are frequently identified, particularly in hospitalized patients. Further studies are required to better understand the impact of coinfections in children with ARI.

[Characteristic of nuclear antigen 1 gene and latent membrane protein 1 gene of Epstein-Barr virus in primary EBV infection in children in Beijing area in 2005-2010].

OBJECTIVE: To analyze the characteristic of nuclear antigen 1 gene and latent membrane protein 1 gene of Epstein-Barr virus in primary EBV infection in children in Beijing area in 2005-2012. METHODS: Polymerase chain reaction (PCR) was used to amplify the EBNA-3C, EBNA1 and LMP1 genes. The amplified products were sequenced directly and the sequences were analyzed by BioEdit 7. 0. 9 and MEGA 4. 0. 2. RESULTS: Type A EBV was detected in 98% samples. Nucleotide sequence analysis of the carboxy-terminal region of EBNA1 showed that Vvvl was deteted in 98% samples. DNA sequence analysis of LMP1 C-terminus indicated that China 1 was 90% in this study. There were no significant differences in the frequency of Vvv1 and China 1 between the IM and HLH samples (P = 1.00). Linkage analysis of EBV types, EBNA1 and LMP1 variants indicated that 90% of EBV type A was associated with EBNA1-Vvv1 variant and LMP1-China 1 variant in 40 cases. Full length of LMP1 gene was successfully amplified in 35 cases. Four Chinese groups (CG1-4) were identified. The percentage of CG1-CG4 were 85%, 6%, 6% and 3%, respectively. CONCLUSION: EBV type A is predominant in primary EBV infection in children in Beijing Area. EBNA1-Vvv1 and LMP1-China 1 variants were predominant genotypes in this area. There is a high linkage between EBNA1-Vvv1 variant and LMP1-China 1 variant. Four Chinese groups (CG1-4) were identified according to the full length of LMP1 gene and CG1 was the most prevalent.

[Simultaneous detection of human parainfluenza viruses 1, 2, 3 by multiplex real-time reverse transcription-polymerase chain reaction with LNA probes].

OBJECTIVE: Human parainfluenza virus (HPIV) types 1, 2 and 3 are major viral pathogens responsible for upper and lower respiratory tract infections. In this study, a real-time RT-PCR was developed using multiplex primers-probe (HPIV-1, 2, 3) for the simultaneous detection of both HPIV1, HPIV2 and HPIV3 genomes. METHODS: Optimal primers and probes were designed using specialized software. The conditions for multiplex real-time RT-PCR had been optimized. The synthesis of RNA standards of HPIV1, 2, 3 were used a T7 RNA polymerase. Check the specificity sensitivities and stability of one step RT-PCR assay. RESULTS: Obtained in a 10-fold dilution series assay demonstrate a high sensitivity of the assay with a lowest detection limit of 10 copies for HPIV1, 100 copies for HPIV2 and 100 copies for HPIV3. CONCLUSION: The assays demonstrates an improved sensitivity and scope of detecting HPIV1, 2, 3 viruses relative to routine antigen detection assays while the quantitative utility may facilitate investigation of the pre-diagnosis and respiratory virus pathogenesis.

Epidemiologic and clinical characteristics of infectious mononucleosis associated with Epstein-Barr virus infection in children in Beijing, China.

BACKGROUND: infectious mononucleosis (IM) is a self-limited disease, but a few cases may have severe complications. This retrospective study was to explore the epidemiologic and clinical characteristics of IM associated with Epstein-Barr virus infection (EBV-IM) in children. METHODS: hospitalized patients with EBV-IM were enrolled during January 2005 to October 2008 in Beijing Children's Hospital Affi liated to Capital Medical University. All patients were divided into four groups: <1 year (group I), 1 to 3 years (group II), 3 to 6 years (group III), and ≥ 6 years (group IV). The epidemiology and clinical characteristics were compared among the four groups. RESULTS: totally 418 patients were enrolled, with 245 boys and 173 girls. Fever, lymphadenopathy and pharyngitis were three main manifestations of the patients. The incidences of hepatomegaly, splenomegaly and rash were higher in the patients aged below 6 years, and with age increment the incidences lowered. In contrast, the patients aged <1 year had the lowest incidence of tonsillopharyngitis. The total white blood cell count was higher in the infantile group than in the other groups (P=0.038). The infantile group had significantly lower levels of serum alanine aminotransferase and aspartate aminotransferase than the older groups (P=0.007 and P=0.012 respectively). The percentage of CD4(+) T cell subset decreased and the percentage of CD8(+) T cell subset increased with age increment. CONCLUSIONS: the incidence of EBV-IM peaked in children at age of 4 to 6 years in Northern China. Most of the patients had the classic triad of fever, lymphadenopathy and pharyngitis. Clinical symptoms, signs, laboratory findings and complications of patients varied with ages.

[Three years surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010].

OBJECTIVE: Viruses are common pathogens of acute lower respiratory tract infection (ALRTI) in children. There are few studies on consecutive monitoring of viral pathogens of ALRTI in a larger cohort during the past several years. The aim of this study was to investigate the viral pathogens of ALRTI in children of different age groups and to outline the epidemic feature of different viruses. METHOD: (1) Totally 1914 (1281 male and 709 female) children with clinical diagnosis of ALRTI during the period of March 2007 to March 2010 were recruited into this study. These patients were hospitalized patients in department of internal medicine or outpatients in emergency department in Beijing Children's Hospital. The patients were divided into four groups, including 1072 patients < 1 year old, 326 patients 1- < 3 years old, 158 patients 3- < 6 years old, 358 patients ≥ 6 years old. One nasopharyngeal aspirate specimen was collected from each patient. Reverse transcription (RT) PCR methods were applied to detect common respiratory viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus type A, B and C (IFA, IFB, IFC), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumovirus (HMPV) and human bocavirus (HBOV). RESULT: (1) The total positive rate of viruses was 70.3%. The positive rate was 83.0% (890/1072) in the group of < 1 year old, and 80.1% (261/326) in group of 1- < 3 years old, 60.8% (96/158) in group of 3- < 6 years old and 27.7% (99/358) in group of ≥ 6 years old, respectively. There was a significant difference in the positive rate among different age groups (χ² = 2213.5, P = 0.000). The top three viruses were RSV, HRV and PIV; and the positive rates were 50.9%, 36.2% and 12.0% respectively in group of < 1 year old. (2) The epidemic seasons of RSV and HRV were winter and spring, and PIV infection was epidemic in spring and summer. (3) The detection rates of 2 or more viruses were 38.2%, 36.4%, 30.2% and 15.2% in groups of < 1 year old, 1- < 3 years old, 3- < 6 years old and ≥ 6 years old, respectively. There was a significant difference in the mixed infection rate among different age groups (χ² = 1346.00, P = 0.000). CONCLUSION: RSV, HRV and PIV were the most predominant pathogens in younger children with ALRTI. Different viral infections had different seasonal features. Mixed infections with two or more viruses were detected in substantial proportion of patients with ALRTI, but further studies are needed to explore the clinical significance of mixed infection with viruses in patients with ALRTI.

Human Coronaviruses HCoV-NL63 and HCoV-HKU1 in Hospitalized Children with Acute Respiratory Infections in Beijing, China.

The human coronaviruses (HCoVs) HCoV-NL63 and HCoV-HKU1 are two recently discovered coronaviruses that circulate widely and are associated with acute respiratory infections (ARI). We detected HCoV-NL63 and HCoV-HKU1 in specimens collected from May 2008 to March 2010 from patients with ARI aged <7.75 years of age attending the Beijing Children's Hospital. Thirty-two (8.4%) and 57 (14.9%) of 382 specimens tested positive for HCoV-NL63 and HCoV-HKU1, respectively, by real-time RT-PCR. Use of a Luminex xTAG RVP Fast kit showed that coinfection with respiratory syncytial virus and parainfluenza 3 virus was common among patients infected with either virus type. In HCoV-HKU1-infected patients, the predominant clinical symptoms were cough, fever, and expectoration. In HCoV-NL63-infected patients they were cough, fever, and rhinorrhea. Phylogenetic studies showed that the HCoV-HKU1 nucleoprotein gene was relatively conserved compared to NCBI reference sequences, while the 1ab gene of HCoV-NL63 showed more variation.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: a retrospective study of 78 pediatric cases in mainland of China.

BACKGROUND: The clinical characteristics of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are largely unreported in the pediatric patients in mainland of China. The main aim of this study was to recognize the clinical features of EBV-HLH in children and to explore its prognosis and risk factors. METHODS: A retrospective study was performed on 78 pediatric patients with EBV-HLH who were admitted to Beijing Children's Hospital between 2003 and 2008. All patients' medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory and outcome information was collected. Statistical analysis was conducted via multivariate and univariate analysis. RESULTS: The age of onset peaked between 1 - 2 years and boys were more likely developed EBV-HLH. EBV-HLH occurred mainly in the serological pattern with EBV nuclear antigen (EBNA) positive (70.5%). The overall fatality of the disease was 56.7%. Twelve of the 39 fatalities (30.8%) died rapidly within 2 months after diagnosis. Multivariate analysis revealed that not receiving chemotherapy (P = 0.002), > or = 4 weeks of illness prior to diagnosis (P = 0.004), and albumin levels < 20 g/L (P = 0.045) significantly predicted an increased fatality risk. CONCLUSIONS: EBV-HLH is a severe disease with a high fatality rate that occurs mainly in the serological pattern with EBNA positive. Early initiation of chemotherapy and timely diagnosis significantly improves survival rate. Practical strategies should focus on reducing the likelihood of early death.

[Clinical analysis and follow-up study of Epstein-Barr virus associated-hemophagocytic lymphohistiocytosis in childhood].

OBJECTIVE: To identify the clinical characteristics of and to explore the prognostic factors influencing mortality in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). METHOD: A retrospective study was conducted on 62 pediatric patients with EBV-HLH who were admitted to our hospital between 2003 and 2008. All their medical records were reviewed and analyzed. For each patient, demographic, clinical and laboratory data, genetic findings and outcome information were collected. The patients were divided into two groups: deceased or survived based on the follow-up results. Comparative analysis of the data was done by using independent-samples t test and Logistic multiple and univariate regression. RESULT: (1) Among the 62 EBV-HLH patients, 36 were male and 26 were female. The age of onset ranged from 2 months to 14 years and most of the patients were between 1 and 3 years of age. EBV-HLH occurred mainly in the setting of reactivation (61.3%). (2) All patients exhibited persistent or intermittent fever and cytopenia >/= 2 cell lines. Most of the patients presented with hepatomegaly (83.9%), splenomegaly (72.6%) and lymphadenopathy (69.4%). The main laboratory features showed an elevation of serum ferritin and aminotransferase levels. A reduction in serum albumin was observed and exhibited coagulopathy with hypofibrinogenemia and hypertriglyceridemia in most of the patients. Forty-eight of patients had hemophagocytosis in bone marrow at diagnosis of EBV-HLH. The serum EBV DNA level in 14 of 31 patients with EBV-HLH was in the range of 5.12 x 10(2) - 7.69 x 10(7) copies/ml with a mean value of 10(3.9) copies/ml. (3) Three heterozygous mutations in coding region were found, which resulted in amino acid change (C102F, S108N and T450M) in 3 patients. One patient had compound heterozygous mutations (S108N and T450M) in the PRF1 gene as the background defect and documented familial HLH type 2 (FHL2). (4) During the observational period, 35 of 57 patients (61.4%) died 3 months to 3 years after the onset, while 21 of whom died despite aggressive polychemotherapy, 15 of whom died within 2 months after hospitalization. The deceased patients were more likely to have lower albumin level and more prolonged activated partial thromboplastin time than the survived patients (P < 0.05 for all comparisons). Multivariate Logistic regression analysis revealed that duration of illness >/= 1 month, non-chemotherapy, albumin level < / = 25 microg/L and internal organs hemorrhage were related with the prognosis significantly (P < 0.05 for all comparisons). CONCLUSION: This study revealed that EBV-HLH infection in pediatric patients had severe clinical courses and prognosis was poor and the majority of cases underwent EBV reactivation. The early diagnosis, prompt and proper chemotherapy can improve the survival rate. The duration of illness >/= 1 month, non-chemotherapy, decreases in albumin and internal organs hemorrhage were the risk factors related to mortality in children with EBV-HLH.

[Incidence and relationship of human cytomegalovirus infection and human herpesvirus 6 infection in pediatric patients after hemopoietic stem cell transplantation].

OBJECTIVE: To study the incidence of human cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) infection in pediatric patients with hemopoietic stem cell transplantation (HSCT), and to explore the relationship between CMV and HHV-6 infection in pediatric patients with HSCT. METHODS: Pediatric patients with HSCT in hemotology center of Beijing Children's Hospital were enrolled into this study from June 2007 to October 2009. Peripheral blood were collected every week after HSCT, and Fluorescent quantitation PCR and conventional PCR were used to detect CMV DNA load in serum and HHV-6 DNA in peripheral blood respectively. Genetic typing was conducted on HHV-6. RESULTS: Fifty two pediatric patients with HSCT were enrolled into this study, and six hundreds and thirty six specimens were collected totally. CMV DNA was detected in fifty two specimens from twenty cases. The median time was 56 days after HSCT. The incidence of CMV infection was 38.5% (20/52) in all HSCT patients and 47.6% (20/42) in allogene HSCT patients. The incidence of late CMV infection was 22.2% (6/27) in allogene HSCT. Three patients died of CMV infection,and two died of CMV interstitial pneumonia. HHV-6 DNA was detected in thirty three specimens from fourteen cases. The median time was 23 days after HSCT. The incidence of HHV-6 infection was 26.9% (14/52)in all HSCT patients and 31% (13/42) in allogene HSCT patients. The genotype of HHV6 was all type B. HHV-6 DNA was positive in six of twenty cases with CMV infection. The incidence of co-infection was 30% (6/20). CONCLUSIONS: There was a substantial incidence of CMV and HHV6 infection after HSCT. The relationship between earlier HHV6 infection and later CMV infection in pediatric patients with HSCT need further study.