An Observational Prospective Cohort Study of Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection of an Aerosolized, Inhaled Adenovirus Type 5-Vectored Coronavirus Disease 2019 Vaccine Given as a Second Booster Dose in Guangzhou City, China.

Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Real-world effectiveness and factors associated with effectiveness of inactivated SARS-CoV-2 vaccines: a systematic review and meta-regression analysis.

BACKGROUND: The two inactivated SARS-CoV-2 vaccines, CoronaVac and BBIBP-CorV, have been widely used to control the COVID-19 pandemic. The influence of multiple factors on inactivated vaccine effectiveness (VE) during long-term use and against variants is not well understood. METHODS: We selected published or preprinted articles from PubMed, Embase, Scopus, Web of Science, medRxiv, BioRxiv, and the WHO COVID-19 database by 31 August 2022. We included observational studies that assessed the VE of completed primary series or homologous booster against SARS-CoV-2 infection or severe COVID-19. We used DerSimonian and Laird random-effects models to calculate pooled estimates and conducted multiple meta-regression with an information theoretic approach based on Akaike's Information Criterion to select the model and identify the factors associated with VE. RESULTS: Fifty-one eligible studies with 151 estimates were included. For prevention of infection, VE associated with study region, variants, and time since vaccination; VE was significantly decreased against Omicron compared to Alpha (P = 0.021), primary series VE was 52.8% (95% CI, 43.3 to 60.7%) against Delta and 16.4% (95% CI, 9.5 to 22.8%) against Omicron, and booster dose VE was 65.2% (95% CI, 48.3 to 76.6%) against Delta and 20.3% (95% CI, 10.5 to 28.0%) against Omicron; primary VE decreased significantly after 180 days (P = 0.022). For the prevention of severe COVID-19, VE associated with vaccine doses, age, study region, variants, study design, and study population type; booster VE increased significantly (P = 0.001) compared to primary; though VE decreased significantly against Gamma (P = 0.034), Delta (P = 0.001), and Omicron (P = 0.001) compared to Alpha, primary and booster VEs were all above 60% against each variant. CONCLUSIONS: Inactivated vaccine protection against SARS-CoV-2 infection was moderate, decreased significantly after 6 months following primary vaccination, and was restored by booster vaccination. VE against severe COVID-19 was greatest after boosting and did not decrease over time, sustained for over 6 months after the primary series, and more evidence is needed to assess the duration of booster VE. VE varied by variants, most notably against Omicron. It is necessary to ensure booster vaccination of everyone eligible for SARS-CoV-2 vaccines and continue monitoring virus evolution and VE. TRIAL REGISTRATION: PROSPERO, CRD42022353272.

Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Health and Economic Evaluation of Vaccination Against Pertussis in China: A 40-Year Analysis.

OBJECTIVES: This study aimed to evaluate the health and economic impact of diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) and diphtheria-tetanus-acellular pertussis vaccine (DTaP) vaccination on pertussis prevention and control in China during the 40 years from 1978 to 2017. METHODS: We conducted cost-benefit analyses with a decision tree model populated with historical vaccination coverage levels and pertussis incidence and mortality data from before 1978 and during 1978 to 2017. We modeled 40 birth cohorts from birth until death. Costs and benefits were estimated from direct cost and societal perspectives (direct and indirect costs). Costs and benefits were adjusted to 2017 US dollars (USD), and future values were discounted at a 3% annual rate. We calculated net benefit values (net savings) and benefit-cost ratios of pertussis vaccination of children younger than 5 years. We conducted sensitivity analyses by varying key parameters within plausible ranges. RESULTS: Without DTwP and DTaP vaccination, there would be an estimated 115.76 million pertussis cases and 426 650 pertussis deaths in the 40 cohorts. With DTwP/DTaP vaccination, pertussis cases and deaths were decreased by an estimated 92.57% and 97.43%, saving 46 987.81 million USD in direct costs and 82 013.37 million USD from societal perspective. Pertussis vaccination program costs were 2168.76 million USD and 3961.28 million USD from direct cost and societal perspectives. Benefit-cost ratios were 21.67:1 from the direct cost perspective and 20.70:1 from the societal perspective. Sensitivity analyses showed the results to be robust. CONCLUSIONS: Over the lifetime of 40 birth cohorts, China's immunization program is preventing 93% of pertussis cases and 97% of pertussis deaths, resulting in substantial savings to the healthcare system and society.

Multiple rib and vertebral fractures associated with Bordetella pertussis infection: a case report.

BACKGROUND: Pertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis, characterized by paroxysms of severe coughing, and predominantly affects children. We report the first case of multiple fractures in the ribs, lumbar spine, and sacrum associated with severe coughing caused by Bordetella pertussis infection in an adult. CASE PRESENTATION: A 49-year-old female presented with acute-onset chest wall pain for 3 weeks. Imaging results revealed multiple fractures in the ribs and vertebrae, as well as bilateral pleural effusion, pericardial effusion, right pneumothorax, and enlargement of the left parapharyngeal and subclavian lymph nodes. The patient's bone density scan, autoimmune antibodies, bone marrow biopsy, and sacral bone biopsy all came back normal. Imaging test results found no evidence of solid tumors or active TB infection. The patient later recalled having violent coughing prior to the onset of chest pain and several family members having similar symptoms. Her blood sample was sent to the CDC, revealing Bordetella pertussis toxin (PT) IgG titer of 110.68 IU/mL. The patient was diagnosed with pertussis and multiple stress fractures from violent coughing. Symptomatic treatments were administered, and the patient's symptoms improved. The patient was followed up 8 weeks later, she reported no more coughing or chest pain. CONCLUSIONS: Pertussis is not just a pediatric disease, but diagnosis in adults is challenging as patients may present with a myriad of confusing symptoms, such as multiple stress fractures due to violent coughing. Medical and epidemiological histories are key to reaching the correct diagnosis, which is essential for appropriate treatments to avoid further complications. Adult immunization should be suggested both for the protection of the adult population and to prevent transmission to children.

Changing Epidemiology of Hepatitis A in China: Evidence From Three National Serological Surveys and the National Notifiable Disease Reporting System.

BACKGROUND AND AIMS: China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine. APPROACH AND RESULTS: Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after >10 years of private sector vaccination, HepA coverage was <30% among children <5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was >90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts. CONCLUSIONS: The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.

Detection of a Highly Divergent Type 3 Vaccine-Derived Poliovirus in a Child with a Severe Primary Immunodeficiency Disorder - Chongqing, China, 2022.

Oral poliovirus vaccine (OPV) has proven to be highly effective in the global effort to eradicate poliomyelitis because of its ability to induce both humoral and intestinal immunity, ease of administration, and low cost (1). Sabin-strain OPV contains live attenuated virus and induces immunity by replicating in the intestinal tract, triggering an immune response that clears the vaccine virus. However, among undervaccinated communities and persons with immunodeficiency, OPV mutations that arise during prolonged replication can result in the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs). In addition, OPV has resulted in rare cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccine recipients or their close contacts (1). Identification of circulating polioviruses relies on surveillance of acute flaccid paralysis (AFP) and environmental surveillance of wastewater (i.e., sewage). In 2022, type 3 VDPV (VDPV3) was detected in stool specimens from an infant with primary immunodeficiency disorder (PID) through a pilot surveillance program to identify VDPVs in children with PIDs. Integrated AFP, environmental, and immunodeficiency-associated VDPV (iVDPV) surveillance is critical to detecting and containing all polioviruses and achieving the goal of global polio eradication.

Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations.

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.

National and provincial impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in China: a modeling analysis.

BACKGROUND: Globally, Haemophilus influenzae type b (Hib) vaccine has substantially reduced the burden of Hib invasive disease. However, China remains the only country not to include Hib vaccine into its national immunization program (NIP), although it accounts for 11% of global Hib deaths. We aimed to assess the cost-effectiveness of including Hib vaccine in China's NIP at the national and provincial levels. METHODS: Using a decision-tree Markov state transition model, we estimated the cost-effectiveness of Hib vaccine in the NIP compared to the status quo of Hib vaccine in the private market for the 2017 birth cohort. Treatment costs and vaccine program costs were calculated from Chinese Center for Disease Control and Prevention (CDC) and national insurance databases. Epidemiological data and other model parameters were obtained from published literature. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICER) were predicted by province. Deterministic and probabilistic sensitivity analyses were performed to explore model uncertainty. RESULTS: Including Hib vaccine in the NIP was projected to prevent approximately 2700 deaths (93% reduction) and 235,700 cases of Hib disease (92% reduction) for the 2017 birth cohort at the national level. Hib vaccine was cost-effective nationally (US$ 8001 per QALY gained) compared to the GDP per capita and cost-effective in 15 of 31 provinces. One-way and scenario sensitivity analyses indicated results were robust when varying model parameters, and in probabilistic sensitivity analysis, Hib vaccine had a 64% probability of being cost-effective nationally. CONCLUSION: Introducing Hib vaccine in China's NIP is cost-effective nationally and in many provinces. Less socioeconomically developed provinces with high Hib disease burden and low access to Hib vaccine in the current private market, such as those in the west region, would benefit the most from adding Hib vaccine to the NIP. In the absence of a national policy decision on Hib vaccine, this analysis provides evidence for provincial governments to include Hib vaccine into local immunization programs to substantially reduce disease burden and treatment costs.

Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies.

BACKGROUND: The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China. METHODS: During 2014-2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed. RESULTS: (1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group. CONCLUSIONS: HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

Using a hepatitis B surveillance system evaluation in Fujian, Hainan, and Gansu provinces to improve data quality and assess program effectiveness, China, 2015.

BACKGROUND: Monitoring hepatitis B surveillance data is important for evaluating progress towards global hepatitis B elimination goals. Accurate classification of acute and chronic hepatitis infections is essential for assessing program effectiveness. METHODS: We evaluated hepatitis B case-reporting at six hospitals in Fujian, Hainan and Gansu provinces in 2015 to assess the accuracy of case classification. We linked National Notifiable Disease Reporting System (NNDRS) HBV case-reports with hospital information systems and extracted information on age, gender, admission ward and viral hepatitis diagnosis from medical records. To assess accuracy, we compared NNDRS reported case-classifications with the national HBV case definitions. Multivariable logistic regression was used to identify factors associated with misclassification. RESULTS: Of the 1420 HBV cases reported to NNDRS, 23 (6.5%) of the 352 acute reports and 648 (60.7%) of the 1068 chronic reports were correctly classified. Of the remaining, 318 (22.4%) were misclassified and 431 (30.4%) could not be classified due to the lack of supporting information. Based on the multivariable analysis, HBV cases reported from Hainan (aOR = 1.8; 95% CI: 1.3-2.4) and Gansu (aOR = 12.7; 95% CI: 7.7-20.1) along with reports from grade 2 hospitals (aOR = 1.6; 95% CI:1.2-2.2) and those from non-HBV related departments (aOR = 5.3; 95% CI: 4.1-7.0) were independently associated with being 'misclassified' in NNDRS. CONCLUSIONS: We identified discrepancies in the accuracy of HBV case-reporting in the project hospitals. Onsite training on the use of anti-HBc IgM testing as well as on HBV case definitions and reporting procedures are needed to accurately assess program effectiveness and ensure case-patients are referred to appropriate treatment and care. Routine surveillance evaluations such as this can be useful for improving data quality and monitoring program effectiveness.

Progress Toward Measles Elimination - China, January 2013-June 2019.

In 2005, the World Health Organization (WHO) Western Pacific Region countries, including China, resolved to eliminate measles by 2012 or as soon as feasible thereafter (1). As of 2018, nine* of the 37 Western Pacific Region countries or areas† had eliminated§ measles. China's Measles Elimination Action Plan 2006-2012 included strengthening routine immunization; conducting measles risk assessments, followed by supplementary immunization activities (SIAs) with measles-containing vaccine (MCV) at national and subnational levels; strengthening surveillance and laboratory capacity; and investigating and responding to measles outbreaks. Most recently, progress toward measles elimination in China was described in a 2014 report documenting measles elimination efforts in China during 2008-2012 and a resurgence in 2013 (2). This report describes progress toward measles elimination in China during January 2013-June 2019.¶ Measles incidence per million persons decreased from 20.4 in 2013 to 2.8 in 2018; reported measles-related deaths decreased from 32 in 2015 to one in 2018 and no deaths in 2019 through June. Measles elimination in China can be achieved through strengthening the immunization program's existing strategy by ensuring sufficient vaccine supply; continuing to improve laboratory-supported surveillance, outbreak investigation and response; strengthening school entry vaccination record checks; vaccinating students who do not have documentation of receipt of 2 doses of measles-rubella vaccine; and vaccinating health care professionals and other adults at risk for measles.

Self-motivated medical care-seeking behaviors and disease progression in a community-based cohort of chronic hepatitis B virus-infected patients in China.

BACKGROUND: To determine the treatment behaviors among a community-based cohort of chronic hepatitis B virus (HBV)-infected persons and to examine the disease progression among non-antiviral-treated HBV-infected cases after 5 years of follow-up. METHODS: We conducted a community-based prospective study on people with chronic HBV infection in mainland China from 2009 to 2014. In 2009, we recruited participants who were identified as HBV infected in 2006 in a national sero-survey. A face-to-face follow-up investigation was completed in 2014, and the personal information, the clinical diagnosis provided at the last hospital visit, the HBV antiviral treatment history, and the insurance type was collected for each patient for analysis. Multivariable logistic regression was used to identify factors that are associated with active medical care- seeking and antiviral treatments. RESULTS: Among the 2422 chronic HBV-infected patients recruited in 2009, 1784 (73.7%) were followed-up to 2014, and 638 (35.8%) had sought medical care in hospitals; among them, 140 (21.9%) received antiviral treatments. The lowest medical care-seeking rate (26%) was in participants over 50-year old. We determined that the frequency of medical care-seeking was higher among those participants living in urban areas (aRR = 1.3, 95% CI:1.0-1.6), those in 0-19-year old (aRR = 1.5, 95% CI:1.1-2.1), 20-39-year old (aRR = 2.2, 95% CI:1.7-3.0) and 40-49-year old (aRR = 1.5, 95% CI:1.1-2.0), and persons with insurance of the type Urban residents' basic medical insurance (URBMI) or Commercial health insurance (CHI) (aRR = 2.5, 95% CI:1.7-3.6) and New Rural Cooperative Medical System (NRCMS) (aRR = 1.9, 95% CI:1.4-2.6). Patients were more likely to receive antiviral treatment if they were 20-39-year old (aRR = 0.4, 95% CI:0.3-0.7), had insurance of the type URBMI or CHI (aRR = 2.6, 95% CI:1.1-6.3) or NRCMS (aRR = 3.0, 95% CI:1.3-6.9) and were treated at prefecture and above-level hospitals (aRR = 2.0, 95% CI:1.4-3.0). Among non-antiviral-treated HBV-infected cases, we found the annual rates for HBsAg sero-clearance, progress to cirrhosis and HCC were 1.0, 0.6 and 0.2%, respectively. CONCLUSION: The rates of medical care-seeking and antiviral treatment were low among community-based chronic HBV-infected persons, thus we recommend improving the insurance policies for HBV-infected persons to increase the antiviral treatment rate, and conducting extensive education to promote HBV-infected patients actively seeking medical care from hospitals.

Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China.

China's hepatitis B virus (HBV) prevention policy has been evaluated through nationally representative serologic surveys conducted in 1992 and 2006. We report results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in the context of program policy. The 2014 survey used a 2-stage sample strategy in which townships were selected from 160 longstanding, nationally representative, county-level disease surveillance points, and persons 1-29 years of age were invited to participate. The 2014 sample size was 31,713; the response rate was 83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of age, the decline was 97%. China's HBV prevention program, targeted toward interrupting perinatal transmission, has been highly successful and increasingly effective. However, this progress must be sustained for decades to come, and elimination of HBV transmission will require augmented strategies.

Impact of the Ebola outbreak on routine immunization in western area, Sierra Leone - a field survey from an Ebola epidemic area.

BACKGROUND: Since March 2014, the Ebola Virus Disease (EVD) outbreak in West Africa disrupted health care systems - especially in Guinea, Liberia and Sierra Leone - with a consequential stress on the area's routine immunization programs. To address perceived decreased vaccination coverage, Sierra Leone conducted a catch-up vaccination campaign during 24-27 April 2015. We conducted a vaccination coverage survey and report coverage estimates surrounding the time of the EVD outbreak and the catch-up campaign. METHODS: We selected 3 villages from each of 3 communities and obtained dates of birth and dates of vaccination with measles vaccine (MV) and the 3rd dose of Pentavalent vaccine (Pentavalent3) of all children under 4 years of age in the 9 selected villages. Vaccination data were obtained from parent-held health cards. We calculated the children's MV and Pentavalent3 coverage rates at 3 time points, 1 August 2014, 1 April 2015, and 1 May 2015, representing coverage rates before the EVD outbreak, during the EVD outbreak, and after the Maternal and Child Health Week (MCHW) catch-up campaign. RESULTS: The final sample size was 168 children. MV coverage among age-eligible children was 71.3% (95% confidence interval [CI]: 62.1% - 80.4%) and 45.7% (95% CI: 29.2% - 62.2%) before and during the outbreak of EVD, respectively, and was 56.8% (95% CI: 40.8% - 72.7%) after the campaign. Pentavalent3 coverage among age-eligible children was 79.8% (95% CI: 72.6% - 87.0%) and 40.0% (95% CI: 22.5% - 57.5%) before and during the outbreak of EVD, and was 56.4% (95% CI: 39.1% - 73.4%) after the campaign. CONCLUSIONS: Coverage levels of MV and Pentavalent3 were low before the EVD outbreak and decreased further during the outbreak. Although the MCHW catch-up campaign increased coverage levels, coverage remained below pre-outbreak levels. High-quality supplementary immunization activities should be conducted and routine immunization should be strengthened to address gaps in immunity among children in this EVD-affected area.

Population-based surveillance for bacterial meningitis in China, September 2006-December 2009.

During September 2006-December 2009, we conducted active population and sentinel laboratory-based surveillance for bacterial meningitis pathogens, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b, in 4 China prefectures. We identified 7,876 acute meningitis and encephalitis syndrome cases, including 6,388 among prefecture residents. A total of 833 resident cases from sentinel hospitals met the World Health Organization case definition for probable bacterial meningitis; 339 of these cases were among children <5 years of age. Laboratory testing confirmed bacterial meningitis in 74 of 3,391 tested cases. The estimated annual incidence (per 100,000 population) of probable bacterial meningitis ranged from 1.84 to 2.93 for the entire population and from 6.95 to 22.30 for children <5 years old. Active surveillance with laboratory confirmation has provided a population-based estimate of the number of probable bacterial meningitis cases in China, but more complete laboratory testing is needed to better define the epidemiology of the disease in this country.

Prevalence of asymptomatic Bordetella pertussis and Bordetella parapertussis infections among school children in China as determined by pooled real-time PCR: a cross-sectional study.

BACKGROUND: Studies have documented that older children and adolescents act as a reservoir of Bordetella pertussis infection for young infants who have not yet completed their primary immunization schedule. Asymptomatic pertussis infection has been reported during outbreaks. This cross-sectional study aimed to investigate whether B. pertussis and Bordetella parapertussis can colonize the nasopharynx of healthy school children, using culture and pooled real-time PCR with targets for insertion sequences IS481 and IS1001. METHODS: Nasopharyngeal (NP) swabs were taken from 629 asymptomatic school children aged 7 to 15 y in 4 counties of China during the period July-September 2011. The number of subjects included in each county ranged from 153 to 165. The 4 counties selected are located in the north, south, east, and southwest regions of China. NP swabs were inoculated onto Regan-Lowe agar for isolation of suspected Bordetella organisms. Pooled real-time PCRs were used to detect B. pertussis and B. parapertussis based on the IS481 and IS1001 targets separately. RESULTS: Of the 629 subjects, 2 (0.3%) and 30 (4.8%) were confirmed to be culture-positive and PCR-positive, respectively, for B. pertussis, and 1 (0.2%) and 13 (2.1%) were confirmed to be culture-positive and PCR-positive, respectively, for B. parapertussis. All culture-positive samples were also PCR-positive. Furthermore, positive B. pertussis and B. parapertussis samples were found in all counties. CONCLUSIONS: Our results indicate that asymptomatic B. pertussis infections are common in school children in China, and asymptomatic B. parapertussis infections are more prevalent than previously documented.

Comparison of Statistical Signal Detection Methods in Adverse Events Following Immunization - China, 2011-2015.

Introduction: The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization (AEFI) using routinely obtained data in China. Four different methods for detecting vaccine safety signals were evaluated. Methods: The AEFI data from 2011 to 2015 was collected for our study. We analyzed the data using four different methods to detect signals: the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Each method was evaluated at 1-3 thresholds for positivity. To assess the performance of these methods, we used the published signal rates as gold standards to determine the sensitivity and specificity. Results: The number of identified signals varied from 602 for PRR1 (with a threshold of 1) to 127 for MGPS1. When considering the common reactions as the reference standard, the sensitivity ranged from 0.9% for MGPS1/2 to 38.2% for PRR1/2, and the specificity ranged from 85.2% for PRR1 and ROR1 to 96.7% for MGPS1. When considering the rare reactions as the reference standard, PRR1, PRR2, ROR1, ROR2, and BCPNN exhibited the highest sensitivity (73.3%), while MGPS1 exhibited the highest specificity (96.9%). Discussion: For common reactions, the sensitivities were modest and the specificities were high. For rare reactions, both the sensitivities and specificities were high. Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.