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.     

Cost-effectiveness of Haemophilus influenzae type b vaccine in Vietnam

BackgroundWith GAVI support, Vietnam introduced Haemophilus influenzae type b (Hib) vaccine in 2010 without evidence on cost-effectiveness. We aimed to analyze the cost-effectiveness of Hib vaccine from societal and governmental perspectives.MethodWe constructed a decision-tree cohort model to estimate the costs and effectiveness of Hib vaccine versus no Hib vaccine for the 2011 birth cohort. The disease burden was estimated from local epidemiologic data and literature. Vaccine delivery costs were calculated from governmental reports and 2013 vaccine prices. A prospective cost-of-illness study was conducted to estimate treatment costs. The human capital approach was employed to estimate productivity loss. The incremental costs of Hib vaccine were divided by cases, deaths, and disability-adjusted life years (DALY) averted. We used the WHO recommended cost-effectiveness thresholds of an intervention being highly cost-effective if incremental costs per DALY were below GDP per capita.ResultFrom the societal perspective, incremental costs per discounted case, death and DALY averted were US$ 6252, US$ 26,476 and US$ 1231, respectively; the break-even vaccine price was US$ 0.69/dose. From the governmental perspective, the results were US$ 6954, US$ 29,449, and US$ 1373, respectively; the break-even vaccine price was US$ 0.48/dose. Vietnam's GDP per capita was US$ 1911 in 2013. In deterministic sensitivity analysis, morbidity and mortality parameters were among the most influential factors. In probabilistic sensitivity analysis, Hib vaccine had an 84% and 78% probability to be highly cost-effective from the societal and governmental perspectives, respectively.ConclusionHib vaccine was highly cost-effective from both societal and governmental perspectives. However, with GAVI support ending in 2016, the government will face a six-fold increase in its vaccine budget at the 2013 vaccine price. The variability of vaccine market prices adds an element of uncertainty. Increased government commitment and improved resource allocation decision making will be necessary to retain Hib vaccine.     

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。     

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.     

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.     

Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children--United States, 1998-2000

Haemophilus influenzae type b (Hib) was the leading cause of bacterial meningitis and a major cause of other serious invasive diseases among children aged <5 years in the United States before Hib conjugate vaccines became available in 1988. In 1991, all infants starting at age 2 months were recommended to receive Hib conjugate vaccines; by 1996, incidence of Hib invasive disease (i.e., illness clinically compatible with invasive disease, such as meningitis or sepsis, with isolation of the bacterium from a normally sterile site) among children aged <5 years had declined by >99%. This report presents 1998-2000 Haemophilus influenzae (Hi) surveillance data, which indicate that the incidence of reported Hib invasive disease remains low. Achieving the national health objective for 2010 of reducing to zero indigenous Hib invasive disease cases in children aged <5 years will require improved age-appropriate vaccination of children, complete reporting of vaccination and relevant medical histories, standardization of the serotyping procedure, and complete ascertainment and reporting of serotype for all Hi invasive disease cases.     

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).     

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.     

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.     

Impact of the introduction of the Haemophilus influenzae type b conjugate vaccine in an urban setting in southern India

Introduction

Haemophilus influenzae type b was the leading cause of bacterial meningitis in infants and children below the age of two years prior to the introduction of H. influenzae type b conjugate vaccines. In December 2011, the Indian government introduced H. influenzae b vaccine in the state of Tamilnadu. A prospective surveillance for bacterial meningitis was established at the Institute of Child Health in Chennai to evaluate the etiology of meningitis and impact of the vaccine.

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.     

Epidemiology of Haemophilus influenzae type b meningitis in Israel, 1981-90

BACKGROUND AND METHODS. In the Western world, Haemophilus influenzae type b is an important cause of morbidity and long-term disability in children. The availability of vaccines capable of preventing H. influenzae type b disease in very young infants stimulated this longitudinal observational review of the epidemiology of H. influenzae type b meningitis in Israel, based on cases reported to the Ministry of Health in the decade 1981-90. RESULTS. In the last decade, H. influenzae type b accounted for 884 cases of meningitis, making it the main cause of bacterial meningitis in children. Almost all cases were in children under the age of 5 years, the great majority under 18 months. Age-standardized incidence rates were the same in Jews and in non-Jews, and in both sectors incidence was slightly higher in males than in females. The case fatality rate was 3.3%. CONCLUSIONS. The new Haemophilus b conjugate vaccines are reported to be safe, effective at an early age, and compatible with current vaccination schedules. Their availability means that control of invasive disease caused by this organism is within reach. Use of the vaccines in infants should be encouraged and their effect on morbidity patterns should be closely monitored.     

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.     

2015-2017年湖北省含B型流感嗜血杆菌成分疫苗安全性分析

目的 分析2015-2017年湖北省3种含B型流感嗜血杆菌成分疫苗的疑似预防接种异常反应(adverse events following immunization,AEFI)发生特征,评价预防接种安全性。方法 收集2015-2017年湖北省在中国AEFI信息管理系统接种报告的B型流感嗜血杆菌结合疫苗(Hib)、DTaP-b型流感嗜血杆菌联合疫苗(DTaP-Hib)与DTaP-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗(DTaP-IPV/Hib)个案数据,采用描述性流行病学方法分析。结果 2015-2017年湖北省共报告含B型流感嗜血杆菌成分疫苗的AEFI 1391例(50.80/10万剂),其中一般反应1276例(46.60/10万剂),异常反应100例(3.65/10万剂);Hib、DTaP-Hib、DTaP-IPV/Hib 3种疫苗的AEFI分别为753例(37.40/10万剂)、354例(88.41/10万剂)、284例(87.56/10万剂)。DTaP-Hib和DTaP-IPV/Hib疫苗一般反应报告发生率高于Hib疫苗一般反应报告发生率;3种疫苗加强免疫报告发生率高于基础免疫报告发生率。3种疫苗一般反应均以发热(27.61/10万剂)、局部红肿(21.51/10万剂)、局部硬结(10.19/10万剂)为主;异常反应主要为过敏性皮疹(3.36/10万剂)。结论 含B型流感嗜血杆菌成分的3种疫苗AEFI报告发生率较低,均具有良好的安全性。     

Serotyping discrepancies in Haemophilus influenzae type b disease--United States, 1998-1999

Since Haemophilus influenzae type b (Hib) conjugate vaccines were introduced in the United States in 1990, the incidence of Hib invasive disease has declined markedly. The majority of cases of Haemophilus influenzae (Hi) disease are caused by organisms with capsule types other than b or by nontypeable organisms. One of the national health objectives for 2010 is to reduce to zero indigenous Hib invasive disease cases in children aged <5 years (objective 14-1c). In 2000, a total of 297 cases of invasive Hi disease were reported in children aged <5 years; serotype b represented 51 (22%) of 236 cases for which serotype information was known. This report describes inconsistencies in Hib serotyping between state health departments and CDC; these inconsistencies suggest that the burden of Hib disease might be less than estimated previously. Accurate laboratory information is essential for the accurate assessment of progress toward the elimination of Hib in the United States.     

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.