Giant Low-Field Cryogenic Magnetocaloric Effect in a Polycrystalline EuB4O7 Compound.

To deal with the shortage and high price of helium-3 resources, adiabatic demagnetization refrigeration technology as an alternative to helium-3-based refrigeration technology has received much attention. The magnetism and ultralow-temperature magnetocaloric effect (MCE) of the EuB4O7 compound have been investigated. The results of magnetic and quasi-adiabatic demagnetization measurements suggest the absence of a magnetic order above 0.4 K for EuB4O7. The dipolar interaction between the nearest-neighbor Eu atoms has a characteristic energy of about 800 mK, which may induce a large MCE. The maximum magnetic entropy change reaches 22.8, 36.2, and 47.6 J·kg-1 K-1 at µ0H = 0-10 kOe, 0-20 kOe, and 0-50 kOe, respectively. Measurements by a quasi-adiabatic demagnetization device show that the lowest temperature achievable (289 mK) for polycrystalline EuB4O7 is lower than that (362 mK) for the commercial refrigerant Gd3Ga5O12 (GGG) single crystals. The hold time is more than 70 min below 700 mK, with an environment temperature of 2 K, proving that EuB4O7 exhibits superior cooling performance.

An inactivated enterovirus 71 vaccine in healthy children.

BACKGROUND: Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71. RESULTS: A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo. CONCLUSIONS: The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).

Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

BACKGROUND: The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. METHODS: In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. RESULTS: Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. CONCLUSIONS: The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV.

Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations.

BACKGROUND: To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy. METHODS: A sub-cohort of 1,100 volunteers from Guangxi Province in China was eligible for enrolment and randomly administered either the EV71 vaccine or a placebo on days 0 and 28 in a phase III clinical trial and then observed for the following 2 years with approval by an independent ethics committee of Guangxi Zhuang Autonomous Region, China. Serum samples from the 350 participants who provided a full series of blood samples (at all the sampling points) within the 2-year period were collected. Vaccine-induced immune effects, including the neutralizing antibody titres and cross-protection against different genotypes of EV71, were examined. This study also evaluated the protective efficacy of this vaccine based upon clinical diagnosis. RESULTS: This sub-cohort showed a >60% drop-out rate over 2 years. The seroconversion rates among the 161 immunized subjects remained >95% at the end of study. The geometric mean titres of neutralizing antibodies (anti-genotype C4) 360 days after vaccination in 350 subjects were 81.0 (subjects aged 6-11 months), 98.4 (12-23 months), 95.0 (24-35 months), and 81.8 (36-71 months). These titres subsequently increased to 423.1, 659.0, 545.0, and 321.9, respectively, at 540 days post-immunization (d.p.i.), and similar levels were maintained at 720 d.p.i. Higher IFN-γ/IL-4-specific responses to the C4 genotype of EV71 and cross-neutralization reactivity against major EV71 genotype strains were observed in the vaccine group compared to those in the placebo group. Five EV71-infected subjects were observed in the placebo-treated control group and none in the vaccine-immunized group in per-protocol analysis. CONCLUSION: These results are consistent with the induction of dynamic immune responses and protective efficacy of the vaccine against most circulating EV71 strains. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT01569581, Trial registration date: March 2012.

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Porous boron nitride with a high surface area: hydrogen storage and water treatment.

We report on the synthesis of high-quality microporous/mesoporous BN material via a facile two-step approach. An extremely high surface area of 1687 m(2) g(-1) and a large pore volume of 0.99 cm(3) g(-1) have been observed in the synthesized BN porous whiskers. The formation of the porous structure was attributed to the group elimination of organic species in a BN precursor, melamine diborate molecular crystal. This elimination method maintained the ordered pore structure and numerous structural defects. The features including high surface area, pore volume and structural defects make the BN whiskers highly suitable for hydrogen storage and wastewater treatment applications. We demonstrate excellent hydrogen uptake capacity of the BN whiskers with high weight adsorption up to 5.6% at room temperature and at the relatively low pressure of 3 MPa. Furthermore, the BN whiskers also exhibit excellent adsorption capacity of methyl orange and copper ions, with the maximum removal capacity of 298.3 and 373 mg g(-1) at 298 K, respectively.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Safety and immunogenicity of a skin- and neuro-attenuated live vaccine for varicella: a randomized, double-blind, controlled, dose-escalation and age de-escalation phase 1 clinical trial.

Background: Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D). Methods: This is a randomized, double-blind, placebo-controlled, dose-escalation and age de-escalation phase 1 clinical trial conducted in Liuzhou, China (ChiCTR1900022284). Eligible healthy participants aged 1-49 years, with no history of varicella vaccination and had no history of varicella or herpes zoster were sequentially enrolled and allocated to subcutaneously receive one of the three doses (3.3, 3.9, and 4.2 lg PFU) of v7D, vOka or placebo in a dose-escalation and age de-escalation manner. The primary outcome was safety, assessed by adverse events/reactions within 42 days after vaccination and serious adverse events (SAEs) throughout six months after vaccination. The secondary outcome was immunogenicity, assessed by the VZV IgG antibodies measured with fluorescent antibody to membrane antigen (FAMA) assay. Findings: Between April 2019 and March 2020, totally 224 participants were enrolled. Within 42 days post-vaccination, the incidences of adverse reactions were 37.5%-38.7% in the three doses of v7D groups which were similar to that of the vOka (37.5%) and placebo (34.4%) groups. No SAE has been judged as causally related to vaccination. At 42 days post-vaccination, 100% of children aged 1-12 years in the per-protocol set of immunogenicity cohort of the v7D groups became seropositive. Meanwhile, in the intent-to-treat set of immunogenicity cohort of subjects aged 1-49 years, the geometric mean increases of the three groups of v7D vaccine were 3.8, 5.8 and 3.2, respectively, which were similar to that of the vOka vaccine group (4.4) and significantly higher than that of the placebo group (1.3). Interpretation: The candidate v7D vaccine has been preliminarily shown to be well-tolerated and immunogenic in humans. The data warrant further evaluation of the safety advantage and efficacy of v7D as a varicella vaccine. Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai CO., LTD.

A phase II, single-center, randomized, double-blind, parallel control clinical study evaluating the immunogenicity and safety of a two-dose schedule of serogroups ACYW meningococcal polysaccharide conjugate vaccine.

BACKGROUND: This was a single-center, randomized, double-blind, parallel control study evaluating the immunogenicity and safety of a two-dose schedule of serogroups ACYW meningococcal polysaccharide conjugate vaccine with tetanus toxoid (TT) conjugate protein, in infants and toddlers of 3-35 months old. METHOD: 720 participants were stratified according to the age of 3-5 months old, 6-11 months old, and 12-35 months old and randomly assigned with an equal ratio to two different dose groups, i.e., 40- and 20-µg doses. Blood samples were taken from all participants before the first vaccination and 30 days after the full-course vaccination to detect the serogroups ACYW meningococcal antibodies. All adverse events occurred within 30 days after vaccination of each dose, and serious adverse events occurred within six months after full-course vaccination were collected for safety evaluation. This study was registered at the China drug trial registration with the identifier CTR 20182031. RESULTS: After 30 days of full-course vaccination, 92.78 % (95 % CI: 85.70 %-100.00 %) showed the immune response against all serogroups in both high-dose and low-dose groups by rabbit serum bactericidal antibody assay (rSBA) and the geometric mean titer (GMT) of all serogroups showed a high level (74.6-505.8, 95 % CI: 56.4-615.7). However, no significant difference between different dose groups was observed (P > 0.05). The common local and systemic adverse events in both groups were redness (3 %-7%), and fever (26 %-65 %), respectively. In addition, the grade 3 adverse event related to the vaccine was fever (1.67 %-12.50 %). No serious adverse event was reported to be associate with the vaccination. CONCLUSION: The serogroups ACYW meningococcal polysaccharide conjugate vaccine was safe and effective in the population aged 3-35 months. The vaccine efficacy and safety of the 20-µg dose group were not less than that of the 40-µg dose group.

Safety and immunogenicity of an Escherichia coli-produced bivalent human papillomavirus type 6/11 vaccine: A dose-escalation, randomized, double-blind, placebo-controlled phase 1 trial.

A dose-escalation, randomized, double-blind, placebo-controlled phase 1 clinical trial enrolled 145 eligible participants aged 18-55 years in March 2015 in Liuzhou, China. Stratified by age and sex, the participants were randomly assigned to receive either 30, 60, or 90 µg of the HPV-6/11 vaccine (n = 41/40/40) or the parallel placebo vaccine (n = 8/8/8) with a 0/1/6-month dose-escalation schedule. Participants were actively followed-up to record local and systemic AEs occurring within 30 days after each vaccination, and SAEs occurred in 7 months. Blood and urine samples of each participant were collected before and 2 days after the first and third vaccination to determine changes in routine blood, serum biochemical, and urine indexes. Serum HPV-6/11-specific IgG and neutralizing antibody levels at month 7 were analyzed. A total of 79 adverse events were reported, and no SAEs occurred. The incidences of total adverse reactions in the 30 µg, 60 µg, and 90 µg HPV vaccine groups and the control group were 31.7%, 50.0%, 42.5%, and 62.5%, respectively. All but one of the adverse reactions was mild or moderate with grade 1 or 2. No vaccine-related changes with clinical significance were found in paired blood and urine indexes before and after vaccinations. All the participants in the per-protocol set seroconverted at month 7 for both IgG and neutralizing antibodies. The candidate novel Escherichia-coli-produced bivalent HPV-6/11 vaccine has been preliminarily proven to be well tolerated and with robust immunogenicity in a phase 1 clinical study, supporting further trials with larger sample size. The study has been registered at ClinicalTrials.gov (NCT02405520).

Efficacy, safety and immunogenicity of hexavalent rotavirus vaccine in Chinese infants.

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n â€‹= â€‹3200) or placebo (n â€‹= â€‹3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.

Giant and reversible low field magnetocaloric effect in LiHoF4 compound.

Cryogenic refrigeration technology is gradually penetrating into increasing aspects of human life and industrial production. Magnetic refrigeration shows excellent application potential due to its high efficiency, good stability and environmental friendliness. It is important for a magnetic refrigeration system to secure a high-performance magnetocaloric material under a low applied magnetic field, which can greatly simplify the design and reduce the expense. In this study, LiHoF4, a polycrystalline compound prepared by an improved solid-state reaction method undergoes a second-order phase transition below 2 K. Meanwhile, an unexpected giant low-field magnetocaloric effect has been observed. The maximum magnetic entropy changes are 11.0 J kg-1 K-1, 19.0 J kg-1 K-1, and 25.9 J kg-1 K-1 in field changes of 0.6 T, 1.0 T, and 2.0 T, respectively. The giant and reversible low field magnetocaloric effect proves it to be one of the most practical candidates among the cryogenic magnetic refrigerants.

Heteroatom coordination induces electric field polarization of single Pt sites to promote hydrogen evolution activity.

Herein, we reported a kind of single Pt site (Pt-SA) stabilized on an MXene support (Pt-SA/MXene) via the formation of Pt-O and Pt-Ti bonds to effectively catalyze the hydrogen evolution reaction (HER). Due to the local electric field polarization derived from its unique asymmetric coordination, Pt-SA/MXene displays remarkably higher catalytic HER activity in an alkaline electrolyte. In detail, the Pt-SA/MXene electrocatalyst only needs a low overpotential of 33 mV to reach a current density of 10 mA cm-2 and maintains the performance over 27 h. Besides, Pt-SA/MXene also has a competitive mass activity, 23.5 A mgPt-1, at an overpotential of 100 mV, which is 29.4 times greater than that of the commercial Pt/C counterpart. Density functional theory (DFT) calculations revealed that the polarized electric field could efficiently tailor the electronic structure of Pt-SA/MXene and reduce the energy barrier of adsorption/desorption of the H* intermediate step, further improving its HER catalytic activity.

Safety and Immunogenicity of a Shigella Bivalent Conjugate Vaccine (ZF0901) in 3-Month- to 5-Year-Old Children in China.

No licensed Shigella vaccine is presently available globally. A double-blinded, randomized, placebo-controlled, age descending phase II clinical trial of a bivalent conjugate vaccine was studied in China. The vaccine ZF0901 consisted of O-specific polysaccharides purified and detoxified from lipopolysaccharide (LPS) of S. flexneri 2a and S. sonnei and covalently bonded to tetanus toxoid. A total of 224, 310, and 434 children, consented by parents or guardians, aged 3 to 6 and 6 to 12 months and 1 to 5 years old, respectively, were injected with half or full doses, with or without adjuvant or control Hib vaccine. There were no serious adverse reactions in all recipients of ZF0901 vaccine independent of age, dosage, number of injections, or the adjuvant status. Thirty days after the last injection, ZF0901 induced robust immune responses with significantly higher levels of type-specific serum antibodies (geometric mean concentrations (GMCs) of IgG anti-LPS) against both serotypes in all age groups compared with the pre-immune or the Hib control (p < 0.0001). Here, we demonstrated that ZF0901 bivalent Shigella conjugate vaccine is safe and immunogenic in infants and young children and is likely suitable for routine immunization.

Burden and etiology of moderate and severe diarrhea in children less than 5 years of age living in north and south of China: Prospective, population-based surveillance.

BACKGROUND: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. METHODS: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. RESULTS: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. CONCLUSION: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus.

Post hoc analysis of two clinical trials to compare the immunogenicity and safety of different polio immunization schedules in Chinese infants.

BACKGROUND: A comparative analysis of the immunogenicity and safety of different poliovirus immunization schedules in Chinese infants is imperative to guide the administration of efficient strategies for the eradication of poliomyelitis. METHODS: A post hoc analysis was conducted with the data from two poliovirus vaccine clinical trials involving a combined total of 2,400 infants aged 60-90 days. Trivalent oral poliovirus vaccine (tOPV), bivalent oral poliovirus vaccine (bOPV), Sabin strain-based inactivated poliovirus vaccine (sIPV), and conventional inactivated poliovirus vaccine (cIPV) were used in different schedules, the immunogenicity and safety of which were compared 28 days after the last of three doses. RESULTS: In a per-protocol set analysis, the tOPV-tOPV-tOPV schedule induced seroconversion in 99.1%, 98.2%, and 96.0% of the inoculated infants for poliovirus type I, II, and III, respectively. The seroconversions for poliovirus types I and III were each almost 100% after immunization with the cIPV-bOPV-bOPV, sIPV-sIPV-bOPV, cIPV-cIPV-bOPV, sIPV-sIPV-tOPV, cIPV-cIPV-tOPV, or sIPV-bOPV-bOPV schedule. However, the schedules that used one IPV dose followed by two (poliovirus type I and III) bOPV doses failed to induce high-level immunity against type II poliovirus. IPV-related schedules were associated with a slightly higher incidence of adverse events (AEs). CONCLUSIONS: If the capacity of IPV can be increased, two or more doses of IPV should be administered before vaccination with bOPV in a sequential schedule to improve immunity against type II poliovirus.

Burden of viral gastroenteritis in children living in rural China: Population-based surveillance.

BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China.

Epidemiological investigations of human rabies in China.

BACKGROUND: The epidemic of rabies showed a rising trend in China in recent years. To identify the potential factors involved in the emergence, we investigated and analyzed the status and characteristics of human rabies between 1996 and 2008. Moreover, the status of rabies infection and vaccination in dogs, and prophylaxis of humans after rabies exposure were analyzed. METHODS: Human rabies data in China between 1996 and 2008 collected from the annual reports of Chinese Center for Disease Control and Prevention (China CDC) were analyzed. To investigate the status of dogs and postexposure prophylaxis (PEP) of humans, brain specimens of domestic dogs were collected and detected, and the demographic details, exposure status and PEP of rabies patients were obtained in 2005 and 2006 in Guangxi, Hunan and Guizhou provinces. RESULTS: The results showed 19,806 human rabies cases were reported in China from 1996 to 2008, with an average of 1,524 cases each year, and the incidence almost was rising rapidly, with the peak in 2007 (3,300 cases). It was notable that nearly 50% of the total rabies cases nationwide were reported in Guangxi, Hunan and Guizhou provinces. In these three provinces, the rabies infection rate in dogs was 2.3%, and 60% investigated cities had a dog vaccination rate of below 70%; among the 315 recorded human cases, 66.3% did not receive any PEP at all, 27.6% received inadequate PEP, and only 6.0% received a full regime of PEP. CONCLUSIONS: In recent years, rabies is reemerging and becoming a major public-health problem in China. Our analysis showed that unsuccessful control of dog rabies and inadequate PEP of patients were the main factors leading to the high incidence of human rabies in China, then there are following suggestions: (1) Strict control of free-ranging dogs and mandatory rabies vaccination should be enforced. (2)Establishing national animal rabies surveillance network is imperative. (3) PEP should be decided to initiate or withhold according to postmortem diagnosis of the biting animal. (4) The cost of PEP should be decreased or free, especially in rural areas. (5)Education of the public and health care staff should be enhanced.

Immunogenicity of pentavalent rotavirus vaccine in Chinese infants.

BACKGROUND: A phase III, randomized, double-blind, placebo-controlled clinical study was conducted in China to assess the efficacy, safety, and immunogenicity of the pentavalent rotavirus vaccine (RotaTeqTM, RV5) among Chinese infants. The efficacy and safety data have been previously reported. This report presents the immunogenicity data of the study. METHODS: 4,040 infants aged 6-12 weeks were randomly assigned in a 1:1 ratio to receive 3 oral doses of RV5 or placebo. Trivalent oral poliovirus vaccine (tOPV) and diphtheria, tetanus, and acellular pertussis vaccine (DTaP) were administered in a staggered-use (N = 3,240) or concomitant-use (N = 800) schedule. Immunogenicity of RV5 was evaluated in 800 participants (400 participants from each staggered- and concomitant-use immunogenicity subgroup). Geometric mean titers (GMTs) and seroresponse rates (≥3-fold rise from baseline to PD3) were measured for anti-rotavirus IgA in the staggered- and concomitant-use subgroups and measured for serum neutralizing antibodies (SNAs) to human rotavirus serotypes G1, G2, G3, G4, P1A[8] in the staggered-use subgroup. Immune responses to tOPV and DTaP co-administered with RV5 were also evaluated in the concomitant-use immunogenicity subgroup. (ClinicalTrials.gov registry: NCT02062385) RESULTS: The PD3 GMT and seroresponse rate of anti-rotavirus IgA were higher in the RV5 group (82.42 units/mL, 89.4%) compared to the placebo group (0.33 units/mL, 10.1%). Rotavirus type-specific SNA responses were also higher in the RV5 group compared to the placebo group. In the concomitant-use subgroup, the seroprotection rates of anti-poliovirus type 1, 2, 3 in the participants who received RV5 were non-inferior to those who received placebo, and the antibody responses to DTaP antigens were comparable between the two vaccination groups. CONCLUSIONS: RV5 was immunogenic in Chinese infants. Immune responses induced by tOPV and DTaP were not affected by the concomitant use of RV5.

Immunological Effect of aGV Rabies Vaccine Administered Using the Essen and Zagreb Regimens: A Double-Blind, Randomized Clinical Trial.

This study evaluated the immunological effect of an aGV rabies virus strain using the Essen and Zagreb immunization programs. A total of 1,944 subjects were enrolled and divided into three groups: the Essen test group, Essen control group, and Zagreb test group. Neutralizing antibody levels and antibody seroconversion rates were determined at 7 and 14 days after the initial inoculations and then 14 days after the final inoculation in all of the subjects. The seroconversion rates for the Essen test group, Essen control group, and Zagreb test group, which were assessed 7 days after the first dosing in a susceptible population, were 35.74%, 26.92%, and 45.49%, respectively, and at 14 days, the seroconversion rates in this population were 100%, 100%, and 99.63%, respectively. At 14 days after the final dosing, the seroconversion rates were 100% in all three of the groups. The neutralizing serum antibody levels of the Essen test group, Essen control group, and Zagreb test group at 7 days after the first dosing in the susceptible population were 0.37, 0.26, and 0.56 IU/mL, respectively, and at 14 days after the initial dosing, these levels were 16.71, 13.85, and 16.80 IU/mL. At 14 days after the final dosing, the neutralizing antibody levels were 22.9, 16.3, and 18.62 IU/mL, respectively. The results of this study suggested that the aGV rabies vaccine using the Essen program resulted in a good serum immune response, and the seroconversion rates and the neutralizing antibody levels generated with the Zagreb regimen were higher than those with the Essen regimen when measured 7 days after the first dose.