Health system barriers to timely routine measles vaccinations in rural southwest China: a qualitative study on the perspectives of township vaccination professionals and village doctors.

OBJECTIVES: A well-functioning health system ensures timely routine measles vaccinations for age-appropriate children, minimising measles risk. However, there is limited knowledge about the impact of the performance of immunisation programmes in health systems on the timeliness of measles vaccination. This study aimed to identify health system barriers to timely routine measles vaccination in rural southwest China, integrating the perspectives of township vaccination professionals and village doctors. DESIGN, SETTING AND PARTICIPANTS: Qualitative study among township vaccination professionals and village doctors in rural Guangxi, southwest China. METHODS: 20 focus group discussions (FGDs) at township level and 120 in-depth interviews (IDIs) at village level, based on a four-theme framework. We used convenience sampling to recruit 60 township vaccination professionals and 120 village doctors in 2015. Instruments used were a semistructured questionnaire and interview outlines. We collected township and village-level data focusing on themes of health resources allocation, pattern of vaccination services, management and supervision of vaccination services, and perceptions of vaccination policy. The FGDs and IDIs were audio-recorded and transcribed. Braun and Clarke's thematic analysis approach was adopted to synthesise findings into meaningful subthemes, narrative text and illustrative quotations. RESULTS: The health system barriers to timely routine vaccinations were explored across four themes. Barriers in the health resources allocation theme comprised (1) inadequacy of vaccination-related human resources (eg, lack of township vaccination professionals and lack of young village doctors), and (2) incompatible and non-identical information system of vaccination services across regions. Barriers in the pattern of vaccination services theme included inflexible vaccination services models, for example, routine vaccination services being offered monthly on fixed vaccination days, limited numbers of vaccination days per month, vaccination days being set on non-local market days, vaccination days being clustered into a specific period and absence of formal vaccination appointments. Ineffective economic incentive mechanism was identified as a barrier in the management and supervision of vaccination services theme. Low-degree participation of village doctors in routine vaccination services was identified as a barrier in the perceptions of vaccination policy theme. CONCLUSIONS: We encourage policymakers and stakeholders to apply these findings to improve the timeliness of routine vaccination. Barriers to timely routine vaccination include inadequate allocation of vaccination-related resources and inflexible vaccination service delivery models. Financial and non-financial incentives should be used to retain and recruit vaccination professionals and village doctors. Strengthening information systems with unified data standards enables cross-regional data exchange. Optimising immunisation services and rationalising vaccination days could eliminate health system barriers and improve vaccination timeliness in rural China.

Safety of primary immunization using inactivated SARS-CoV-2 vaccine (CoronaVac®) among population aged 3 years and older in a large-scale use: A multi-center open-label study in China.

OBJECTIVE: To evaluate the safety of primary immunization using CoronaVac® among population aged 3 years and above in a large-scale use. METHOD: A multi-center open-label study was carried out in 11 provinces of China. Individuals aged 3 years and older who had no history of COVID-19 vaccination or had received only one dose of CoronaVac® were enrolled in this study. Adults and elderly with or without underlying medical conditions(UMCs) were also recruited. Eligible participants received one or two doses of CoronaVac® with an interval of 28 days. Demographic information, vaccination and the occurrence of adverse events were recorded by participants or guardians using data collection system designed for this study. All adverse events occurred within 6 months after the second dose of vaccination were collected. The incidence of adverse events that cannot be ruled out as being caused by the vaccine were calculated to assess the safety of CoronaVac®. This study is registered with ClinicalTrials. Gov (NCT04911790 and NCT04992208). RESULTS: A total of 162,691 participants have been included in this study and 89.50 % had finished primary immunization. Among adults and elderly, people with UMCs accounted for 25.85 %, with the top five disease being hypertension, diabetes, chronic gastritis, coronary heart disease(CHD) and kidney stone. The overall incidence of adverse reactions (ARs) within 6 months after the second vaccination was 2.70 %, with incidence for children and adolescents, adults, and elderly being 2.03 %, 3.46 %, and 1.90 %, respectively. Most ARs were mild (grade 1). Pain at the injection sites, fatigue, induration/swelling, and headache were the most common symptoms, occurring in 1.64 %, 0.46 %, 0.31 % and 0.24 %, respectively. No serious adverse events related to vaccines were reported. No adverse events of special interest (AESIs) were identified. For children and adolescents, children aged 3-5 years had the highest incidence of ARs of 3.29 %. The incidence of ARs among those aged 18 years and older with and without UMCs were 2.81 % and 2.99 %, respectively, with no statistical significance between two groups(P = 0.089). And people with coronary heart disease had higher AR incidence compared to those with other UMCs, but the most common symptoms was pain at the injection site. CONCLUSION: CoronaVac® is safe in a large-scale use and shows well-tolerance for children and adolescents and people with underlying medical conditions. Further studies need to be conducted to explore the relation of ARs incidence to age or different kinds of UMCs.

Multi-level determinants of failure to receive timely and complete measles vaccinations in Southwest China: a mixed methods study.

BACKGROUND: Measles outbreaks re-emerged in 2013-2014 in Guangxi Zhuang Autonomous Region of China, where measles immunisation coverage is high. The discrepancy between the vaccination coverage and outbreaks indicates that timeliness is crucial, yet there is limited knowledge on the health system barriers to timely vaccination. Using integrated evidence at the household, village clinic, and township hospital levels, this study aimed to identify the determinants of failure in receiving timely measles vaccinations among children in rural Guangxi. METHODS: A multi-stage stratified cluster sampling survey with a nested qualitative study was conducted among children aged 18-54 months in Longan, Zhaoping, Wuxuan, and Longlin counties of Guangxi from June to August 2015. The status of timely vaccinations for the first dose of measles-containing vaccine (MCV1) and the second dose of measles-containing vaccine (MCV2) was verified via vaccination certificates. Data on household-level factors were collected using structured questionnaires, whereas data on village and township-level factors were obtained through in-depth interviews and focus group discussions. Determinants of untimely measles vaccinations were identified using multilevel logistic regression models. RESULTS: A total of 1216 target children at the household level, 120 villages, and 20 township hospitals were sampled. Children were more likely to have untimely vaccination when their primary guardian had poor vaccination knowledge [MCV1, odds ratio (OR) = 1.72; MCV2, OR = 1.51], had weak confidence in vaccines (MCV1, OR = 1.28-4.58; MCV2, OR = 1.42-3.12), had few practices towards vaccination (MCV1, OR = 12.5; MCV2, OR = 3.70), or had low satisfaction with vaccination service (MCV1, OR = 2.04; MCV2, OR = 2.08). This trend was also observed in children whose village doctor was not involved in routine vaccination service (MCV1, OR = 1.85; MCV2, OR = 2.11) or whose township hospital did not provide vaccination notices (MCV1, OR = 1.64; MCV2, OR = 2.05), vaccination appointment services (MCV1, OR = 2.96; MCV2, OR = 2.74), sufficient and uniformly distributed sessions for routine vaccination (MCV1, OR = 1.28; MCV2, OR = 1.17; MCV1, OR = 2.08), or vaccination service on local market days (MCV1, OR = 2.48). CONCLUSIONS: Guardians with poor knowledge, weak beliefs, and little practice towards vaccination; non-involvement of village doctors in routine vaccinations; and inconvenient vaccination services in township hospitals may affect timely measles vaccinations among children in rural China.

Timeliness, completeness, and timeliness-and-completeness of serial routine vaccinations among rural children in Southwest China: A multi-stage stratified cluster sampling survey.

INTRODUCTION: Vaccination coverage is widely used as metric of vaccination programme performance. However, VPDs outbreaks were reported in areas with high vaccination coverage. Timeliness and completeness have been considered more important assessment indicators of routine vaccination than overall vaccination coverage, but little is known in rural China. This study aimed to assess the timeliness and completeness of serial routine vaccinations among children in rural Southwest China. METHODS: A multi-stage stratified cluster survey was conducted among 1062 children aged 18-48 months in rural Guangxi. Vaccination status was obtained from child's vaccination certificate. We calculated timely vaccination coverage, complete vaccination coverage, timely-and-complete vaccination coverage and 95% CI for routine vaccination through weighted estimation analysis. Weighted Kaplan-Meier analyses were applied to estimate the median delay periods for each dose of serial routine vaccines, including one-dose BCG, three-dose HepB, three-dose OPV, four-dose DTP, two-dose MCV, two-dose JEV and two-dose MPV-A. Complete coverage, and timely-and-complete coverage for combined 5-vaccine series were calculated. RESULTS: For each dose of routine vaccines, overall vaccination coverages were over 90%, but timely vaccination coverage ranged from the lowest of 44.4% for JEV1 to the highest of 92.5% for MPV-A1. For multi-dose routine vaccines, complete vaccination coverages varied from the lowest of 92.9% for MCV to the highest of 100% for HepB, and timely-and-complete vaccination coverages were lower than 80%, ranging from the lowest of 30% for JEV to the highest of 77.2% for MPV-A. For combined 5-vaccine series, complete coverage was 77%, while timely-and-complete coverage was 12.1%. MPV-A1 had the longest median delay of 176 days, but BCG and HepB1 had the shortest of 1 day. CONCLUSIONS: The overall coverages of serial routine vaccinations were high, but the timeliness and completeness were poor. Relevant agencies of vaccination service should address timeliness-and-completeness into the assessment indicators of routine vaccination service quality.

Importation of Mumps Virus Genotype K to China from Vietnam.

During May-August 2016, mumps virus genotype K was detected in 12 Vietnam citizens who entered China at the Shuikou border crossing and 1 girl from China. We provide evidence that mumps genotype K is circulating in Vietnam and was imported to China from Vietnam.

Properties of hydrodynamic J-type countercurrent chromatography for protein separation using aqueous two-phase systems: With special reference to constructing conical columns.

Protein separation using hydrodynamic countercurrent chromatography (CCC), where low backpressure is inherent, is more challenging, more time consuming and more costly when compared with separating small molecules. The most hopeful approach is to rationally design suitable columns for already commercialized J-type CCC machinery. By comparing 3 column geometries (3D helix, 2D spiral and 3D cone), we firstly constructed the mechanical model tailored to the conical column on J-type CCC using aqueous two-phase system (ATPS) on protein separation. Aimed at mechanistically understanding hydrodynamic CCC, we then developed a semi-quantitative model to account for contributions of both hydrodynamic and hydrostatic forces to stationary phase retention, and have subsequently compared the modelling outcomes with experimental results. We practiced a methodology to delineate both phase mixing and stationary phase retention before committing to physically constructing CCC columns. Following theoretical analyses, we finally constructed conical columns for J-type CCC. Using model proteins (myoglobin and lysozyme) and with 2 ATPSs containing PEG1000 and phosphate, sound protein separation has been achieved (resolution reaches 1.5-2.0 and stationary phase retention also exceeds 40%) for the selected ATPSs and under a varied level of sample volumes and loadings.

Spatial, temporal and spatio-temporal clusters of measles incidence at the county level in Guangxi, China during 2004-2014: flexibly shaped scan statistics.

BACKGROUND: Outbreaks of measles re-emerged in Guangxi province during 2013-2014, where measles again became a major public health concern. A better understanding of the patterns of measles cases would help in identifying high-risk areas and periods for optimizing preventive strategies, yet these patterns remain largely unknown. Thus, this study aimed to determine the patterns of measles clusters in space, time and space-time at the county level over the period 2004-2014 in Guangxi. METHODS: Annual data on measles cases and population sizes for each county were obtained from Guangxi CDC and Guangxi Bureau of Statistics, respectively. Epidemic curves and Kulldorff's temporal scan statistics were used to identify seasonal peaks and high-risk periods. Tango's flexible scan statistics were implemented to determine irregular spatial clusters. Spatio-temporal clusters in elliptical cylinder shapes were detected by Kulldorff's scan statistics. Population attributable risk percent (PAR%) of children aged ≤24 months was used to identify regions with a heavy burden of measles. RESULTS: Seasonal peaks occurred between April and June, and a temporal measles cluster was detected in 2014. Spatial clusters were identified in West, Southwest and North Central Guangxi. Three phases of spatio-temporal clusters with high relative risk were detected: Central Guangxi during 2004-2005, Midwest Guangxi in 2007, and West and Southwest Guangxi during 2013-2014. Regions with high PAR% were mainly clustered in West, Southwest, North and Central Guangxi. CONCLUSIONS: A temporal uptrend of measles incidence existed in Guangxi between 2010 and 2014, while downtrend during 2004-2009. The hotspots shifted from Central to West and Southwest Guangxi, regions overburdened with measles. Thus, intensifying surveillance of timeliness and completeness of routine vaccination and implementing supplementary immunization activities for measles should prioritized in these regions.

Timeliness and completeness of measles vaccination among children in rural areas of Guangxi, China: A stratified three-stage cluster survey.

BACKGROUND: Large-scale outbreaks of measles occurred in 2013 and 2014 in rural Guangxi, a region in Southwest China with high coverage for measles-containing vaccine (MCV). This study aimed to estimate the timely vaccination coverage, the timely-and-complete vaccination coverage, and the median delay period for MCV among children aged 18-54 months in rural Guangxi. METHODS: Based on quartiles of measles incidence during 2011-2013, a stratified three-stage cluster survey was conducted from June through August 2015. Using weighted estimation and finite population correction, vaccination coverage and 95% confidence intervals (CIs) were calculated. Weighted Kaplan-Meier analyses were used to estimate the median delay periods for the first (MCV1) and second (MCV2) doses of the vaccine. RESULTS: A total of 1216 children were surveyed. The timely vaccination coverage rate was 58.4% (95% CI, 54.9%-62.0%) for MCV1, and 76.9% (95% CI, 73.6%-80.0%) for MCV2. The timely-and-complete vaccination coverage rate was 47.4% (95% CI, 44.0%-51.0%). The median delay period was 32 (95% CI, 27-38) days for MCV1, and 159 (95% CI, 118-195) days for MCV2. CONCLUSIONS: The timeliness and completeness of measles vaccination was low, and the median delay period was long among children in rural Guangxi. Incorporating the timeliness and completeness into official routine vaccination coverage statistics may help appraise the coverage of vaccination in China.

Parental migration and children's timely measles vaccination in rural China: a cross-sectional study.

OBJECTIVE: With the rapid economic development in China, millions of rural residents are migrating to the cities to gain employment, resulting in numerous left-behind children (LBC). Simultaneously, outbreaks of measles continue to occur, yet the effect of parental migration on children's vaccination status is largely unknown. This study aimed to evaluate the association between parental migration and children's timely measles vaccination in rural China, after adjusting for family socio-economic status (SES) indicators. METHODS: We conducted a cross-sectional survey using multistage sampling among children aged 18-54 months in rural Guangxi of China. Information on measles vaccination status was obtained from the child's vaccination certificate, and data on SES were collected by interviewing the child's primary guardian. Family SES and vaccination coverage were compared between LBC and non-left-behind children (NLBC) using weighted logistic regression, while the delay in vaccination was compared using Kaplan-Meier survival analysis. RESULTS: Of the 1216 study children, 46% were LBC and 54% were NLBC. Compared to NLBC, the coverage of timely measles vaccination was significantly lower, and the median delay period was longer among LBC. After adjusting for SES indicators, LBC were significantly more likely to have an untimely vaccination for their first dose of measles vaccine than NLBC (OR = 1.33, 95% CI = 1.02-1.75). CONCLUSIONS: Due to the negative effect of parental migration and family SES, LBC were more likely to encounter serious delays of measles vaccination in rural China. Optimising vaccination policies could facilitate timely vaccination among LBC in rural China.

Spread of Neisseria meningitidis serogroup W clone, China.

During February 2011-June 2012, invasive infection with Neisseria meningitidis serogroup W was identified in 11 persons in southeastern China. All isolates tested had matching or near-matching pulsed-field gel electrophoresis patterns and belonged to multilocus sequence type 11. The epidemiologic investigation suggested recent transmission of this clonal complex in southeastern China.

Purification of salvianolic acid B from the crude extract of Salvia miltiorrhiza with hydrophilic organic/salt-containing aqueous two-phase system by counter-current chromatography.

Establishment of hydrophilic organic/salt-containing aqueous two-phase system and purification of salvianolic acid B from crude extract of S. miltiorrhiza by counter-current chromatography with said system were studied. Ethanol and n-propanol were selected to constitute biphasic systems with ammonia sulphate, sodium chloride and phosphate separately, and related system characteristics including phase diagrams, phase ratio, separation time were tested. The partition coefficient of crude salvianolic acid B was also tested in above systems and further finely adjusted by altering the constitution of phosphate in n-propanol/phosphate system. Salvianolic acid B was purified to 95.5% purity by counter-current chromatography in 36% (w/w) n-propanol/8% (w/w) phosphate system with the ratio between dipotassium hydrogen phosphate and sodium dihydrogen phosphate of 94:6. One hundred and eight milligrams of salvianolic acid B was purified from 285 mg crude extract with the recovery of 89%.

One-step purification of alpha-amylase from the cultivation supernatant of recombinant bacillus subtilis by high-speed counter-current chromatography with aqueous polymer two-phase systems.

Purification of alpha-amylase from the cultivation supernatant of recombinant Bacillus subtilis by high-speed counter-current chromatography (HSCCC) in polyethylene glycol (PEG) 4000-inorganic salt aqueous polymer two-phase systems was studied. The effects of sodium chloride concentration on the partition coefficients of alpha-amylase and total protein were respectively tested in PEG4000-phosphate and PEG4000-citrate aqueous polymer two-phase systems to find the proper range of sodium chloride concentration for the HSCCC purification of alpha-amylase. Alpha-amylase was purified from the cultivation supernatant by HSCCC in PEG4000-phosphate system containing 2% (w/w) sodium chloride, yet with considerable loss of activity. PEG4000-citrate aqueous polymer two-phase system containing 2% (w/w) sodium chloride and supplemented with 0.56% (w/w) CaCl2 as protective agent was then successfully applied to purify alpha-amylase from cultivation supernatant by HSCCC to homogeneity and significantly increased the recovery of alpha-amylase activity from around 30 to 73.1%.

[Separation of proteins in aqueous two-phase systems with high-speed counter-current chromatography].

High-speed counter-current chromatography (HSCCC) is a continuous liquid-liquid partition chromatography, with remarkable advantages of high separation efficiency and no adsorption or denaturation by solid phase. The retention of stationary phase and the separation of proteins in polyethylene glycol 1000 (PEG1000)-phosphate aqueous two-phase system (ATPs) were studied with a multi-column high speed-counter-current chromatograph. The flow direction and speed of the mobile phase, and the rotation direction and speed of the apparatus showed different effects on the retention of the stationary phase, which reached the maximum at 33.3% with a flow rate of 0.6 mL/min and a rotation speed of 900 r/min in 14.0% PEG1000-16.0% phosphate ATPs. Distinct differences in partition coefficients among cytochrome C, lysozyme and hemoglobin were found at pH 9.2 and these three proteins were successfully separated in 14.0% PEG1000-16.0% phosphate ATPs at pH 9.2 by HSCCC with the apparatus rotating at 850 r/min and the mobile phase flow rate of 1.0 mL/min. The major protein components in hen egg white, including ovaltransferrin, ovalbumin and lysozyme also show distinct differences of partition coefficients in PEG1000-phosphate ATPs at pH 9.2. Ovalbumin and lysozyme were successfully purified to homogeneity and ovaltransferrin to ca 60% purity from the hen egg white sample with yields over 90% in 15.0% PEG1000-17.0% phosphate ATPs at pH 9.2 with the apparatus rotating at 850 r/min and mobile phase flow rate of 1.0 mL/min.

[Purification of ovalbumin from hen egg white by high-speed counter-current aqueous two-phase chromatography].

High-speed counte-recurrent chromatography (HSCCC) is a continuous liquid-liquid partition chromatography without solid matrix, which has the significant features of high resolution and high recovery. The separation of bio-macromolecule in aqueous two-phase systems (ATPs) with HSCCC is still under research, and the establishment of high-speed counter-current aqueous two-phase chromatography (HSCCC-ATP) relies on the improvement of equipment structure and optimization of operation parameters. By using a multi-column high-speed counter-current chromatograph, the separation of protein mixture and the purification of ovalbumin from hen egg white were studied. The effects of pH and PEG concentration on the partition coefficients of proteins were tested in PEG1000-phosphate ATPs, and distinct differences among partition coefficients of proteins were found at pH 9.2 and 15.0% (W/W) PEG concentration in said system. The separation of protein mixture, consisting of cytochrome C, lysozyme and myoglobin was successfully performed in 15.0% (W/W) PEG1000-17.0% (W/W) potassium phosphate ATPs at pH 9.2 with high-speed counter-current chromatograph at rotation speed of 850r/min and flow rate of 0.8mL/min, using upper phase as stationary phase. pH and PEG concentration also had distinct effects on the partition coefficients of the major protein components in hen egg white, including ovaltransferrin, ovalbumin and lysozyme. The optimal pH value and PEG concentration for the purification of ovalbumin by HSCCC-ATP were found to be 9.2 and 16.0% (W/W) respectively. Ovalbumin was successfully purified to homogeneity from the hen egg white sample in 16.0% (W/W) PEG1000-17.0% (W/W) potassium phosphate ATPs at pH 9.2 with high-speed counter-current chromatograph at rotation speed of 850r/min and flow rate of 1.8mL/min, using upper phase as stationary phase. The purification recovery of ovalbumin was around 95%.