Background: Given the significant impact of population immunity on the measles epidemic, understanding immunity differences among populations with varying immunity backgrounds is necessary for identifying immunity gaps and informing vaccination policies. In this study, we aimed to determine the distinct dynamics of vaccine-induced and naturally acquired antibodies, with specific focus on difference in vaccine-induced antibody responses across different birth cohorts. Methods: Based on two cohorts and one cross-sectional study conducted in Anhua County, Hunan Province, China, serum samples from children who followed China's routine measles vaccination schedule (i.e., two-dose schedule at 8/18 months) and adults who acquired immunity through natural infection were tested for measles IgG antibodies using an enzyme-linked immunosorbent assay. The generalized additive mixed model and a mechanistic model were employed to describe antibody dynamics following vaccination and infections. Wavelet analysis was used to investigate the temporal relationship between the measles epidemic and long-term antibody levels after natural infection. Results: A total of 408 children (0-12 years) and 222 adults (54-84 years) were included in the present study. Vaccine-induced antibody levels following 8 m/18 m vaccination were estimated to fall below the protective threshold of 200 mIU/mL by age of 15.8, whereas antibody levels following infections remained high. The decay rate of vaccine-induced antibodies was estimated at 3.0 × 10-3 log-log mIU/mL per year, whereas naturally acquired measles antibodies persisted lifelong with a significantly lower decay rate of 2.30 × 10-5 log-log mIU/mL per year. Moreover, vaccine-induced antibody levels in children born after 2010-a period of low measles incidence-declined more rapidly (duration of protective immunity: 12.5 years), compared to those born before 2010. Discussion: Our findings revealed immunity heterogeneity among individuals with difference measles immunity backgrounds. In particular, the birth-cohort specific differences in vaccine-induced immunity highlighted the key role of young generations born in settings with low measles incidence in contributing to population immunity gaps. This underlines that greater attention should be given to this group in future catch-up vaccination efforts.

BACKGROUND:The 2009 pandemic H1N1 influenza A virus (A(H1N1)pdm09 virus) evolves rapidly and has continued to cause severe infections in children since its emergence in 2009. We aimed to characterise the kinetics of maternally and naturally acquired antibodies against historical A(H1N1)pdm09 strains and to assess the extent to which the response to heterologous strains following infection or vaccination affects observed A(H1N1)pdm09 strain-specific antibody titres in a Chinese paediatric population. METHODS:In this retrospective study, we used residual serum samples from 528 mother-neonate pairs from a non-interventional, longitudinal cohort study in southern China conducted from Sept 20, 2013, to Aug 24, 2018, from six local hospitals in Anhua County, Hunan Province, China. Mother-neonate pairs were eligible for inclusion if the neonates were born after Sept 20, 2013, and their mothers had resided in the study sites for at least 3 months. We tested samples with a haemagglutination inhibition (HAI) assay to measure antibody levels against three historical A(H1N1)pdm09 strains that were antigenically similar to the strains that circulated during the 2009 pandemic (A/Hunan-Kaifu/SWL4204/2009 [SWL4204/09 strain], A/Hunan-Daxiang/SWL1277/2016 [SWL1277/16 strain], and A/Hunan-Yanfeng/SWL185/2018 [SWL185/18 strain]). We also determined the seroprevalence, geometric mean titres (GMTs), transfer ratio of maternal antibodies, and the dynamics of maternally and naturally acquired antibodies in children, from birth to 3 years of age. FINDINGS:1066 mother-neonate pairs were enrolled in the original cohort between Sept 20, 2013, and Oct 14, 2015. Of these, 528 pairs (523 mothers, 528 neonates) were selected for the present study. The median age of the mothers was 25 years (IQR 23 to 29). 291 (55%) of 528 children were boys and 237 (45%) were girls, and most children (452 [86%]) were breastfed before the age of 6 months. The GMTs and the seroprevalence for the SWL4204/09 strain were higher than those for the SWL1277/16 and SWL185/18 strains among mothers (GMTs: 10·4 [95% CI 9·8 to 11·1] vs 9·3 [8·7 to 9·8] vs 8·0 [7·5 to 8·4], p<0·0001; seroprevalence: 11·1% [95% CI 8·5 to 14·1] vs 6·9% [4·9 to 9·4] vs 4·6% [3·0 to 6·8], p=0·0003) and among neonates (GMTs: 10·7 [10·0 to 11·5] vs 9·4 [8·8 to 10·0] vs 8·1 [7·6 to 8·6], p<0·0001; seroprevalence: 13·4% [10·7 to 16·7] vs 8·7% [6·5 to 11·5] vs 6·1% [4·2 to 8·5], p=0·0002). Regardless of the A(H1N1)pdm09-specific strain, maternal antibodies could be transferred efficiently via the placenta (mean transfer ratios: 1·10 for SWL4204/09 vs 1·09 for SWL1277/16 vs 1·06 for SWL185/18; p=0·93). The A(H1N1)pdm09 strain-specific antibodies waned below the protective threshold of 1:40 within 2 months after birth. After maternal antibody waning, there were periodic increases and decreases in HAI antibody titres against three A(H1N1)pdm09 strains, and such increases were all significantly associated with a higher immune response to heterologous strains. Vaccination against the SWL4204/09 strain was associated with a poor response to the SWL185/18 strain (β-0·20, 95% CI -0·28 to -0·13; p<0·0001). INTERPRETATION:Our findings suggest low pre-existing immunity against influenza A(H1N1)pdm09 virus among unvaccinated Chinese adult female and paediatric populations. This evidence, together with the rapid decay of maternal antibodies and the observed cross-reactivity among different A(H1N1)pdm09 strains, highlights the importance of accelerating maternal and paediatric influenza vaccination in China. FUNDING:The Key Program of the National Natural Science Foundation of China. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

Characterizing the long-term kinetics of maternally derived and vaccine-induced measles immunity is critical for informing measles immunization strategies moving forward. Based on two prospective cohorts of children in China, we estimate that maternally derived immunity against measles persists for 2.4 months. Following two-dose series of measles-containing vaccine (MCV) at 8 and 18 months of age, the immune protection against measles is not lifelong, and antibody concentrations are extrapolated to fall below the protective threshold of 200 mIU/ml at 14.3 years. A catch-up MCV dose in addition to the routine doses between 8 months and 5 years reduce the cumulative incidence of seroreversion by 79.3–88.7% by the age of 6 years. Our findings also support a good immune response after the first MCV vaccination at 8 months. These findings, coupled with the effectiveness of a catch-up dose in addition to the routine doses, could be instrumental to relevant stakeholders when planning routine immunization schedules and supplemental immunization activities.

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 4 th-5 th ( 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 (trend χ2=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.

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

Background A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children. Methods Two population-based longitudinal cohorts in southern China were studied during 2013–2018. Participants were enrolled in autumn 2013, including 2475 children aged 1–9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated. Results The average maternal antibody transfer ratio was 0.88 (95% CI 0.80–0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9–2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64. Conclusions Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0–5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.

The clinical significance of FLAIR vascular hyperintensity (FVH), a marker of collateral circulation in ischaemic stroke, remains controversial. We hypothesised that the association between FVH and outcomes varies with the severity of leukoaraiosis (LA), another marker of collaterals, and that their combined significance may vary with time. We included 459 consecutive patients with middle cerebral artery (MCA) stroke. Proximal and distal FVHs were distinguished based on location. LA was divided into two grades, according to Fazekas scores of 0–2 and 3–6. Symptom-to-MRI time was divided into two categories: ≤ 14 days and ≥ 15 days. We found no difference in FVH proportion according to LA grade. Multivariate analysis revealed that LA and FVH status were independently associated with unfavourable outcomes (modified Rankin scale ≥ 2) in patients with symptom-to-MRI times ≤ 14 days (P = 0.008), but not in those with symptom-to-MRI times ≥15 days (P = 0.61). In the group with symptom-to-MRI times ≤14 days, patients with LA 3–6 and FVH(+) (OR, 3.044; 95% CI, 1.116–8.305) were more likely to have unfavourable clinical outcomes compared with patients with LA 0–2 and FVH(+) but not compared with those with LA 0–2 and FVH(−) or LA 3–6 and FVH(−). In addition, FVH location did not influence the relationship between FVH and outcomes. The association between FVH and outcomes was influenced by the degree of LA in the acute but not in the subacute and chronic stages of MCA infarction. FVH predicts clinical outcomes independently only in those with more extensive LA.

Objective: To analyze the survival time and to explore the releated factors of antiretroviral therapy among HIV/AIDS patients in LiangShan Prefecture, Sichuan Province for reduction of AIDS death rate. Methods: The retrospective research method was used to collect relevant information from the Management Database of Antiviral Treatment from the National AIDS Comprehensive Prevention Information System. The Kaplan-Meier method was used to describe the survival distribution and to analyze the survival time by single factor and the model of Cox proportional riskanalysis was performed to analyze the survival time of HARRT by multi-factors analysis. Results: Total 14 219 adults and young persons aged ≥15 HIV/AIDS patients received antiviral treatment from 2005 to 2015. The average age of all cases was (36.10±9.41) years old and 10 021 were males (70.5%). The main route of infection was intravenous drug use (61.0%, 8 678 cases). At the end of the observation, 10001 cases (70.3%) were still treated, and 1 425 cases (10.0%) died; Cox Regression analysis showed that female (0.67 (0.55-0.81)), route of sexual infection (0.67 (0.56-0.79)), baseline CD4+T lymphocyte count 200-350 (0.41 (0.35-0.47)) and ≥350 (0.28 (0.24-0.34)), was a protective factor in death. At the beginning of treatment, the patient is clinically staging stage Ⅱ (0.70 (0.58-0.84)) and abnormal BMI (1.75 (1.50-2.03)), is a risk factor for death (P<0.05). Conclusion: Early antiviral treatment is of great significance in improving the anti-viral treatment effect of AIDS. Compliance education should be further strengthened so as to enhance their knowledge. And it is feasible to enhance the effect of treatment through nutritional support for prolonging patients survival time and improving the quality of life.

This outbreak was caused by astrovirus serotype 4 and the main exposure mode was likely person to person and touching a contaminated water faucet. Recommendations included immediate isolation of cases, proper handling of vomits, with environmental disinfectants, and training in good hand washing for students and teachers. Moreover, the drinking water faucet should be disinfected daily.

BACKGROUND:Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS:We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS:Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION:EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING:National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

Background Diseases caused by human enteroviruses (EVs) are a major global public health problem. Thus, the effective diagnosis of all human EVs infections and the monitoring of epidemiological and ecological dynamic changes are urgently needed. Methods Based on two comprehensive virological surveillance systems of hand, foot and mouth disease (HFMD), real-time PCR and nested RT-PCR (RT-snPCR) methods based on the enteroviral VP1, VP4-VP2 and VP4 regions were designed to directly detect all human EVs serotypes in clinical specimens. Results The results showed that the proposed serotyping strategy exhibit very high diagnostic efficiency (Study 1: 99.9%; Study 2: 89.5%), and the variance between the study was due to inclusion of the specific Coxsackie virus A6 (CVA6) real-time RT-PCR and VP4 RT-snPCR in Study 1 but not Study 2. Furthermore, only throat swabs were collected and analyzed in Study 2, whereas in Study 1, if a specific EV serotype was not identified in the primary stool sample, other sample types (rectal swab and throat swab) were further tested where available. During the study period from 2013 to 2018, CVA6 became one of the main HFMD causative agents, whereas the level of enterovirus A71 (EV-A71) declined in 2017. Conclusion The findings of this study demonstrate the appropriate application of PCR methods and the combination of biological sample types that are useful for etiological studies and propose a molecular strategy for the direct detection of human EVs in clinical specimens associated with HFMD.

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.

BACKGROUND AND PURPOSE: FLAIR vascular hyperintensity has been recognized as a marker of collaterals in ischemic stroke, but the impact on outcome is still controversial. We hypothesized that the association between FLAIR vascular hyperintensity and outcome varies with time. MATERIALS AND METHODS: We included 459 consecutive patients with middle cerebral artery stroke and divided them into 3 groups by symptom-to-MR imaging time (group 1, <= 7 days; group 2, 8-14 days; group 3, >= 15 days). The FLAIR vascular hyperintensity score, ranging from 0 to 3 points, was based on territory distributions of different MCA segments. The associations between FLAIR vascular hyperintensity and outcome with time were analyzed qualitatively and quantitatively. RESULTS: No patients underwent MR imaging within 6 hours of onset. The proportion of FLAIR vascular hyperintensity (+) and severe stenosis or occlusion of MCA was not significantly dependent on time. In groups 1 and 2, FLAIR vascular hyperintensity (+) was significantly associated with larger lesions, the prevalence of flow injury, and unfavorable outcome (mRS >= 2). There were no such associations in group 3. Multiple logistic regressions demonstrated that FLAIR vascular hyperintensity (+) was an independent risk factor for unfavorable outcome in group 2. Infarction volume tended to increase with the increase of the distal FLAIR vascular hyperintensity score in groups 1 and 2, while declining in group 3. CONCLUSIONS: FLAIR vascular hyperintensity is associated with unfavorable outcome within 6 hours to 14 days of onset, while the wider distribution of distal FLAIR vascular hyperintensity may be favorable beyond 14 days of onset in MCA infarction. Symptom-to-MR imaging time should be considered when assessing the prognostic value of FLAIR vascular hyperintensity.

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.

Objective: To analyze the deaths with antiretroviral treatment among adult HIV/AIDS patients in Liangshan Yi Autonomous Prefecture from 2005 to 2015, in order to understand the epidemiological characteristics and to further reduce the mortality rate in Liangshan Prefecture. Methods: The relevant information was collected through the Management Database of Antiretroviral Treatment from the National AIDS Comprehensive Prevention Information System. Results: From 2005 to 2015, a total of 14 219 adult HIV/AIDS patients received antiretroviral treatment and 1 425 death cases were reported during the treatment. The cause of death was mainly AIDS-related diseases (58.9%), and the cumulative mortality rate was 10.02%. Gender, age, the way of infection, duration of antiretroviral therapy, clinical stage when received antiretroviral therapy, and CD(4)(+) T lymphocyte levels were factors for the mortality rate (P<0.001). The mortality increased with older age, higher initiation clinical stage and lower level of CD(4)(+) T lymphocyte. Among the death cases, 82.6% were male, 1 182 (82.9%) were married or cohabited, most aged between 30-39 years old (48.6%). At the initial point of receiving antiretroviral therapy, 49.7% of the cases with CD(4)(+)T lymphocytes levels< 200/μl, 61.2% of the deaths cases were>1 000 copies/ml during the last viral load test, and 16.2% of deaths were ≥500/μl in the last CD(4)(+)T lymphocyte test; 44.5% of deaths were received antiretroviral treatment within one year. Conclusion: Early and timely antiretroviral therapy should be carried out. It is necessary to strengthen the propaganda of antiretroviral therapy and to improve the management quality of follow-up information of antiretroviral therapy case files, and to improve the medication compliance of patients.

[This corrects the article DOI: 10.1371/journal.pone.0205500.].

Many surveillance systems of infectious diseases are syndrome-based, capturing patients by clinical manifestation. Only a fraction of patients, mostly severe cases, undergo laboratory validation to identify the underlying pathogen. Motivated by the need to understand transmission dynamics and associate risk factors of enteroviruses causing the hand, foot, and mouth disease (HFMD) in China, we developed a Bayesian spatio-temporal modeling framework for surveillance data of infectious diseases with small validation sets. A novel approach was proposed to sample unobserved pathogen-specific patient counts over space and time and was compared to an existing sampling approach. The practical utility of this framework in identifying key parameters was assessed in simulations for a range of realistic sizes of the validation set. Several designs of sampling patients for laboratory validation were compared with and without aggregation of sparse validation data. The methodology was applied to the 2009 HFMD epidemic in southern China to evaluate transmissibility and the effects of climatic conditions for the leading pathogens of the disease, enterovirus 71, and Coxsackie A16. Supplementary materials for this article are available online.

We conducted a retrospective analysis of norovirus outbreaks reported to the National Public Health Emergency Event Surveillance System (PHEESS) in China from January 1, 2014 to December 31, 2017. We reviewed all acute gastroenteritis outbreaks (n = 692) submitted to PHEESS to identify the frequency, seasonality, geographic distribution, setting, and transmission mode of outbreaks due to norovirus. A total of 616 norovirus outbreaks resulting in 30,848 cases were reported. Among these outbreaks, 571 (93%) occurred in school settings including 239 (39%) in primary schools, 136 (22%) in childcare facilities, and 121 (20%) in secondary schools. The majority of outbreaks (63%) were due to person-to-person transmission, followed by multiple modes of transmission (11%), foodborne (5%) and waterborne (3%) transmission. These findings highlight the importance of improving hand hygiene and environmental disinfection in high-risk settings. Developing a standard and quantitative outbreak reporting structure could improve the usefulness of PHEESS for monitoring norovirus outbreaks.

Objectives: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) were responsible for 43.3% (235 123/543 243) and 24.8% (134 607/543 243) of all laboratory-confirmed hand, foot and mouth disease (HFMD) cases during 2010-2015 in China. Three monovalent EV71 vaccines have been licensed in China while bivalent EV71/CA16 vaccines are under development. A comparative cost-effectiveness analysis of bivalent EV71/CA16 versus monovalent EV71 vaccination would be useful for informing the additional value of bivalent HFMD vaccines in China. Methods: We used a static model parameterized with the national HFMD surveillance data during 2010 -2013, virological HFMD surveillance records from all 31 provinces in mainland China during 2010-2013 and caregiver survey data of costs and health quality of life during 2012-2013. We estimated the threshold vaccine cost (TVC), defined as the maximum additional cost that could be paid for a cost-effective bivalent EV71/CA16 vaccine over a monovalent EV71 vaccine, as the outcome. The base case analysis was performed from a societal perspective. Several sensitivity analyses were conducted by varying assumptions governing HFMD risk, costs, discounting and vaccine efficacy. Results: In the base case, choosing the bivalent EV71/CA16 over monovalent EV71 vaccination would be cost-effective only if the additional cost of the bivalent EV71/CA16 compared with the monovalent EV71 vaccine is less than V4.7 (95% CI 4.2-5.2). Compared with the TVC in the base case, TVC increased by up to V8.9 if all the test-negative cases were CA16-HFMD; decreased by V1.1 with an annual discount rate of 6% and exclusion of the productivity loss; and increased by V0.14 and V0.3 with every 1% increase in bivalent vaccine efficacy against CA16-HFMD and differential vaccine efficacy against EV71-HFMD, respectively. Conclusions: Bivalent EV71/CA16 vaccines can be cost-effective compared with monovalent EV71 vaccines, if suitably priced. Our study provides further evidence for determining the optimal use of HFMD vaccines in routine paediatric vaccination programme in China. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.

In China pregabalin is the only one drug with Fibromyalgia (FM) indication approved China National Medical Products Administration (NMPA). While in clinical practice duloxetine are still often prescribed in FM treatment in China.This study is to adapt a developed FM pharmacoeconomics model to evaluate the cost-effectiveness of pregabalin compared with duloxetine by using Chinese data. A decision analytic model of cost and outcomes based on RCTs has been developed in 2010.Costs considered in this model included: drugs utilization, GP visits, diagnostic tests and referrals to specialists. Costs are presented in 2019 RMB. Outcomes considered are QALY gain and responder months. Treatment comparators and utilization patterns were provided through local physician questionnaires or internal dataset review. Fibromyalgia patients' health resources utilization rates and costs were localized by literature review, official health information platform search as well as internal data source analysis. China life tables data was provided by WHO. 3.5% was applied as the discount rate. According to a 3-years simulation, compared pregabalin 300mg with duloxetine 60mg, the incremental cost was 8,804.08RMB, the incremental responders were 5. The ICER(per QALY) would be 169,305.18RMB, which is less than 3 GDPs per capita (64644RMB *3). One way sensitive analysis (OWSA) showed. Pregabalin may be cost-effective compared with Duloxetine in China health care setting.