Jingjing Ren

Epidemiological features of and changes in incidence of infectious diseases in China in the first decade after the SARS outbreak: an observational trend study

Summary Background The model of infectious disease prevention and control changed significantly in China after the outbreak in 2003 of severe acute respiratory syndrome (SARS), but trends and epidemiological features of infectious diseases are rarely studied. In this study, we aimed to assess specific incidence and mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China and to investigate the overall effectiveness of current prevention and control strategies. Methods Incidence and mortality data for 45 notifiable infectious diseases were extracted from a WChinese public health science data centre from 2004 to 2013, which covers 31 provinces in mainland China. We estimated the annual percentage change in incidence of each infectious disease using joinpoint regression. Findings Between January, 2004, and December, 2013, 54 984 661 cases of 45 infectious diseases were reported (average yearly incidence 417·98 per 100 000). The infectious diseases with the highest yearly incidence were hand, foot, and mouth disease (114·48 per 100 000), hepatitis B (81·57 per 100 000), and tuberculosis (80·33 per 100 000). 132 681 deaths were reported among the 54 984 661 cases (average yearly mortality 1·01 deaths per 100 000; average case fatality 2·4 per 1000). Overall yearly incidence of infectious disease was higher among males than females and was highest among children younger than 10 years. Overall yearly mortality was higher among males than females older than 20 years and highest among individuals older than 80 years. Average yearly incidence rose from 300·54 per 100 000 in 2004 to 483·63 per 100 000 in 2013 (annual percentage change 5·9%); hydatid disease (echinococcosis), hepatitis C, and syphilis showed the fastest growth. The overall increasing trend changed after 2009, and the annual percentage change in incidence of infectious disease in 2009–13 (2·3%) was significantly lower than in 2004–08 (6·2%). Interpretation Although the overall incidence of infectious diseases was increasing from 2004, the rate levelled off after 2009. Effective prevention and control strategies are needed for diseases with the highest incidence—including hand, foot, and mouth disease, hepatitis B, and tuberculosis—and those with the fastest rates of increase (including hydatid disease, hepatitis C, and syphilis). Funding Chinese Ministry of Science and Technology, National Natural Science Foundation (China).

Factors influencing immunologic response to hepatitis B vaccine in adults

Hepatitis B was still a worldwide health problem. This study aimed to conducted a systematic review and meta-analysis to assess a more precise estimation of factors that influence the response to hepatitis B vaccine in adults. Our included studies examined seroprotection rates close to the end of vaccination schedules in healthy adult populations. This meta-analysis including 21053 adults in 37 articles showed that a significantly decreased response to hepatitis B vaccine appeared in adults (age ≥ 40) (RR:1.86, 95% CI:1.55–2.23), male adults (RR:1.40, 95% CI:1.22–1.61), BMI ≥ 25 adults (RR:1.56, 95% CI:1.12–2.17), smoker (RR:1.53, 95% CI:1.21–1.93), and adults with concomitant disease (RR:1.39, 95% CI:1.04–1.86). Meanwhile, we further found a decreased response to hepatitis B vaccine appeared in adults (age ≥ 30) (RR:1.77, 95% CI:1.48–2.10), and adults (age ≥ 60) (RR:1.30, 95% CI:1.01–1.68). However, there were no difference in response to hepatitis B vaccine both in alcoholic (RR:0.90, 95% CI:0.64–1.26) and 0-1-12 vs. 0-1-6 vaccination schedule (RR:1.39, 95% CI:0.41–4.67). Pooling of these studies recommended the sooner the better for adult hepatitis B vaccine strategy. More vaccine doses, supplemental/additional strengthening immunity should be emphasized on the susceptible population of increasing aged, male, BMI ≥ 25, smoking and concomitant disease. The conventional 0-1-6 vaccination schedule could be still worth to be recommended.

Distinguishing Nontuberculous Mycobacteria from Multidrug-Resistant Mycobacterium tuberculosis, China

To the Editor: Mycobacteria are commonly characterized by positive acid-fast staining. Most mycobacterial species belong to the nontuberculous mycobacteria (NTM), excluding species in the Mycobacterium tuberculosis complex and M. leprae. Both M. tuberculosis and NTM can induce pulmonary infection with similar symptoms and pulmonary radiographic findings (1). These similarities have led to difficulty in distinguishing these infections clinically. As in many developing countries, the acid-fast stain is the only bacteriologic basis for diagnosing tuberculosis (TB) in primary health care institutions in China, where facilities are limited for M. tuberculosis culture, strain identification, and drug resistance detection. Thus, NTM is easily misdiagnosed as M. tuberculosis, and multidrug-resistant (MDR) TB is unable to be accurately identified. Patients with misdiagnosed TB usually are treated with the standard anti-TB regimens recommended by the Chinese government (i.e., 2HRZE/4HR [2 months of isoniazid (INH), rifampin (RIF), pyrazinmid, and ethambutol, followed by 4 months of INH and RIF 1 time daily] and 2H3R3Z3E3/4H3R3 [2 months of INH, RIF, pyrazinamide, and ethambutol followed by 4 months of INH and RIF 3 times weekly]) (2), which often results in treatment failures. Misdiagnosis is a key hurdle for effective prevention and treatment of TB (3–5). To evaluate the effect of misdiagnosis on TB prevention, we determined the proportion of patients with MDR TB and NTM infection in primary health care institutions in Zhejiang Province, China. Our findings would be useful for improving TB prevention and treatment. During 2011–2012, sputum samples from 13,882 patients suspected of having TB in 8 counties in Zhejiang Province were used to culture mycobacteria. Each sample was seeded onto 2 pieces of Lowenstein-Jensen medium. A total of 1,410 samples grew mycobacteria confirmed as acid-fast bacilli by using Ziehl-Neelsen staining. The 1,410 samples were further identified by using the Mycobacteria Identification Array Kit (CapitalBio, Beijing, China). The kit contains 17 types of bacilli-specific 16S rRNA probes (i.e., M. tuberculosis complex, M. avium, M. intracellulare, M. gilvum, M. xenopi, M. smegmatis, M. aurum, M. terrae, M. gordonae, M. chelonae/abscessus, M. phlei, M. scrofulaceum, M. fortuitum, M. szulgai, M. ulcerans, M. marinum, and M. kansasii). With this method, M. tuberculosis and NTM can be distinguished, and the species of NTM can be identified (6–8). Of 1,410 positive strains, we identified 1,332 (94.5%) as M. tuberculosis and 78 (5.5%) as NTM. NTM strains were further identified as follows: M. intracellulare, 39 isolates; M. chelonae/abscessus, 12 isolates, M. kansasii, 13 isolates; M. avium, 3 isolates; M. fortuitum, 4 isolates; and M. scrofulaceum and M. szulgai, 1 isolate each. For 5 isolates, strain could not be classified. We detected drug resistance of 1,332 M. tuberculosis strains using a Tuberculosis Drug Resistance Detection Array Kit (CapitalBio) (9). The mutant points for RIF resistance were identified as follows: rpoB/C531G, C531T, CG531AC, A526C, A526G, A526T, C526A, C526G, C526T, T533C, A516G, A516T, G516T, T511C, T511G, C513A, A513T, and C522T (Table). Moreover, the kit contained 5 mutant points for INH resistance, including katG (G315A, G315C, G315T, and C315) and inhA (C-15T) (Table). Of 1,332 M. tuberculosis strains, we identified 1,115 (83.7%) RIF/INH-sensitive strains, 88 (6.6%) MDR TB strains, 83 (6.2%) INH-resistant strains, and 47 (3.5%) RIF-resistant strains. Of the 1,410 positive strains, 88 (6.2%) were MDR M. tuberculosis strains. Table Gene mutations of 214 drug-resistant tubercle bacilli, Zhejiang Province, China, 2011–2012 The epidemiology of TB in Zhejiang Province reflects the situation in China and some developing countries (10). The clinical diagnosis and treatment of >80% TB cases in China is performed mainly by primary health care institutions. However, almost 80% of these medical institutions do not have the capability to culture M. tuberculosis, detect drug resistance, and identify strains (7). Of 1,410 strains obtained from the patients in 8 counties of Zhejiang Province, 218 (15.5%) were MDR TB, INH resistant, and RIF resistant. These affected patients could not be effectively treated with the national standard regimens. Specifically, 88 patients with MDR TB would be at risk for extensively drug-resistant TB, and 83 patients with INH-resistant TB and 47 with RIF-resistant TB would be at risk for MDR TB. In addition, we identified 78 (5.5%) NTM strains. With the acid-fast stain, these illnesses would be misidentified as TB and, in most instances, also would be reported as treatment failures. Clearly, accurate diagnosis provided by the technologies used in this study for distinguishing NTM and M. tuberculosis, Mycobacterium strain identification, and drug-resistance detection would increase the cure rate and effectively prevent TB epidemics. For INH resistance, katG315 was a main mutant point of the M. tuberculosis strain; 140 (81.4%) of the 172 INH-resistant mutations were related to katG315. For RIF resistance, rpoB531 was a main mutant point; 84 (60.0%) of 140 RIF-resistant mutations were associated with rpoB531. Therefore, in future studies, more attention should be paid to the molecular epidemiology of katG315 and rpoB531. In conclusion, using the techniques for M. tuberculosis culture, Mycobacterium strain identification, and drug-resistance detection is necessary. It should be urgently pursued for accurate TB diagnosis in primary health care institutions in China to improve the prevention, treatment, and control of TB.

The effects of booster vaccination of hepatitis B Vaccine on anti-HBV surface antigen negative children 11-15 years after primary vaccination

The twin aims of this study were to investigate the changes in anti-HBs IgG levels after booster vaccinations and to compare the effects of different vaccine doses in children aged 11-15 years who were both negative for HBsAg and had an Anti-HBs

Transmission of Hepatitis B and C Virus Infection Through Body Piercing: A Systematic Review and Meta-Analysis.

AbstractHepatitis B and hepatitis C are 2 types of potentially life-threatening liver diseases with high infection rate. Body piercing represents a progressively popular sociocultural phenomenon which is also a potential exposure approach for hepatitis B virus (HBV) and hepatitis C virus (HCV). Conclusions from those researches with statistically risk assessment of body piercing on HBV and HCV transmission are contradictory.Systematically analyze the association between body piercing and the risk of transmitting hepatitis B virus and hepatitis C virus for general population. Make evidence-based recommendations to the current practice and wake up public awareness of this health-threatening behavior.Comprehensive and high sensitivity search strategies were performed to exhaustively search related studies before 15 January 2015 (MEDLINE, EMBASE, WANFANG, CNKI datasets for published literatures, and Google and Google scholars for related grey articles). Two authors identified relevant studies for the review, abstracted data, and assessed literature quality independently and critically according to the selection criteria and quality assessment standard. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to estimate risk of HBV and HCV infection in relation to body piercing status. Subgroup analysis and sensitivity analysis were conducted to examine the source of heterogeneity and test the robust of the results.A total of 40 studies were included in this systematic review (10 for Hep-B, 26 for Hep-C, 4 for both Hep-B and Hep-C), the pooled OR (95% CI) for the association between body piercing and transmission of HBV/HCV is 1.80 (1.18, 2.75) and 1.83 (1.27, 2.64), respectively. Subgroup analysis suggested that highest risk of body piercing related to hepatitis C infection was for former soccer and veterans with OR of 4.63 (2.65, 8.10), while strongest association between body piercing and hepatitis B was for samples derived from students/community with OR of 2.40 (1.44, 4.02).The current systematic review and meta-analysis suggests that body piercing is significantly associated with the transmission of HBV as well as HCV, having body piercing probably can increase the risk of getting infected. Evidence from this study strongly recommends that comprehensive and effective programs should be established to provide safer piercing practice.

Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China

The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95% CI: 0.77–0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV, and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r = −0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination.

Comparison of the effect of two different doses of recombinant hepatitis B vaccine on immunogenicity in healthy adults

The aim of this study was to evaluate the one-month immune response to 2 different doses (10 and 20 μg) of recombinant hepatitis B vaccine in adults aged 20–46 y. Subjects who were negative for hepatitis B surface antigen (HBsAg), hepatitis B antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) were recruited. The participants were divided into 2 groups: group I received 3 doses of 10 μg hepatitis B vaccine at 0, 1 and 3 months, and group II received 3 doses of 20 μg at the same time points. The anti-HBs levels were measured one month after the third vaccination. Among 739 subjects, 62 (9.70%) were positive for HBsAg, and 317 subjects were eligible. The anti-HBs seroprotection rates (anti-HBs ≥10 mIU/mL was considered to indicate seroprotection) after the third vaccination were 88.05% and 94.06% in group I and group II respectively, and the geometric mean titers were 91.69 and 290.23 mIU/mL respectively. The difference in the seroprotection rate was not significant (χ2 = 2.566, P > 0.05), but the GMT after the third dose was significantly lower for group I than for group II (F = 20.587, P < 0.05). Better responses were observed in young adults, especially in group I. In group I, the seroprotection rate and GMT were significantly higher in the 20–35 y group than in the 36–46 y group (P < 0.05); there was no significant difference compared to group II (P > 0.05). The hepatitis B vaccine has good immunological effect; the 20 μg dose can be used in adults aged 20–46 y and the 10 μg dose can be used in subjects aged 20–35 years, and it should be tested on a larger number of subjects before recommending it for adult routine vaccination.

Serolological Profile Among HBsAg-Positive Infections in Southeast China: A Community-Based Study

Background Hepatitis B virus (HBV) infection has remained a significant public health problem. Generating a large-scale, community-based profile of HBV infection in China is essential to prevention of the disease. Objectives The current study was designed to investigate HBV-infected individuals at the community level and determine the age distribution, hepatitis B e antigen (HBeAg) positivity and its related risk factors, relationship among serological markers. Patients and Methods A cross-sectional, community-based survey was carried out without age restriction, in 12 communities of two counties. The study population was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 8439 HB surface antigen (HBsAg)-positive individuals. Results The constituent ratio of individuals with HBsAg-positive infections was lowest among persons aged < 20 years (0.4%) and the highest among persons aged 40-49 years (33.2%). The HBeAg-positive rate among infected individuals was 18.5%, and the constituent ratio decreased with increasing of age. The HBeAg-positive rate in males (21.9%) was significantly higher than in females (14.7%), and was higher among coastland inhabitants (22.9%) than among plains inhabitants (12.9%). Among the 1561 HBeAg-positive individuals, 91.0% were HBV DNA-positive. However, of the 6878 HBeAg-negative individuals, only 45.4% were HBV DNA-positive, and the HBeAg-positive rate was significantly different at different levels of HBV DNA expression. The proportion of detectable HBV DNA levels was significantly higher in individuals with elevated ALT, compared to those with normal ALT, regardless of HBeAg-positivity. Conclusions The HBV prevalence remained high in the > 20 age group. The positivity of HBeAg was related to age, region, and sex. Testing HBeAg and serum ALT levels were effective ways to assess HBV infectiousness in community-level hospitals in China.

Immunological effects of a 10-μg dose of domestic hepatitis B vaccine in adults

ObjectiveTo evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination.MethodsAdults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6 months. Anti-HBs levels were assessed one month after the third and final vaccination.ResultsA total of 1 872 adults were immunized and the average positive rate was 89.5%. Four types of hepatitis B vaccine were used, including three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China Pharmaceutical) and one from a UK company (GlaxoSmithKline). Their seroconversion rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a significant difference between the anti-HBs positive conversion rates of the four types (P<0.005) but the seroconversion rates among the different vaccines were not significantly different (χ2=2.123, P=0.145). The average anti-HBs geometric mean titers (GMTs) of non-immune adults immunized with each of the four vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were no statistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t=−1.575, P=0.116).ConclusionsDomestic recombinant hepatitis B vaccines can achieve immunization effects comparable to those of a foreign vaccine.

The Use of Mobile Phone and Medical Apps among General Practitioners in Hangzhou City, Eastern China

Background Mobile phones and mobile phone apps have expanded new forms of health professionals’ work. There are many studies on the use of mobile phone apps for different specialists. However, there are no studies on the current use of mobile phone apps among general practitioners (GPs). Objective The objective of the study was to investigate the extent to which GPs own smartphones with apps and use them to aid their clinical activities. Methods A questionnaire survey of GPs was undertaken in Hangzhou, Eastern China. Data probing GPs’ current use of medical apps in their clinical activities and factors influencing app use were collected and analyzed Results 125 GPs participated in the survey. 90.4% of GPs owned a mobile phone, with 48.7% owning an iPhone and 47.8% owning an Android phone. Most mobile phone owners had 1-3 medical-related apps, with very few owning more than 4. There was no difference in number of apps between iPhone and Android owners (χ2=1.388, P=0.846). 36% of GPs reported using medical-related apps on a daily basis. The majority of doctors reported using apps to aid clinical activities less than 30 minutes per day. Conclusions A high level of mobile phone ownership and usage among GPs was found in this study, but few people chose medical-related apps to support their clinical practice.