Hib结合疫苗的安全性观察

目的了解b型流感嗜血杆菌结合疫苗(Hib)的安全性,为推广使用提供依据。方法采用随机、盲态、同类制品平行对照的Ⅲ期临床试验方法,分6～12月龄、1～5岁2个年龄组,各选取900名婴幼儿,以2∶1的比例,按免疫程序分别接种受试疫苗和对照疫苗,并对接种后AEFI发生情况进行比较。结果接种受试Hib结合疫苗后,AEFI发生率为18.44%;局部、全身反应率均较低,以弱反应为主;2种疫苗间AEFI发生率差异无统计学意义(P均>0.05)。结论 2种疫苗接种后均有良好的安全性。     

b型流感嗜血杆菌疫苗流行病学保护效果Meta分析

目的 评价b型流感嗜血杆菌疫苗(Hib)流行病学保护效果.方法 电子检索National Centerfor Biotechnology Information(NCBI,美国国家医学图书馆数据库)和Cochrane协作网图书馆等数据库,将有关接种Hib流行病学保护效果的研究纳入分析.使用RevMan5.1软件进行统计分析.结果 共纳入7篇文献,均为随机对照试验.Hib 对流感嗜血杆菌侵袭性疾病(Hib-D)保护效果(vE)为88％(95％CI:80％ ～93％),对流感嗜血杆菌脑膜炎(HIB-M)的VE为84％(95％CI:74％～93％).结论 接种Hib可以降低因Hib感染所致侵袭性疾病和脑膜炎的发病率,具有良好的保护效果.     

Haemophilus influenzae meningitis 5 years after introduction of the Haemophilus influenzae type b conjugate vaccine in Brazil

The long-term impact of Haemophilus influenzae type b (Hib) conjugate vaccine, introduced throughout Latin America in the late 1990s, has not been evaluated. Active surveillance for H. influenzae meningitis was performed from August 9, 1996 to August 8, 2004 in Metropolitan Salvador, Brazil. Five years after the introduction of Hib conjugate vaccine, Hib meningitis incidence decreased from 2.39 to 0.06 cases per 100,000 population (98%) overall, and from 60.9 to 3.1 cases per 100,000 population (95%) in children <1 year of age. A transient serotype replacement phenomenon was observed associated with a small increase of meningitis due to two H. influenzae type a clonal groups. These findings indicate that Hib immunization campaign has led to the virtual elimination of Hib disease in this region.     

Bacterial meningitis and Haemophilus influenzae type b conjugate vaccine, Malawi

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997-2009), and pneumococcus was the most common etiologic agent (57% in 2009).     

Haemophilus influenzae type b conjugate vaccine impact against purulent meningitis in Rwanda

Rwanda introduced Haemophilus influenzae type b (Hib) conjugate vaccine in January 2002 and simultaneously implemented pediatric bacterial meningitis surveillance at a major referral hospital in the capital Kigali. We reviewed clinical and laboratory information collected during January 2002 to June 2006. Due to a variety of laboratory limitations, only eight confirmed Hib cases were identified, all before 2004. However, the proportion of cerebrospinal fluid with purulence decreased from 26.0% during 2002, to 15.9% during 2003, 9.7% during 2004 and 8.4% in 2005 (p<0.001). Vaccine effectiveness of two or three doses of Hib vaccine against purulent meningitis was 52% (95% confidence interval, 5-75%). In an African setting with few resources and in which few confirmed Hib meningitis cases were identified, Hib vaccine impact nevertheless could be demonstrated against the outcome of purulent meningitis and was found to be high.     

Impact of routine vaccination with a conjugate Haemophilus influenzae type b vaccine

Based on a unique nationwide registration of vaccinated children, we studied the impact of routine Hib vaccination with special emphasis on vaccine uptake and adherence, vaccine effectiveness with respect to Hib meningitis, and indirect effects with respect to Hib meningitis among the unvaccinated children. Uptake and adherence was generally satisfactory. We estimated >97% effectiveness for all three doses of vaccine and observed herd-immunity in unvaccinated children comparable to a vaccine effectiveness of 94% 3.5 years into the programme. In conclusion, nationwide routine Hib vaccination is highly effective in protecting against Hib meningitis, and rapid achievement of herd immunity is possible with catch-up vaccination of older children.     

Haemophilus influenzae type b vaccines.

Haemophilus influenzae type b (Hib) is a major cause of serious infections in childhood. New vaccines have been developed which are effective in invoking immunity against this organism when administered to children of all ages, including young infants. Their widespread introduction in the UK should lead to a dramatic decline in the incidence of Hib disease.     

Vaccination with Haemophilus influenzae type b conjugate vaccine reduces bacterial meningitis in Morocco

Introduction

Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia and can be prevented by Hib vaccine. We conducted a vaccine impact evaluation to support continued use of Hib vaccine in Morocco following introduction in 2007.

Methods

Bacterial meningitis surveillance data from 2004 to 2009 were obtained from 11 sentinel hospitals located in eight provinces and one prefecture in Morocco to examine Hi meningitis reporting for cases aged <5 years. We defined the years of 2004–2006 as the pre-vaccine period and 2008–2009 as the post-vaccine period and compared the mean annual number of confirmed Hi meningitis cases for these time periods using a Chi-square test. We calculated the minimum incidence of Hi meningitis during the evaluation period in Grand Casa Prefecture, where the catchment population could be estimated.

Results

From 2004 to 2009, 1844 suspected meningitis case-patients aged <5 years were reported; 354 (19.2%) were confirmed with bacterial meningitis, including 105 (29.7%) Hi cases. The mean annual number of confirmed Hi meningitis cases decreased by 75%, from 24 in the pre-vaccine period to 6 during the post-vaccine period (p < 0.001). Assuming Hi cases with unknown age were <5 years of age, the estimated minimum incidence of confirmed Hi meningitis in Grand Casa Prefecture decreased by 93%, from 15 cases per 100,000 children in the pre-vaccine period to 1 case per 100,000 children in the post-vaccine period.

Conclusion

Hib vaccine introduction likely significantly reduced the occurrence of Hi meningitis among children aged <5 years at the 11 sentinel hospitals included in this evaluation in Morocco, suggesting that continued use of Hib vaccine in Morocco would be beneficial.     

Long-term persistence of immunity after immunisation with Haemophilus influenzae type b conjugate vaccine

Although Haemophilus influenzae type b (Hib) conjugate vaccines, after licensure in 1987, are now recommended for world-wide use, the duration of protective immunity afforded by them is not known. We therefore assessed the immunogenity at 9-10 years of age in 37 children who had received the first Hib conjugate, PRP-D, in infancy (the Hib-conjugate group) and were now given a dose of Hib polysaccharide (PS) as a test vaccine. The anti-Hib PS antibodies (Hib-ab) were measured before and after this test vaccination, and the values compared to those in 37 control children who had not previously received any Hib vaccine and in 13 children who had received Hib PS vaccine in infancy (the Hib-PS group). Prior to the test vaccination, the Hib-ab concentrations in the Hib-conjugate group were 3.6-fold higher than in the control group. After the test vaccination, the Hib-conjugate group had higher total Hib-ab concentrations, higher proportion of IgG and higher avidity of Hib-ab than the control or the Hib-PS group, suggesting persisting immunological memory in a Hib-c group. A mathematical model, including memory, predicted accurately the Hib-ab concentrations, which are maintained through anamnestic responses to intervening stimuli (Hib or cross-reacting bacteria).     

关注我国儿童b型流感嗜血杆菌疾病及其疫苗的使用

b型流感嗜血杆菌（Hib）是全世界儿童发病和死亡的主要原因之一，引起儿童严重感染（脑膜炎、败血症和肺炎）。据估计，全球每年有38万～50万儿童死于Hib感染的疾病，并导致儿童死亡与残疾。Hib结合疫苗的问世，大大减少了发达国家的Hib疾病的发病率，1990年前后美国、芬兰和瑞典等国使用这种疫苗，Hib发病率降低95％以上。这种疫苗安全可靠，副反应小，免疫效果好，     

A nationwide population-based surveillance of invasive Haemophilus influenzae diseases in children after the introduction of the Haemophilus influenzae type b vaccine in Japan

BackgroundHaemophilus influenzae type b (Hib) vaccine was introduced as a voluntary vaccine in December 2008 and was included in the national routine immunization program in April 2013 in Japan. Currently, no nationwide data are available to evaluate the effectiveness of Hib vaccine in Japan.MethodsTo evaluate the effectiveness of Hib vaccine in Japan, nationwide active population-based surveillance of culture-proven invasive infections caused by H. influenzae in children was performed in 2008–2017 in 10 prefectures in Japan (covering approximately 23% of the total Japanese population). Clinical data were recorded on a standardized case report form. Capsular type and antimicrobial susceptibility of the H. influenzae isolates were examined. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare data from 5 years before and that from after the introduction of the national routine Hib vaccine immunization program.ResultsDuring the 10-year study period, 566 invasive H. influenzae disease cases including 336 meningitis cases were identified. The average number of invasive H. influenzae disease cases among children <5 years of age during 2013–2017 decreased by 93% (IRR: 0.07, 95%CI 0.05–0.10, p < 0.001) compared with those occurring during 2008–2012. Hib strains have not been isolated from invasive H. influenzae disease cases since 2014; however, non-typeable H. influenzae and H. influenzae type f isolates have been noted as causes of invasive H. influenzae diseases among children <5 years in the post-Hib vaccine era.ConclusionsAfter the governmental subsidization of the Hib vaccine, invasive Hib disease cases decreased dramatically in the study population, as per our surveillance. Continuous surveillance is necessary to monitor the effectiveness of Hib vaccine and for detecting any emerging invasive capsular types.     

Economic evaluation of delivering Haemophilus influenzae type b vaccine in routine immunization services in Kenya

OBJECTIVE: Haemophilus influenzae type b (Hib) vaccine was introduced into routine immunization services in Kenya in 2001. We aimed to estimate the cost-effectiveness of Hib vaccine delivery. METHODS: A model was developed to follow the Kenyan 2004 birth cohort until death, with and without Hib vaccine. Incidence of invasive Hib disease was estimated at Kilifi District Hospital and in the surrounding demographic surveillance system in coastal Kenya. National Hib disease incidence was estimated by adjusting incidence observed by passive hospital surveillance using assumptions about access to care. Case fatality rates were also assumed dependent on access to care. A price of US$ 3.65 per dose of pentavalent diphtheria-tetanus-pertussis-hep B-Hib vaccine was used. Multivariate Monte Carlo simulations were performed in order to assess the impact on the cost-effectiveness ratios of uncertainty in parameter values. FINDINGS: The introduction of Hib vaccine reduced the estimated incidence of Hib meningitis per 100,000 children aged < 5 years from 71 to 8; of Hib non-meningitic invasive disease from 61 to 7; and of non-bacteraemic Hib pneumonia from 296 to 34. The costs per discounted disability adjusted life year (DALY) and per discounted death averted were US$ 38 (95% confidence interval, CI: 26-63) and US$ 1197 (95% CI: 814-2021) respectively. Most of the uncertainty in the results was due to uncertain access to care parameters. The break-even pentavalent vaccine price--where incremental Hib vaccination costs equal treatment costs averted from Hib disease--was US$ 1.82 per dose. CONCLUSION: Hib vaccine is a highly cost-effective intervention in Kenya. It would be cost-saving if the vaccine price was below half of its present level.     

Mathematical models of Haemophilus influenzae type b.

A review of empirical studies and the development of a simple theoretical framework are used to explore the relationship between Haemophilus influenzae type b (Hib) carriage and disease within populations. The models emphasize the distinction between asymptomatic and symptomatic infection. Maximum likelihood methods are used to estimate parameter values of the models and to evaluate whether models of infection and disease are satisfactory. The low incidence of carriage suggests that persistence of infection is only compatible with the absence of acquired immunity to asymptomatic infection. The slight decline in carriage rates amongst adults is compatible with acquired immunity, but could be a consequence of reduced contacts. The low rate of disease observed in adulthood cannot be explained if protection from disease is a product of previous detectable exposure to Hib alone. We estimate an R0 of 3.3 for Hib in developed countries, which suggests that current immunization programmes may eliminate the infection. Analysis of the disease data set suggests the absence of maternal immunity and increased susceptibility to disease in the oldest age classes.     

Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa

OBJECTIVE: To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS: We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS: The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION: Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection.     

Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs

In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.     

Haemophilus influenzae type b reemergence after combination immunization

An increase in Haemophilus influenzae type b (Hib) in British children has been linked to the widespread use of a diphtheria/tetanus/acellular pertussis combination vaccine (DTaP-Hib). We measured anti-polyribosyl-ribitol phosphate antibody concentration and avidity before and after a Hib booster in 176 children 2-4 years of age who had received 3 doses of DTP-Hib (either DT whole cell pertussis-Hib or DTaP-Hib) combination vaccine in infancy. We also measured pharyngeal carriage of Hib. Antibody concentrations before and avidity indices after vaccination were low (geometric mean concentration 0.46 mug/mL, 95% confidence interval [CI] 0.36-0.58; geometric mean avidity index 0.16, 95% CI 0.14-0.18) and inversely related to the number of previous doses of DTaP-Hib (p = 0.02 and p<0.001, respectively). Hib was found in 2.1% (95% CI 0.7%-6.0%) of study participants. Our data support an association between DTaP-Hib vaccine combinations and clinical Hib disease through an effect on antibody concentration and avidity.