[Epidemiological characteristics of pulmonary tuberculosis in Guangdong province from 2016 to 2020].

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (TB) in Guangdong province from 2016 to 2020 and provide evidence for the prevention and control of pulmonary TB. Methods: Descriptive epidemiological methods were used to analyze the incidence data of pulmonary TB reported in Guangdong from 2016 to 2020. Dynamic geometric series averaging and circular distribution methods were used to reveal the epidemic pattern. Results: A total of 356 748 pulmonary TB cases were reported in Guangdong from 2016 to 2020. The reported incidence of pulmonary TB decreased from 71.82/100 000 to 50.40/100 000 (trend χ2=6 905.57,P<0.001) , with an annual decline rate of 8.47%. Results from the circular distribution methods showed that the incidence peak would occur on May 4th-5th (Z=1 176.96,P<0.05), and the incidence was relatively higher in May compared with other months. The area distribution of the pulmonary TB epidemic was uneven, and the reported average annual incidence was in the order of the eastern area (72.15/100 000), the northern area (68.14/100 000), the western area (65.31/100 000) and the Pearl River Delta area (60.05/100 000). Results of dynamic geometric series averaging analysis showed a declining trend in the reported incidence of pulmonary TB in all areas, except Dongguan, with the average growth rate less than 0.00. The decline rate in the eastern area (-10.90%) and northern area (-10.63%) was higher than the provincial average (-8.47%). The male to female ratio of the cases was 2.63∶1 (258 562∶98 186). The reported average annual pulmonary TB incidence in men (88.37/100 000) was higher than that in women (36.86/100 000), the difference was significant (χ2=75.19, P<0.001). The reported incidence of pulmonary TB generally increased with age (trendχ2=123 849.44, P<0.001), and reached peak in age group ≥65 years (164.54/100 000). Dynamic geometric series averaging analysis showed an increasing trend of the reported pulmonary TB incidence in age groups 5-14 years and 15-24 years, with the average growth rate of 0.05% and 3.60%. Conclusions: The reported annual incidence of pulmonary TB showed a declining trend year by year in Guangdong from 2016 to 2020. However, an increasing incidence was reported in children and adolescents. Active case finding should be strengthened in the elderly and other key populations. With comprehensive TB prevention and control measures, it is still necessary to pay attention to the prevention and control of pulmonary TB in men, low-income groups and less developed areas in Guangdong and strengthen the comprehensive prevention and control in winter and spring.

[Review on the etiology and complications of hand, foot and mouth disease, using data from the national sentinel surveillance program, in China, 2015-2016].

Objective: To understand the characteristics relating to the etiology and complications of hand, foot and mouth disease (HFMD) based on data from the pilot National Sentinel Surveillance (NSS) program so as to explore the feasibility, advantages and disadvantages of the NSS. Methods: Data were extracted from the NSS system, conducted in 11 provinces of China from November 2015 to October 2016. Characteristics regarding the etiology, complications of HFMD and factors related to the positive rates of HFMD specimens were analyzed under the logistic regression method by SPSS 20.0 software. Results: A total of 4 783 specimens were collected, including 3 390 from mild, 1 390 from severe and 3 from death cases. The overall positive rate was 81.43% (3 895/4 783). Other enteroviruses (non EV71/Cox A16 enteroviruses) appeared the major serotype (52.68%, 1 482/2 813) for mild infection of the disease while EV71 was for the severe cases (65.31%, 706/1 081). The serotype spectrum revealed by the pilot NSS was almost identical with the existing surveillance system. Other enteroviruses tended to infect younger children (χ(2)=130.17, P<0.001) than EV71 and Cox A16, in China. The multivariate logistic regression results showed that higher positive rate was associated with specimens which were collected from males, at children' hospitals, in peak seasons, timely and in stools. The positive rates presented downwarding trends with the extension of the onset-sampling interval (χ(2)=14.47, P<0.001 in stool specimen; χ(2)=31.99, P<0.001 in throat swab; χ(2)=24.26, P<0.001 in anal swab). Aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis appeared the top three complications of both EV71-associated and other enteroviruses-associated severe HFMD cases. Conclusions: Factors as gender, season/place/timeliness of specimen collection, and types of hospital all appeared independently influenced the positive rates. NSS seemed feasible to be used as an alternative or supplement tool to the existing surveillance program in China.

[Hospitalization burden of hand, foot and mouth disease in Anhua county of Hunan province, 2013-2016].

Objective: To estimate the serotype and age-specific hospitalization burden associated with hand, foot and mouth disease (HFMD) in Anhua county of Hunan province, between October 2013 and September 2016. Methods: We collected hospitalization records of HFMD patients from 6 virological surveillance hospitals, and reimbursement records through new rural cooperative medical system from 23 township health centers to estimate the age-specific hospitalization burden of HFMD in Anhua. Combined with the results of virological surveillance, the serotype-specific hospitalization burden of HFMD in Anhua, was estimated. Results: During the three years, it was estimated that 3 541 clinical diagnosed HFMD cases, including 3 146 laboratory-confirmed HFMD cases, were hospitalized in Anhua, but only one was diaguosed as being severe. The estimated average hospitalization rate was 723/100 000(95%CI: 699/100 000-747/100 000) for clinical diagnosed HFMD and 642/100 000 (95%CI: 620/100 000-665/100 000) for laboratory-confirmed HFMD between October 2013 and September 2016. The cases caused by Cox A16 (208/100 000) and Cox A6 (202/100 000) had higher hospitalization rates compared with the cases caused by EV71 (130/100 000), Cox A10 (38/100 000) and other enterovirus (64/100 000), and the difference was statistically significant (P<0.001). HFMD-associated hospitalization rates peaked in children aged 1 year (3 845/100 000), and then decreased with age. Compared with the hospitalized HFMD caused by EV71 and Cox A16, Cox A6-associated hospitalizations mainly occurred in younger age groups (P<0.001). Conclusion: Our study revealed a substantial hospitalization burden associated with mild HFMD caused by EV71, Cox A16, Cox A6 and Cox A10, especially in young children, in Anhua.

[Epidemiological characteristics and molecular typing of typhoid and paratyphoid in China, 2009-2013].

Objective: To understand the epidemiological and molecular characteristics of typhoid and paratyphoid in China from 2009 to 2013, and provide evidence for the prevention and control of typhoid and paratyphoid, the development and improvement of surveillance strategies. Methods: Epidemiological analysis was conducted on the incidence data of typhoid and paratyphoid, and related public health emergencies in China during 2009-2013. Pathogen isolation and culture, serologic test were conducted for the typhoid and paratyphoid cases from 13 national surveillance sites. The isolates were subjected to antimicrobial susceptibility testing. Pulsed-field gel electrophoresis (PFGE) was performed for the molecular typing of these isolates. Results: The average incidence of typhoid and paratyphoid in China during this period was 1.03/100 000. The reported case number and incidence decreased with year. The provinces reporting high case numbers were Yunnan, Guizhou, Guangxi, Hunan, Zhejiang, Guangdong and Xinjiang. The incidence of age group 0-4 years was highest. The proportion of farmers and children outside child care settings showed an increasing tendency over time. The annual incidence peak was during July-August. Twenty five outbreaks occurred during 2009-2013. The results of pathogen isolation and culture showed that the positive rate was 3.00% (940/31 322), among the positive isolates, the proportion of Salmonella paratyphi A accounted for higher proportion (68.19%, 641/940) compared with Salmonella typhi (31.60%, 297/940). The drug resistances of Salmonella typhi and Salmonella paratyphi varied, but their resistances to nalidixic acid were highest (50.22% and 85.33%) respectively. A certain amount of Salmonella typhi isolates showed the resistance to the 3rd generation cephalosporins. PFGE analysis showed divergent patterns of Salmonella typhi compared with limited patterns of Salmonella paratyphi A. Conclusion: The epidemic level of typhoid and paratyphoid in China was relatively low, but the outbreak occurred occasionally. It is necessary to enhance the laboratory-based surveillance, particularly the capability of etiological diagnosis, outbreak investigation, response and antibiotic resistance monitoring, and conduct risk factor investigation in provinces with high incidences in recent years.

[Surveillance data on typhoid fever and paratyphoid fever in 2015, China].

Objective: Through analyzing the surveillance data on typhoid fever and paratyphoid fever in 2015 to understand the related epidemiological features and most possible clustering areas of high incidence. Methods: Individual data was collected from the passive surveillance program and analyzed by descriptive statistic method. Characteristics on seasonal, regional and distribution of the diseases were described. Spatial-temporal clustering characteristics were estimated, under the retrospective space-time method. Results: A total of 8 850 typhoid fever cases were reported from the surveillance system, with incidence rate as 0.65/100 000. The number of paratyphoid fever cases was 2 794, with incidence rate as 0.21/100 000. Both cases of typhoid fever and paratyphoid fever occurred all year round, with high epidemic season from May to October. Most cases involved farmers (39.68%), children (15.89%) and students (12.01%). Children under 5 years showed the highest incidence rate. Retrospective space-time analysis for provinces with high incidence rates would include Yunnan, Guangxi, Guizhou, Hunan and Guangdong, indicating the first and second class clusters were mainly distributed near the bordering adjacent districts and counties among the provinces. Conclusion: In 2015, the prevalence rates of typhoid fever and paratyphoid fever were low, however with regional high prevalence areas. Cross regional transmission existed among provinces with high incidence rates which might be responsible for the clusters to appear in these areas.

[Severe cases with hand, foot and mouth disease: data based on national pilot hand, foot and mouth disease surveillance system].

Objective: To investigate the clinical severity, etiological classification and risk factors of severe cases with hand, foot and mouth disease (HFMD). Methods: A total of 1 489 records on severe and fatal HFMD cases reported to the national pilot surveillance system of HFMD were used to analyze the demographic, medical treatment, etiological classification of the cases. Treatment outcome related risk factors were also studied with multi-variable stepwise logistic regression method. Results: Seven out of the 1 489 severe HFMD cases died of this disease. A total of 960 (72.9%) were under three years old and 62.9% were male and most of the cases (937, 62.9%) resided in rural areas. Among all the cases, 494 (33.2%) went to seek the first medical assistance at the institutions of village or township level. Durations between disease onset and first medical attendance, being diagnosed as the disease or diagnosed as severe cases were 0(0-1) d, 1 (0-2) d and 2 (1-4) d, respectively. In total, 773 (51.9%) of the severe HFMD cases were diagnosed as with aseptic meningitis, 260 (17.5%) with brainstem encephalitis, 377 (25.3%) with non-brainstem encephalitis, 6 (0.4%) with encephalomyelitis, 1 (0.1%) with acute flaccid paralysis, 4 (0.3%) with pulmonary hemorrhage/pulmonary edema and 68 (4.6%) with cardiopulmonary failure. Of the etiologically diagnosed 1 217 severe and fatal HFMD cases, 642 (52.8%) were with EV71, other enterovirus 261 (21.5%), Cox A16 36 (3.0%), 1 (0.1%) with both EV71 and Cox A16. However, 277 (22.8%) showed negative on any pathogenic virus. Complication (Z=3.15, P=0.002) and duration between onset and diagnosed as severe cases (Z=3.95, P<0.001) were shown as key factors related to treatment outcomes. Conclusions: Most severe HFMD cases appeared in boys, especially living in the rural areas. Frequently seen complications would include aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis. EV71 was the dominant etiology for severe and fatal cases. Early diagnosis and complication control were crucial, related to the treatment outcome of HFMD.

[Hand, foot and mouth disease in Hubei province, 2009-2015: an epidemiological and etiological study].

Objective: To clarify the age patterns and types of differences so as to provide reference on prevention and interventions of hand, foot and mouth disease (HFMD) cases, in Hubei province. Methods: We collected the HFMD case information of Hubei province from the Chinese National Notifiable Infectious Disease Reporting System in 2009-2015 while the information on pathogens from the laboratory monitoring system of Center for Disease Control and Prevention at all levels in Hubei province. All the data were stratified by age, disease severity, laboratory confirmation status, and serotypes of enterovirus. Results: There were 495 783 reported HFMD cases from 2009 to 2015, in Hubei province, of which 1 045 were severe with 99 fatal. The annual notification rate was 1 231.0/10(6). HFMD cases were concentrated mainly in 0.5-5 year olds, with highest severity and mortality seen in 6-11 month-olds. The predominated pathogen in mild laboratory-confirmed cases each year, in order during 2009-2015 as: EV71, Cox A16, Cox A16, Cox A16, EV71, Cox A16 and other EV. HFMD showed semiannual peaks in April-June, November-December, and with more cases in the even years than in the odd years. Conclusions: Children aged 0.5 to 5 years with 6 to 11 month-olds in particular, were the focused groups of attention in Hubei province. Our findings provided evidence for the improvement on monitoring program. Targeted intervention approaches should be strengthened to reduce the mortality and morbidity of HFMD in the province.

[Health related quality of life on severe hand, foot and mouth disease patients].

Objective: To evaluate the health related quality of life (HRQoL) for severe hand, foot and mouth disease (HFMD) patients with different complications. Methods: A national telephone interview under the EQ-5D proxy2 questionnaire (EQ-SD and EQ-VAS), was conducted to obtain the HRQoL of lab-confirmed severe HFMD patients, aged between six months and five-year-olds from the national communicable disease surveillance system from January 1, 2012 to December 31, 2013. Results: A total of 685 severe HFMD cases were included in the study. A total of 456 (66.6%) of them were males with 75.8% of them younger than three years old. A total of 337 (49.2%) and 407 (59.4%) of the participants reported that they had problems in mobility or daily activities. A total of 569 (83.1%) and 616 (89.9%) of the cases reported having problems in pain/discomfort or anxiety/depression. The average EQ-5D and EQ-VAS scores were 0.58±0.23 and 53.6±25.7, both were positively associated with the duration of illness. Mean quality adjusted life years loss during the HFMD episode for the severe patients was (15.45±13.75) years/1 000 persons. The QALY losses for severe patients with each of below complication were: respiratory diseases (11.17±8.83) years/1 000 persons, aseptic meningitis (13.56±11.99) years/1 000 persons, encephalitis/brainstem encephalitis/acute flaccid paralysis (AFP) (15.31±12.63) years/1 000 persons, Myocarditis (17.28±18.16) years/1 000 persons, pulmonary hemorrhage/pulmonary edema (17.34±14.98) years/1 000 persons, cardiopulmonary failure (25.47±20.53) years/1 000 persons. Among patients with lab confirmed Entero virus A71 (EV71) (16.51±14.48) years/1 000 persons, the QALY loss was seen higher than Coxsackie virus A16 (Cox A16) (13.02±11.45) years/1 000 persons and other Enter virus (14.74±14.22) years/1 000 persons (Z=11.83, P=0.003). Conclusion: The HRQoL loss for severe HFMD patients substantially increased under complications exacerbation and related to the duration of illness.

[Direct medical costs and influencing factors in severe hand, foot and mouth disease in children aged between six months and five years old].

Objective: To estimate the direct medical cost of severe hand, foot and mouth disease (HFMD) in patients aged less than five years. Methods: A stratified sampling method was used to collect data on severe HFMD cases reported in the National HFMD surveillance database between Jan 1, 2012, and Dec 31, 2013. The sampling was referenced with the national aetiologic distribution of Enterovirus A71 (EV-A71), Coxsackievirus A16 (CV-A16) and other Enteroviruses (OEV) for severe HFMD cases and the included cases were distributed among seven geographic regions (Northeast, North China, Northwest, Central China, Southwest, East China and South China). A nationwide telephone interview using a structured questionnaire was conducted to obtain the direct medical cost and any complications that occurred in patients during the outbreak of laboratory-confirmed HFMD. After excluding the cases who could not recall their medical expenses or complications, a total of 685 cases were included in the analysis. Kruskal-Wallis H test was used to analyze the differences among patients who reported different complications. Multiple linear regression with bootstrap analysis of 500 replicates was used to explore the factors that influenced the direct medical costs. Results: Of 685 patients analyzed, 456 (66.6%) were male and 229 (33.4%) were female. The direct medical costs P50 (P25, P75) were 14 250 (10 301, 20 600) Yuan. In total, 127 (18.5%) patients were diagnosed with severe HFMD patients with respiratory disease, 38 (5.5%) patients were diagnosed with aseptic meningitis, and 378 (55.2%) with encephalitis/brainstem encephalitis/acute flaccid paralysis. Furthermore, 53 (18.5%) patients were diagnosed with myocarditis, 39 (5.7%) with pulmonary hemorrhage/pulmonary edema and 50 (7.3%) with cardiopulmonary failure. The median (interquartile range) direct medical costs were 12 360 (7 313, 16 480) Yuan for severe HFMD patients with respiratory disease, 13 803 (9 064, 19 930) Yuan for aseptic meningitis, 14 438 (11 000, 20 015) Yuan for encephalitis/brainstem encephalitis/acute flaccid paralysis, 14 800 (8 500, 21 218) Yuan for myocarditis, 20 600 (12 500, 31 130) Yuan for pulmonary hemorrhage/pulmonary edema, and 20 043 (12 772, 28 840) Yuan for cardiopulmonary failure (H=17.70, P<0.001). The results of multiple linear regression with bootstrap analysis revealed that the direct medical cost for severe HFMD patients from Central China was 7 881 (95% CI: 3 814-11 949) Yuan higher than that of North China; severe HFMD patients diagnosed with OEV had direct medical costs of 1 987 (95%CI: 206-3 769) Yuan less those associated with EV-A71; severe HFMD patients whose duration of illness was ≥21 d had 20 480 (95% CI: 10 985- 29 974) Yuan higher direct medical costs those whose illness lasted ≤5 d; the direct medical costs for severe HFMD patients with pulmonary hemorrhage/pulmonary edema and cardiopulmonary failure were 7 874 (95%CI: 3 723-12 026) and 9 855 (95% CI: 328- 19 382) Yuan higher, respectively, than that associated with respiratory disease. Conclusion: The direct medical costs associated with severe HFMD were found to be substantial. The total cost was affected by the duration of the illness and the severity of any complications.

[Influence of sociocultural factors on HIV transmission among men who have sex with men: a qualitative study].

Objective: To understand how social and cultural factors influence sexual perceptions, sexual practices, and HIV transmission among men who have sex with men at selected sites in China. Methods: Qualitative methodology was used and face to face, semi-structured, in-depth interviews conducted from April 2013 to October 2015 in Sichuan, Jiangxi, Henan, Heilongjiang provinces and Chongqing municipality of China. Results: A total of 184 men who have sex with men participated in the interviews. Forty-eight originated from Henan Province, and 12, 50, 47, and 27 from Jiangxi, Heilongjiang, Sichuan provinces and Chongqing municipality, respectively. A total of 122 participants(66.3%)were under 30 years of age, 111 were college graduates(61.3%), 140 were unmarried(76.5%), and 74 were HIV positive(40.2%). Among interviewees, 6%(11 MSM)were employed at nongovernmental organizations. The main findings revealed that: Owing to sociocultural influences and social norms, most homosexual men concealed their sexual orientation and married females so as to fulfill their family obligation; this may encourage HIV transmission from a high-risk population to the general population; the main features of male homosexual behaviors, as well as those of the associated community and subculture, included hedonism, less concern about health, drug abuse, encouraging of high risk behaviors among men who have sex with men, and negative attitudes regarding HIV prevention; subgroups among MSM were found to have differential HIV transmission risk behaviors, with young men more vulnerable to infection with HIV. Conclusion: Sociocultural factors, including external socioenvironmental circumstances and internal MSM community subcultures, have adverse impacts on HIV transmission among men who have sex with men. Because there were varied behavior modes and HIV transmission risks among MSM subgroups, further study focusing on MSM subgroups is imperative, to provide a basis for more targeted and effective prevention strategies.

An hepatitis B virus surface antigen specific single chain of variable fragment derived from a natural immune antigen binding fragment phage display library is specifically internalized by HepG2.2.15 cells.

Hepatitis B virus surface antigen (HBsAg), a specific antigen on the membrane of hepatitis B virus (HBV)-infected cells, provides a perfect target for therapeutic drugs. In order to mediate successful targeted delivery of these therapies, it is essential to have antibodies that recognize HBsAg with high specificity and affinity. In this report, we constructed a natural immune antigen binding fragments (Fab) antibody phage display library against HBsAg and after three rounds of panning, five Fab fragments with significant HBsAg binding ability were selected and analysed. DNA sequencing revealed that all the light chains had the same sequence, while all the Fd genes exhibited different sequences. For further application, all of the Fab antibodies were reconstructed into single chain antibodies (scFvs) and expressed in Escherichia coli BL21 cells. Indirect enzyme-linked immunosorbent assay analysis demonstrated that all five scFvs maintained a high affinity for HBsAg and could bind HBsAg on the membrane of HBV-infected cells. Indirect fluorescent staining analysis revealed that one of the scFvs (scFv15) could be internalized into HBsAg-positive HepG2.2.15 cells through clathrin-mediated endocytosis pathway. The internalizing scFv15 antibody would have great potential for the targeted delivery of therapeutics to HBV-infected cells.