Epidemiological characteristics and spatial epidemiology of hand-foot-mouth disease in Hunan Province, China, from 2008 to 2019 / 中国当代儿科杂志

OBJECTIVES@#To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province.@*METHODS@#Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019.@*RESULTS@#The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019.@*CONCLUSIONS@#The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.

Cross-neutralizing Anti-hemagglutinin Antibodies Isolated from Patients Infected with Avian Influenza A (H5N1) Virus / 生物医学与环境科学（英文）

Objective@#To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features.@*Methods@#We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients. The genetic basis, biological functions, and epitopes of the obtained BnAbs were assessed and modeled.@*Results@#Two BnAbs, 2-12D5, and 3-37G7.1, were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset. Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity (ADCC) activity. Albeit derived from distinct Ab lineages, , V 1-69-D2-15-J 4 (2-12D5) and V 1-2-D3-9-J 5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V 1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively.@*Conclusions@#Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus. The HA stem epitopes targeted by the BnAbs, and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.

Virological surveillance of pandemic (H1N1) 2009 virus and its genetic characteristics in Hunan Province, 2009-2011 / 病毒学报

To understand and master the dynamic variation of the pandemic influenza A (H1N1) 2009 in Hunan province from 2009 to 2011, and to know the genetic characteristics and drug resistance of the pandemic (H1N1) 2009 viruses. Throat swab specimens of influenza-like illness patients were collected from sentinel hospitals and tested for influenza by fluorescent PCR or virus isolation methods. Partial isolates were selected for sequencing. The sequences were used for phylogenetic analysis by MEGA 5. 05 software. From the 20th week of 2009 to the 52nd week of 2011, 17 773 specimens were tested. 3 831 specimens were influenza-positive with a positive rate of 21. 6%, of which 1 794 were positive specimens of pandemic (H1N1) 2009, accounting for 46. 8%00 of the influenza-positives. There were 2 epidemic peaks of pandemic (H1N1) 2009, which were in the 41st-53rd week of 2009 and the 1st-12nd week of 2011, respectively. The HA genes of 23 strains that were selected for sequencing had close relationship; the distribution of strains in the phylogenetic tree was basically in chronological order. The complete genome sequence analysis showed that all of 8 gene segments of 7 strains were homologous to the vaccine strain, and there was no gene reassortment. The HA amino acid sites of the 23 strains were highly similar to the vaccine strain (98. 2% - 100. 0% in homology), but all 23 strains had P83S, S203T and 1321V mutations. The 222 site mutation that may lead to enhanced virulence was found in the A/Hunan/YQ30/2009 strain. The mutation was D222E. There was no oseltamivir resistance mutation found in all strains. The pandemic (H1N1) 2009 in Hunan province from 2009 to 2011 had a bimodal distribution. There was no large-scale variation of virus genes. The clinical use of oseltamivir was still effective. Key words: Pandemic (H1N1) 2009; Surveillance; Genetic characteristics

The influence of familial factors on post rabies exposure vaccination in rural habitants / 中华流行病学杂志

Objective To understand the current situation of potential exposure to rabies among the rural habitants in Hunan province,and to study the impact related to familial factors on post rabies exposure vaccination.Methods In total,40 villages from 20 townships of 4 counties were selected by multistage sampling method.Study samples were selected from these villagers and familial basic information and vaccination post rabies exposures were recorded through questionnaires.Data were statistically analyzed by SPSS 17.0.Results Among 3042 villagers from 864 households being surveyed,124 person-time exposures were found from January,2009 to October,2010,with a total exposure rate as 4.08％,and the annual average exposure rate as 2.33％.Data from univariante analysis showed that the rates on post rabies exposure vaccination were statistically correlated with the following four factors:knowledge on the score of rabies prevention (x2 =8.260,P =0.042),whether being involved in the new type of rural cooperative medical care (P =0.035),family disposable cash income in the year of 2009 (x2 =10.831,P =0.031),distance between the households and the health facilities in towns and townships (x2 =9.071,P=0.033).Results from logistic regression analysis indicated that the score of knowledge on rabies prevention (OR=1.420,95％CI:1.055-1.905) and the annual disposable cash income of the family in 2009 (OR=1.480,95％ CI:1.044-2.098) were independent factors that influencing the rabies vaccination.Conclusion Strengthening the education programs on rabies prevention in rural habitants and increasing family income were feasible way to increase the rate of rabies vaccination in rural areas of Hunan province.

Analysis of genetic features of influenza B virus in Hunan province from 2007 to 2010 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the gene variations of influenza B virus isolated in Hunan province from 2007 to 2010.</p><p><b>METHODS</b>A total of 42 strains of influenza B virus,which were isolated in the Influenza Surveillance Network Laboratories in Hunan province between year 2007 and 2010, were selected for the study. The hemagglutinin 1 (HA1) and neuraminidase (NA) genes of the selected strains were amplified by RT-PCR, and the sequence of the purified product were detected and homologically compared with the sequence of influenza vaccine strains isolated from Northern Hemisphere by WHO during the same period. In addition, the phylogenetic trees were constructed to characterize the molecular features.</p><p><b>RESULTS</b>In the Victoria branch of the HA1 gene phylogenetic tree, the strains isolated from year 2007 to 2009 were included in the V1 sub-branch, as well as the vaccine strain Malaysia/2506/2004; the strains isolated in year 2010 were involved in the V2 sub-branch, similar to the vaccine strains Brisbane/60/2008. In the Yamagata branch,the strains isolated in year 2007 were in the Y1 sub-branch,different from the strains isolated between year 2008 and 2010, which were in the Y2 sub-branch, instead. All virus in NA gene phylogenetic tree were included in the Yamagata branch, indicated their Yamagata origin. The genetic sequence analysis of the 7 strains isolated in year 2010 revealed that the viruses were classified as genotype 2 and genotype 15. The results of homological comparison between HA1 molecule and the influenza vaccine strains recommended by WHO were as below: Victoria lineage, 98.6% - 99.1% in 2007, 98.6% - 99.1% in 2008, 98.1% - 99.1% in 2009, and 97.6% - 99.1% in 2010; and Yamagata lineage, 97.9% - 98.5% in 2007, 97.9% - 98.5% in 2009 and 97.9% - 98.2% in 2010. The major mutations of the strains isolated in year 2007 were found in sites R48K, K88R, P108A, D197N and S230G. While the major mutations of the strains isolated between year 2009 and 2010 were sited in K88R, S150I, N166Y, D197N and S230G.</p><p><b>CONCLUSION</b>The prevalent influenza B virus isolated in Hunan province from 2007 to 2010 has mutated and evolved continuously.</p>

Risk factors of death cases of hand-foot-and-mouth disease in Hunan province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study risk factors of death cases of hand foot and mouth diseases (HFMD) in Hunan province, so as to provide scientific evidence for further prevention and control.</p><p><b>METHODS</b>The 105 death cases of HFMD between January and October, 2010 in Hunan Province were selected as case group; and the 210 survival cases of serious HFMD, which were matched by gender and resident places with a ratio at 2:1 in the same period in Hunan were selected as control group. The basic information, hospitalized experience and previous medical history had been surveyed and the relevant risk factors were analyzed by single factor and multi-factor logistic regression.</p><p><b>RESULTS</b>In case group, 79.05% (83/105) of the cases lived in rural area and 9.52% (10/105) of the cases lived in urban-rural midst area. In control group, 87.62% (184/210) of the cases lived in rural area and 11.43% (24/210) of the cases lived in urban-rural midst area. In case group, 59.05% (62/105) of the patients first visited rural (private) clinics and 20.00% (21/105) first visited community hospitals in villages and towns; while in control group, 43.81% (92/210) and 13.33% (28/210) chose rural (private) clinics and community hospitals in villages and towns as the first choice respectively.22.86% (24/105) of the case group and 39.05% (82/210) of the control group were diagnosed as HFMD in their first visit to hospital.27.62% (29/105) of the case group and 7.14% (15/210) in control group were provided pyrazolone in the treatment. For glucocorticoid, 80.95% (85/105) and 5.71% (6/105) of the case group were given as treatment by rural (private) clinics and community hospitals in villages and towns separately; while the proportions in the control group were 41.43% (87/210) and 0.48% (1/210) respectively. For antibiotics, 35.24% (37/105) and 23.81% (25/105) of the case group were prescribed by rural (private) clinics and community hospitals in villages and towns separately; while the percentages in the control group were 15.71% (33/210) and 7.14% (15/210). 3.81% (4/105) of the case group and 11.90% (25/210) of the control group were vaccinated in one month before the onset. The results of single-factor logistic regression indicated that living in rural areas (OR = 0.075, 95%CI: 0.016 - 0.343) and in rural-urban midst areas (OR = 0.069, 95%CI: 0.013 - 0.368), diagnosis of HFMD in the first visit to hospital (OR = 0.463, 95%CI: 0.271 - 0.788) and vaccination one month before the onset (OR = 0.293, 95%CI: 0.099 - 0.866) were four protective factors; while rural (private) clinics as the first choice (OR = 4.717, 95%CI: 1.891 - 11.767), community hospital in villages and towns as the first choice (OR = 5.250, 95%CI: 1.883 - 14.641), medication of pyrazolone (OR = 4.961, 95%CI: 2.520 - 9.766), medication of glucocorticoid in rural (private) clinics (OR = 6.009, 95%CI: 3.435 - 10.510) and in community hospital in villages and towns (OR = 12.667, 95%CI: 1.505 - 106.638), medication of antibiotics in rural (private) clinics (OR = 2.918, 95%CI: 1.690 - 5.040) and in community hospital in villages and towns (OR = 4.062, 95%CI: 2.036 - 8.108) were seven risk factors. The results of multi-factors logistic regression showed that medication of pyrazolone (OR = 2.311, 95%CI: 1.062 - 5.030), medication of glucocorticoid in rural (private) clinics (OR = 5.480, 95%CI: 3.039 - 9.880), medication of antibiotics in rural (private) clinics (OR = 2.430, 95%CI: 1.301 - 4.538) and medication of antibiotics in community hospitals in villages and towns (OR = 3.344, 95%CI: 1.477 - 7.569) were the risk factors of death of HFMD.</p><p><b>CONCLUSION</b>The risk factors of HFMD deaths include the medication of pyrazolone, glucocorticoid and antibiotics by rural (private) clinics and medical institutions in villages and towns. The department concerned should revise the technical manual to standardize the medication of the above drugs.</p>

Surveillance on the etiology and genetic characteristics of rabies in Hunan province, from 2008 to 2009 / 中华流行病学杂志

Objective To analyze the etiology of rabies in Hunan province and the genetic characteristics of rabies N gene isolated from 2008 to 2009.Methods Direct immunofluorescence assay (DFA) and nested PCR were employed to detect the monitoring samples including brain tissues of dogs and saliva,serum or urine which were collected in 2008 to 2009,from the rabies patients.Positive samples were sequenced by ABI3730 gene analyzer for the full length of the N gene target.The homology and hpylogeography of the rabies virus were analyzed after the phylogenetic tree was constructed by Blast,Clustal W and Mega 4.0 software.Results Of the 1451 tissue samples from the dogs' brain,31 were positive under DFA and the positive rate was 2.14％.The DFA positive samples were redeteeted by RT-PCR and the positive rate was 1.17％.56 samples of saliva,serum and urine samples were detected by RT-PCR from the rabies patients,with 3 positives and the positive rate was 5.36％.The length of nest PCR products were 255 bp.The rates of homology to the nucleotide and the amino acid of rabies N gene were 87.2％-87.9％ after compared to the pasture strain.The phylogenetic tree was successfully built and 20 strains isolated lately belonged to the rabies gene type Ⅰ.Conclusion The epidemic situation of human and dogs rabies in Human were relatively stable,with all the isolated rabies virus belonging to genotype Ⅰ,without any variation.

Serological survey of pandemic influenza A (H1N1) virus infection among population in Hunan Province / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To understand the infection condition and analytical methods of Influenza A (H1N1) virus in the population of Hunan Province during different periods.</p><p><b>METHODS</b>Quick surveys on the positive rate of Influenza A (H1N1) virus hemagglutination inhibition (HI) test have been conducted for 5 times successively from November 2009 to March 2010 in 14 medical and health institutions of Changsha city, whose results were then compared with those from the sampling surveys of whole Hunan province.</p><p><b>RESULTS</b>2131 subjects were involved in this study; the total population standardized rates of antibody positive investigated for 5 times were 9.32% , 14.62%, 31.08%, 28.43% and 22.80% respectively; the population of 6-17-years-old has the highest rate of antibody positive; only 9.84% of the antibody positive subjects attributed to vaccine inoculation; there was no significant difference in the standardized positive rates between the quick serological surveys and the corresponding sampling survey of Hunan province (P > 0.05).</p><p><b>CONCLUSION</b>The positive rate of A (H1N1) virus antibody reached the peak in late January 2010; quick investigations in small region could be used to evaluate the infection prevalence during pandemic of infectious diseases.</p>

Spleen-preserving distal pancreatectomy with conservation of the spleen vessels / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Distal pancreatectomy traditionally included splenectomy; the spleen, however, is an important organ in the immunologic defense of the host and is worthy of preservation. The aim of this research was to study the feasibility, safety and clinical effects of spleen and splenic vessel-preserving distal pancreatectomy.</p><p><b>METHODS</b>A retrospective review was performed for 26 patients undergoing distal pancreatectomy for benign or low grade malignant disease with splenectomy (n = 13) or splenic preservation (n = 13) at the First Hospital of Sun Yat-sen University and Guangdong General Hospital in Southern China from May 2002 to April 2009.</p><p><b>RESULTS</b>All 26 pancreatectomies with splenectomy or splenic preservation were performed successfully. There was no statistically significant difference between two groups in mean operative time ((172 ± 47) minutes vs. (157 ± 52) minutes, P > 0.05), intraoperative estimated blood loss ((183 ± 68) ml vs. (160 ± 51) ml, P > 0.05), incidence of noninfectious and infection complication and mean length of postoperative hospital stay ((10.1 ± 2.2) days vs. (12.1 ± 4.6) days, P > 0.05). The platelet counts examined one week after operation were significantly higher in the distal pancreatectomy with splenectomy group than the other group ((37.3 ± 12.8) × 10(9)/L vs. (54.7 ± 13.2) × 10(9)/L, P < 0.05).</p><p><b>CONCLUSIONS</b>Spleen-preserving distal pancreatectomy appears to be a feasible and safe procedure. In selected cases of benign or low-grade malignant disease, spleen-preserving distal pancreatectomy is recommended.</p>

Molecular characterization of highly pathogenic avian influenza A(H5N1)viruses isolated from humans in Hunan province,2006-2009 / 中华流行病学杂志

Objective To understand the possible origins,genetic re-assortment and molecular characterization of 4 highly pathogenic avian influenza A(H5N1)viruses isolated from humans in Hunan province,between 2006 and 2009,Methods H5N1 PCR test-positive specimens were inoculated in embryonated eggs while H5N1 virus was isolated and genomes sequenced.Genome homology and genetic molecular characterization were analyzed by BLAST and MEGA 4.0.Results All gene segments of the 4 viruses were avian in origin.No re-assortment was found between avian influenza A(H5N1)viruses and human seasonal influenza viruses.Virnses that isolated from domestic poultry shared high similarity with the 4 human viruses in gene homology.Data from the whole genome phylogenetic analysis showed that the 4 viruses were in clade 2.3.4,while 2 viruses belonged to genotype V,and another 2 were new genotypes.Results from molecular characterization showed that amino acid sequences of HA cleavage site of the 4 viruses were PLRERRKR/G.All 4 viruses had A160T mutation in HA,a 20 amino acid deletion in the neuraminidase(NA)stalk at position 49-68,and a 5 amino acid deletion in the non-structural protein 1(NS1).Most sites in the HA molecules showed that the viruses preferentially bound to avian influenza virus receptor.However,T192I mutation that might enhance the α2,6-linked sialic acid human influenza receptor binding had emerged in HN/1/09 and HN/2/09.D701N mutation of PB2 that increased the virulence in mice was found in HN/1/08.Analysis on drug resistance gene amino acid showed that all 4 viruses were sensitive to amantadine and oseltamivir.Conclusion Highly pathogenic avian influenza A(H5N1)viruses isolated from humans in Hunan province from 2006 to 2009 were avian in origin,and the 4 viruses belonged to different genotypes.Some mutations that related to virulence and receptor binding positions had emerged in some of the strains.

Pathogenic diagnosis of an unexplained epidemic event of infectious diarrhea / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To determine the pathogen of an unexplained epidemic event of infectious diarrhea by laboratory diagnosis of suspected cases samples.</p><p><b>METHODS</b>28 samples from 28 suspected cases (22 fecal samples, 3 vomitus samples, 3 anus swab samples) were tested for Norovirus by RT-PCR. Sequencing and phylogenetic analysis were acomplished of 5 positive samples.</p><p><b>RESULTS</b>160 of 5694 population were ill with an attack rate of 2.81%. The peak period was 7-9, March. 14 of 28 samples were tested Norovirus positive.Sequencing and phylogenetic analysis showed Norovirus type GII/4 was the causative agent and it had highest identity (97. 9%) with epidemic strain 2006b.</p><p><b>CONCLUSION</b>The epidemic event ofinfectious diarrhea were caused by GII/4 Norovirus strains.</p>

The first confirmed human case of avian influenza A (H5N1) in mainland, China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To ascertain the causation of a family cluster involving two undefined pneumonia cases, a 12-year-old girl and her brother, reported October, 2005 in Xiangtan county, Hunan province.</p><p><b>METHODS</b>Information on epidemiology and clinical manifestation of the cases was collected from interviewing the keyman and referring to related medical records. The environment exposure of the cases to their households and the timeline of the illness were reproduced, using this information. Medical check-up was undergone among the close contacts of the cases and on sick/dead poultry. Throat swab of the cases were collected and tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were then inoculated into special pathogen free (SPF) embryonated hens' eggs. Serum of the cases including acute and convalescent phases were also collected and tested by microneutralization and haemagglutination-inhibition (HI) assays to detect H5-specific antibodies.</p><p><b>RESULTS</b>Both the girl and her brother developed fever 2 and 4 days after sudden deaths of chickens being raised in the same house. Both of them had developed pneumonia and the girl died from acute respiratory distress syndrome (ARDS) complicated with multi-organ failure. The boy survived and subsequently discharged from hospital. An eighth-day serum from the girl tested H5 antibody negative, while 4-fold and greater increased in antibody titers were detected in serum from the boy using microneutralization and HI assays in sequential acute and convalescent sera. Of 192 cases, only one doctor who cared for the girl during hospitalization had upper respiratory symptoms but tested negative for H5N1 by microneutralization assay.</p><p><b>CONCLUSION</b>The boy was the first confirmed human case of avian influenza A (H5N1) in the mainland of China and his sister was diagnosed clinically. The most probable explanation of these two cases was that the transmission of H5N1 virus from infected poultry within the same household environment. No evidence of human-to-human transmission was noted in the family cluster.</p>

A study on early detection for seven infectious diseases / 中华流行病学杂志

<p><b>OBJECTIVE</b>To provide methods and alert thresholds which are scientific, sensitive, specific and practical for Early Warning System in Public Health Surveillance.</p><p><b>METHODS</b>Alert data was based on historical infectious diseases reports. Control chart was used to detect outbreaks or epidemics. An epidemic was defined by consulting Specialists. After calculating sensitivity, specificity, positive predictive value and describing receiver-operating characteristic curve (ROC), the optimal model and thresholds were chosen.</p><p><b>RESULTS</b>At 80 percentile, the sensitivities and the specificities of epidemic haemorragia fever, hepatitis A, dysentery, epidemic cerebrospinal meningitis and malaria were over 90%, and there was a high efficacy of early warning. At 90 percentile, the sensitivities and the specificities of tuberculosis and measles were over 85%, and there was a high efficacy of early warning also.</p><p><b>CONCLUSION</b>Control chart based on five years was chose as a essential method in early warning system. The alert threshold for epidemic haemorragia fever, hepatitis A, dysentery, epidemic cerebrospinal meningitis and malaria was 80 percentile. The alert threshold for tuberculosis and measles was 90 percentile.</p>