Safety of influenza A (H1N1) vaccine in postmarketing surveillance in China.

BACKGROUND: On September 21, 2009, China began administering vaccines, obtained from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program. METHODS: We designed a plan for passive surveillance for adverse events after immunization with the influenza A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention (CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System's National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC. RESULTS: A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain-Barré syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China. CONCLUSIONS: No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain-Barré syndrome.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Effect of aluminum hydroxide adjuvant on the immunogenicity of the 2009 pandemic influenza A/H1N1 vaccine: multi-level modeling of data with repeated measures.

OBJECTIVE: To evaluate the effect of the aluminum hydroxide (Al-OH) adjuvant on the 2009 pandemic influenza A/H1N1 (pH1N1) vaccine. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 µg hemagglutinin antigen, with or without aluminum hydroxide (Al-OH). We classified the participants into six age categories (>61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years) and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer (GMT) of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. RESULTS: The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. CONCLUSION: The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

Inhibitory effects of sulfamethoxazole on denitrifying granule properties: Short- and long-term tests.

The broad-spectrum antibiotic sulfamethoxazole (SMX) was chosen to assess its short- and long-term effects on denitrifying granules. The SMX concentration and pre-exposure time in batch testing influenced the denitrifying granule activity. In the continuous-flow experiments, no inhibitory effects on the upflow anaerobic sludge blanket performance were observed at SMX concentrations up to 100mgL-1, probably because of functional redundancy and long-term acclimation. The specific denitrifying activity first decreased to a minimum of 49.3% and then recovered to a level comparable to the initial level as the SMX concentration increased. The changing trend of the extracellular polymer content was consistent with the specific denitrifying activity throughout the process, and relatively high EPS loss ratios (maximum loss of 61.8%) were observed. Additionally, the diameter of the denitrifying granules monophonically increased to a final value of 35.0%. This research provided the application of denitrifying granules to treat wastewater that contained antibiotic.

[Review of the sudden death and death following immunization of influenza vaccine].

To evaluate the safety of influenza Type A (H1N1) vaccine by review the incidence, epidemiology characteristics of sudden death and the deaths related with immunization, especially focus on the sudden deaths after immunization of influenza Type A (H1N1) vaccine. Preliminary showed that those deaths reported as adverse events following immunization did not associated with the vaccine. Vaccination campaign according to the national immunization strategy should be carried out and appropriately respond to the emergency events should be strenghtened.

[Study on the estimation of routine immunization coverage of China, 2005-2007].

OBJECTIVE: This study is to estimate the routine immunization coverage of China, and to analyse the effect factors. METHODS: The reported routine coverage data in 2005-2007 were collected through China Immunization information system. The estimated coverage method used in this study, which was recommended by the World Health Organization (WHO). RESULTS: The percentage of county reported routine immunization were 79.8%, 92.3% and 92.0% respectively in 2005-2007; the targeted population of routine immunization reported from China immunization information system were 123-140.6 million, the vaccinated population were between 91.3-139.5 million; reported routine immunization coverage of each vaccine dose varied from 89%-100%, and estimated coverage varied from 78%-94%. CONCLUSION: The reported and estimated routine immunization coverage increased year by year. However, there is still a large gap between the reported data and the estimated data. It is recognized that the birth cohort and the adjusted index from the WHO recommended method should be used carefully.

[Literature review of adverse events following immunization of Bacillus Calemtte-Guerin vaccine].

OBJECTIVE: This article is to analyze the features of adverse events following immunization (AEFI) in BCG Literatures, and to provide information for AEFI surveillance and diagnosis. METHODS: The literatures were collected from CHKD and WANFANG databases, then the information from qualified publications were analysed. RESULTS: 100 cases from 90 publications were involved. >10 literatures were published every year in 2000-2007. 65% cases occurred < or =1 day and > or =15 days after vaccination. 54% cases occurred in the first dose. 21 cases were local redness and swelling, 16 cases were local indurations. 15 cases were suppurative lymphadenitis. 66% cases were cured. Of 100 cases, 40 were program error events, 40 cases were rare, serious vaccine reactions and 18 were coincidental illnesses. In all practice error events, 28 were using BCG as other vaccines and 12 were vaccination error. 71 of 100 cases were diagnosed by author, 17 by hospital, 9 by CDC and 3 by the expert group for AEFI diagnosis. CONCLUSIONS: Overall, the mainly reason of BCG AEFI was operational error event. The serious cases, such as death, were related to immunological deficiency. The training of vaccination conductors and the clinical physicians should be strengthened in order to standardize the vaccination. The standardized immunization services and diagnosis of AEFI will reduce AEFI occurrence and the disputations about AEFI.

[Literature review on adverse events following immunization for influenza virus vaccine].

To evaluate security of influenza virus vaccines by analysis of adverse reaction to influenza virus vaccine, especially the relationship between Guillain Barré syndrome and influenza vaccines.

[Analysis on the surveillance of adverse events following immunization in China, 2007-2008].

OBJECTIVE: The study is to analyze the occurrence features of Adverse Event Following Immunization (AEFI) in China, and to evaluate the implementation of AEFI surveillance system, the safety of National Immunization Program (NIP) Vaccines and the quality of the immunization services. METHODS: The AEFI data of 2007-2008 were collected through the China Information System and the Children Immunization Information System, which reported before march 25, 2009. The descriptive methodology was used in the study. RESULTS: 32120 AEFI cases of 2007-2008 were reported, 95.02% were reported from 10 pilot provinces. The ratio of male and female was 1.41:1.77. 53% cases were < OR =1 years old and the cases were occurred more often between april to october. The first three vaccines are DPT, MPV and JREV. 65.85% happened after the 1st and 2nd dose and 75.05% within 1 d after vaccination. The estimat reported incidence of NIP vaccines were 7.99-322.77 per million doses. In the classification of AEFI cases, 79.93% cases were common, minor reactions, 14.65% were rare, serious reactions and others were <5%. Anaphylaxis, sterile abscess and vaccine reaction of BCG were the most common clinical diagnosis. 91.2% AEFI cases were cured or improved. Only 1.93% were hospitalized, among them 2/3 stayed in hospital < or = 10 d. CONCLUSIONS: Comparing with 2005-2006, the completeness and sensitivity of national AEFI surveillance system were improved greatly in 2007-2008, but it still needs to be strengthened. The NIP vaccines were significantly related to the introduced vaccines in Expanded Immunization Program. AEFIs occurrence mostly in young children, first-dose and the early period of vaccination. The pilot study showed that safety of NIP vaccines and the quality of immunization services are satisfied.

[Review on the risk of sequela after serious vaccination reaction].

To evaluate the risk of sequela after serious vaccine reaction. The rare serious vaccine reactions might result in sequela, the incidence of rare serious vaccine reactions, the estimated incidence of sequela and cases reported were reviewed. Further research should be developed to provide the scientific basis for sequela control and prevention.