Acute bacterial meningitis in infants and children: epidemiology and management

Acute bacterial meningitis (ABM) continues to be associated with high mortality and morbidity, despite advances in antimicrobial therapy. The causative organism varies with age, immune function, immunization status, and geographic region, and empiric therapy for meningitis is based on these factors. Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis cause the majority of cases of ABM. Disease epidemiology is changing rapidly due to immunization practices and changing bacterial resistance patterns. Hib was the leading cause of meningitis in children prior to the introduction of an effective vaccination. In those countries where Hib vaccine is a part of the routine infant immunization schedule, Hib has now been virtually eradicated as a cause of childhood meningitis. Vaccines have also been introduced for pneumococcal and meningococcal diseases, which have significantly changed the disease profile. Where routine pneumococcal immunization has been introduced there has been a reported increase in invasive pneumococcal disease due to non-vaccine serotypes. In those parts of the world that have introduced conjugate meningococcal vaccines, there has been a significant change in the epidemiology of meningococcal meningitis. As a part of the United Nations Millennium Development Goal 4, the WHO has introduced a new vaccine policy to improve vaccine availability in resource poor countries. In addition, antibiotic resistance is an increasing problem, especially with pneumococcal infection. Effective treatment focuses on early recognition and use of effective antibiotics. This review will attempt to focus on the changing epidemiology of ABM in pediatric patients due to vaccination, the changing patterns of infecting bacterial serotypes due to vaccination, and on antibiotic resistance and its impact on current management strategies.     

New generation typhoid vaccines: an effective preventive strategy to control typhoid fever in developing countries

Typhoid fever is a serious systemic infection, caused by the enteric pathogen Salmonella enterica serovar Typhi, a highly virulent and invasive enteric bacterium. This disease occurs in all parts of world where water supplies and sanitation are substandard. These pathogens then travel to food, drinks and water through house-flies and other vectors. Globally, an estimated 12-33 million cases of enteric fever occur with 216,00-600,000 deaths per year, almost exclusively in the developing countries. Health surveys conducted by the Health Ministry of India in the community development areas indicated a morbidity rate varying from 102-2219/100,000 population in different parts of the country. A limited study in an urban slum showed 1% of children up to 17 years of age suffer from typhoid fever annually. The continued high burden of typhoid fever and the alarming spread of antibiotic resistant strains led the World Health Organization (WHO), almost ten years ago, to recommend immunization using the two new-generation vaccines in school- aged children in areas where typhoid fever posed a significant problem and where antibiotic resistant strains were prevalent. Morbidity and mortality due to high incidence of typhoid fever favors the introduction of typhoid vaccine in routine immunization in India. This vaccine should be given at the age of 2 years with Vi antigen vaccine and at least one more dose be given at 5 years of age.     

Bacterial meningitis: the impact of vaccination

Acute bacterial meningitis remains an important cause of morbidity and mortality in children. Children <2 years of age are particularly susceptible to infection with encapsulated bacteria due to their immature response to polysaccharide antigens. Conjugate vaccines, which induce T cell memory, can provide immunological protection for these children. The Haemophilus influenzae type b (Hib) conjugate vaccine was the first such vaccine to become available. The efficacy of the vaccine has been quoted as being 98%. Its introduction was followed by a dramatic decrease in the incidence of all invasive Hib disease, including meningitis. This reduction was in part due to the ability of these vaccines to reduce nasopharyngeal carriage of the organism and thereby induce herd immunity. Different Hib vaccines use a variety of protein carriers and differ in their immunogenicity and efficacy. The most suitable vaccine needs to be determined according to the local epidemiology of Hib disease. Commercial combination vaccines may lead to lower antibody levels. A recent increase in the incidence of Hib disease in the UK highlights the importance of continued surveillance and the need for booster vaccinations to ensure continued protection. Conjugate vaccines to Streptococcus pneumoniae and Neisseria meningitidis have been developed. The introduction of a pneumococcal conjugate vaccine in the US has led to a decrease in the rate of infection by nearly 60% in children <5 years of age. A reduction in pneumococcal carriage may also modify disease epidemiology. The UK introduced the conjugate meningococcal C vaccine into its infant schedule with a corresponding reduction in N. meningitidis group C disease. A recent decrease in the effectiveness of the vaccine, however, suggests a booster may be necessary in the future. Our present understanding of the immunology of conjugate vaccines is far from complete. Developed countries have introduced conjugate vaccines into their immunisation schedules to prevent bacterial meningitis; however, their high cost precludes their use in many developing countries. Progress needs to be made in order to get these highly effective vaccines to those areas that need them.     

Immunologic response to Hib tetanus toxoid conjugated vaccine coadministered with DTPa either mixed or in two separate injections in toddlers not primed with Hib vaccine

This open randomized study compared the immunogenicity and safety of a diphtheria-tetanus-acellular pertussis (DTPa) and H. influenzae polyribosylribitol phosphate conjugated to the tetanus toxoid (Hib-PRP-T) vaccine (mixed prior to administration) with separate injections of DTPa and Hib vaccines in toddlers aged two years. A total of 119 children (60 mixed; 59 separate administration), primed with DTPw, but not with Hib vaccine were enrolled. Prior to immunization only 10.3% of toddlers had anti-PRP antibody titres > or =1.0 microg/ml, compared with all children on Days 7 and 30. The anti-PRP and anti-tetanus antibody geometric mean concentrations were lower after the combined DTPa/Hib vaccine compared to separately administered vaccines (47.16 microg/ml vs 78.36 microg/ml and 24.95 IU/ml vs 40.63 IU/ml, respectively). One month after vaccination all children had anti-tetanus and anti-diphtheria antibody titres above the protective level of > or =0.1 IU/ml. The rates of recorded adverse events were similar and mostly mild or moderate in intensity whether the vaccines were combined as a single injection or given separately. We conclude that in 2-year old children, previously not immunized against Hib, a single dose of DTPa and Hib was safe and highly immunogenic irrespective of whether it was given as a combined vaccine or separate injections. Although the increase in anti-T and early (7-10 days after) anti-PRP concentrations was greater when the vaccine components were given separately than after combined administration, the DTPa/Hib combined vaccine would provide an effective method of delivering primary Hib vaccination in unprimed toddlers.     

Cost-benefit analysis of a Haemophilus influenzae type b meningitis prevention programme in The Philippines

BACKGROUND: Haemophilus influenzae type b (Hib) meningitis is associated with high mortality and serious sequelae in children under 5 years of age. Vaccines which can prevent this infection are available. OBJECTIVE: To evaluate the costs and benefits of a 3-dose immunisation schedule in Manila, Philippines. PERSPECTIVE: Government and societal perspectives. DESIGN AND PARTICIPANTS: A cost-benefit analysis based on a birth cohort of 100,000 children. The state of health of the cohort with and without a Hib immunisation programme was modelled over a 5-year period. A survey of medical records of patients with Hib in Manila provided data on the extent and cost of sequelae following infection. INTERVENTION: A 3-dose Hib vaccination programme given at ages 2, 3 and 4 months. RESULTS: The model predicted that vaccinating children against Hib meningitis would prevent 553 cases per year in a birth cohort of 100,000, at a cost of 56,200 Philippine pesos (PHP) [$US1,605; 1998 exchange rate] per case (base case assumptions of 90% vaccine efficacy rate, 95 per 100,000 Hib incidence rate, 85% vaccination coverage). Results from the cost-benefit analyses indicated that the saving to the government would be around PHP39 million ($US1.11 million), and the saving to society would be PHP255 million ($US7.28 million). CONCLUSION: There would be a positive economic benefit for the Philippine government and for the Filipino society if a Hib vaccination programme was introduced in Manila.     

Introduction of a second dose of measles in national immunization program in India: a major step towards eradication

Measles is a highly infectious, acute respiratory illness that is caused by a virus of the genus Morbillivirus. The disease infects nearly 30 million children each year, and deaths usually occur from complications related to pneumonia, diarrhea and malnutrition. A systematic review of published Indian literature depicts the median case fatality ratio (CFR) of measles to be 1.6%. Through immunization, measles deaths dropped a remarkable 78% from 733,000 in 2000 to 164,000 in 2008. As of 2008, 192 of 193 Member States of WHO use 2 doses of measles vaccine in their national immunization programs, India being the only exception. The Millennium Development Goal (MDG) 4 aims to reduce by two-thirds between 1990 and 2015 the under-five mortality rate (U5MR) in the world. Per the draft comprehensive Multi Year Strategic Plan (cMYP, 2010–17) for immunization of India, the country aims to reduce measles-related mortality by 90% by 2013 when compared to 2000. As recommended by the National Technical Advisory Group on Immunization (NTAGI), the implementation strategy of the second dose of measles vaccine at the state level is determined by the underlying performance of the routine immunization program. The second dose in the national immunization schedule gives extra immunity against measles infection that renders children more susceptible to secondary pneumonia and diarrheal diseases, which are the primary causes of under-5 child mortality in India.     

Live attenuated influenza vaccine (FluMist®; Fluenz™): a review of its use in the prevention of seasonal influenza in children and adults

Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B). LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged ≤71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenza caused by antigenically-matching viral strains in a multinational phase III trial in children aged 6-59 months. LAIV was also significantly more effective than TIV in decreasing the incidence of culture-confirmed influenza illness in two open-label studies (in children with recurrent respiratory tract illnesses aged 6-71 months and in children and adolescents with asthma aged 6-17 years). LAIV did not differ significantly from placebo in preventing febrile illnesses in adults (primary endpoint) enrolled in a phase III trial. However, LAIV significantly reduced the incidence of febrile upper respiratory tract illnesses (URTI), severe febrile illnesses, febrile URTI-related work absenteeism and healthcare provider use. In another well designed trial in adults, LAIV significantly reduced the incidence of symptomatic, laboratory-confirmed influenza compared with placebo (but not intramuscular TIV). LAIV was generally well tolerated in most age groups, with the majority of adverse events being mild to moderate in severity, and runny nose/nasal congestion being the most common. In a large phase III trial, LAIV, compared with TIV, was associated with an increased incidence of medically significant wheezing in vaccine-naive children aged <24 months and an increased incidence of hospitalization in children aged 6-11 months; LAIV is not approved for use in children <24 months. LAIV was not always associated with high rates of seroconversion/seroresponse, particularly in older children and adults, or in subjects with detectable levels of haemagglutination-inhibiting antibodies at baseline. However, LAIV did elicit mucosal (nasal) IgA antibody responses and strong cell-mediated immunity responses. Only one confirmed case of LAIV virus transmission to a placebo recipient (who did not become ill) occurred in a transmission study conducted in young children. The immunogenic response to LAIV in young healthy children was not affected by concomitant administration with other commonly administered childhood vaccines. In conclusion, intranasal LAIV seasonal influenza vaccine is effective and well tolerated in children, adolescents and adults. LAIV was more effective than TIV in children, although this advantage was not seen in adults. In the US, LAIV is indicated for the active immunization of healthy subjects aged 2-49 years against influenza disease caused by virus subtypes A and type B contained in the vaccine.     

Preventing Haemophilus influenzae type b disease

The pathogenesis of Haemophilus influenzae type b (Hib) disease and methods for limiting spread of outbreaks of Hib disease are reviewed. Many strains of H. influenzae are surrounded by an outer polysaccharide capsule; of the six antigenically distinct capsular types, Hib is the predominant cause of such serious infections as meningitis, especially among children younger than five years of age. The age-specific incidence of Hib disease appears to be related to the relatively small concentrations of anti-Hib antibody present in young children. Children younger than 48 months of age who reside in the same house or attend the same day-care center as a child who develops Hib disease appear to be at increased risk for contracting systemic Hib infections. Prophylactic administration of rifampin 20 mg/kg once daily for four days can substantially decrease asymptomatic carriage of Hib in household contacts of the index patient and reduce the incidence of secondary Hib disease. The index patient should also receive prophylactic rifampin therapy before discharge from the hospital; i.v. antibiotics may cure the systemic infection but allow nasopharyngeal colonization to persist. A vaccine formulated from purified Hib capsular polysaccharide confers protection to more than 90% of children vaccinated at a minimum age of 24 months. Other candidates for vaccination include children between the ages of two and five years who attend day-care centers and children with anatomic or functional asplenia or malignancies. The vaccine is not effective in children younger than 18 months of age (who account for 60% of Hib disease in the U.S.); methods to increase vaccine immunogenicity in young infants are being evaluated. Reduction of Hib disease in the U.S. may be possible through widespread use of the new vaccine.     

Haemophilus influenzae type b conjugate vaccines: considerations for vaccination schedules and implications for developing countries

Prior to widespread vaccination, Haemophilus influenzae type b was a leading cause of severe childhood bacterial infection, including meningitis, worldwide. Over the last decade the world has taken great strides towards controlling Hib disease through routine use of conjugate vaccines in developed and developing countries. Currently there is no consensus on the appropriate schedule by which to use Hib vaccine. Vaccination schedules around the world vary greatly, particularly between high and low income countries. Questions remain as to the most effective and efficient schedule of primary doses, the need for a booster dose, and the implications of using combination vaccines. Here, we present a synthesis of data supporting various Hib vaccine schedules, with a focus on the implications for developing countries.     

23价肺炎球菌多糖疫苗研究进展

肺炎球菌是导致成人和儿童罹患肺炎疾病住院甚至死亡的重要原因。肺炎球菌的91个血清型中有20种血清型与各年龄组超过85%的侵袭性肺炎球菌感染有关。根据23种引起85%～90%的引起肺炎球菌感染疾病的血清型研制而成的23价肺炎球菌多糖疫苗,具有很好的安全性,成人和>2岁儿童接种后会产生可靠的免疫力,在人群中保护率达50%～80%,具有较好的成本效益比,是儿童和成人预防肺炎球菌感染的有效措施,推荐用于60岁以上老年人和2岁以上体弱儿童和慢性疾病患者。本文主要对23价肺炎球菌多糖疫苗的安全性、免疫反应、保护率及成本效益、对特殊健康状况人群的保护效果和免疫策略作一综述。     

Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developing countries

This article provides an overview of the clinical profile of rotavirus vaccine RIX4414 (Rotarix?) in the prevention of rotavirus gastroenteritis (RVGE) in developing countries, followed by a comprehensive review of pharmacoeconomic analyses with the vaccine in low- and middle-income countries. RVGE is associated with significant morbidity and mortality among children <5 years of age in developing countries. The protective efficacy of a two-dose oral series of rotavirus vaccine RIX4414 has been demonstrated in several well designed clinical trials conducted in developing countries, and the 'real-world' effectiveness of the vaccine has also been shown in naturalistic and case-control trials after the introduction of universal vaccination programmes with RIX4414 in Latin American countries. The WHO recommends universal rotavirus vaccination programmes for all countries. Numerous modelled cost-effectiveness analyses have been conducted with rotavirus vaccine RIX4414 across a wide range of low- and middle-income countries. Although data sources and assumptions varied across studies, results of the analyses consistently showed that the introduction of the vaccine as part of a national vaccination programme would be very (or highly) cost effective compared with no rotavirus vaccination programme, according to widely used cost-effectiveness thresholds for developing countries. Vaccine price was not known at the time the analyses were conducted and had to be estimated. In sensitivity analyses, rotavirus vaccine RIX4414 generally remained cost effective at the highest of a range of possible vaccine prices considered. Despite these favourable results, decisions regarding the implementation of universal vaccination programmes with RIX4414 may also be contingent on budgetary and other factors, underscoring the importance of subsidized vaccination programmes for poor countries through the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization).     

A live attenuated human rotavirus vaccine

Rotavirus infections are the leading cause of severe gastroenteritis in young children worldwide. This review provides a summary of the development of a live oral rotavirus vaccine, Rotarix (GlaxoSmithKline, Rixensart, Belgium) developed from a single protective G1P[8] human strain. To attenuate the wild-type virus, the original isolate, 89-12, was passaged multiple times in tissue culture. Large safety and efficacy trials that have included more than 100,000 children around the world have shown the vaccine is safe and not associated with intussusception. The vaccine is highly immunogenic and protective against disease caused by all the most common circulating human serotypes. Efficacy against severe rotavirus gastroenteritis and hospitalization has ranged from 85-100%. Rotarix is available in the European Union, most countries in Latin America, Australia, and numerous other countries around the world. The vaccine is administered as two oral doses with at least four weeks between doses. The first dose may be administered from the age of 6 weeks, and both doses should be completed by 24 weeks of age.     

Sudden unexpected death in infants under 3 months of age and vaccination status- -a case-control study

AIMS: To determine whether DTPP+Hib vaccination (diphtheria, tetanus, pertussis, poliomyelitis +/- haemophilus) increased the risk of sudden unexpected death (SUD) in children under 3 months of age. METHODS: We conducted a multicentre case-control study in the 28 French 'SIDS Centers'. Case selection was based on death labelled sudden infant death syndrome (SIDS) of an infant aged between 30 and 90 days. Three living controls were selected, matched for sex, gestational age and born immediately after the victim in the same maternity unit. RESULTS: We identified 114 cases of SUD aged between 30 and 90 days and 341 live controls matched for age and sex and born in the same maternity unit as the case. DTPP+/-Hib immunization did not increase the risk of SUD (OR 1.08) (95% CI 0.49, 2.36) in children under 3 months of age when adjusted for sleeping position, illness in the week before death, maternal tobacco consumption, birth weight, type of mattress, breastfeeding and sex. However, low birth-weight (6.53 [2.29, 18.9]), multiple birth (5.1 [1.76, 15.13]), no breastfeeding (1.77 [1.1, 2.85]), prone sleeping position (9.8 [5, 8, 18, 9]), soft mattress (3.26 [1.69, 6.29]), recent illness (3.44 [1.84, 6.41]) and parental smoking (1.74 [1.2, 2.96]) were confirmed as risk factors in early SIDS. CONCLUSIONS: DTPP+/-Hib immunization is not a risk factor for early SUD. In this population, we found the same risk factors as described for SIDS.     

Streptococcus pneumoniae bacteraemia in children

Occult bacteraemia is the most frequent invasive disease caused by Streptococcus pneumoniae in children less than 3 years of age. Despite the relative frequency of this infection, its management is still a challenging task for paediatricians because fever is often the only symptom and a considerable overlap exists in the clinical presentation of children with fever without a focus due to viral illness and children with occult bacteraemia. Management protocols take into account the age of the patient, the clinical score for severity and the results of laboratory tests such as the white blood cell count, the C-reactive protein and the blood procalcitonin level in order to define accurately who will benefit from an antibiotic treatment. Despite appropriate healthcare facilities and access to care the case fatality rate in developed countries is around 9% in children aged less than 1 year. Prevention with the 7-valent conjugate vaccine against S. pneumoniae will decrease morbidity and mortality associated with invasive disease due to these bacteria. However, replacement by non-vaccine serotypes has been noted in countries where the vaccine is widely used and this concern needs to be monitored carefully over the next few years.     

吉水县2010年麻疹疫苗强化免疫的效果分析

目的 总结评价吉水县2010年麻疹疫苗强化免疫的效果,探讨控制麻疹的策略.方法 按照《2010年江西省麻疹疫苗强化免疫活动实施方案》的要求实施,采用描述性方法对相关数据进行流行病学分析.结果 本次强化免疫8个月～4岁应种儿童23 256名,实种儿童22 896名,实际接种率达98.45％,快速评估接种率97.75％.强化免疫期间,全县共报告麻疹相关疑似预防接种异常反应1例,发生率4.37/10万.没有发生因麻疹疫苗强化免疫引起的群体事件,无疫苗质量事故和实施差错事故报告,无死亡病例发生.实施麻疹疫苗强化免疫后麻疹发病率大幅下降.结论 吉水县2010年麻疹疫苗强化免疫活动目标儿童麻疹疫苗接种率＞95％,达到预期目的.     

Pneumococcal conjugate vaccine (Prevnar; PNCRM7): a review of its use in the prevention of Streptococcus pneumoniae infection

PNCRM7 (Prevnar) is a pneumococcal vaccine containing seven capsular polysaccharide antigens from the bacterium Streptococcus pneumoniae, each of which is conjugated to diphtheria protein [cross-reactive material (CRM(197))]. CRM(197) is an inert but immunogenic variant of diphtheria toxoid that is also used as a carrier molecule in one Haemophilus influenzae type b conjugate vaccine. Unlike the 23-valent unconjugated pneumococcal vaccines, PNCRM7 elicits a T cell-dependent response and thus protects young children against pneumococcal disease. The immunogenicity of PNCRM7 has been demonstrated in both healthy children aged <2 years and older children in high-risk groups. Two randomized, double-blind trials conducted in the US demonstrated that all PNCRM7 serotypes were immunogenic in healthy infants and young children when compared with a control vaccine. A booster dose of PNCRM7 elicited an anamnestic response to all seven serotypes. Data from a large, randomized, double-blind study conducted in California (US) have confirmed the protective efficacy of PNCRM7 against invasive pneumococcal disease (e.g. bacteremia, meningitis) caused by serotypes included in the vaccine. The vaccine efficacy in the per-protocol analysis was 97.4% and its efficacy against invasive disease caused by any pneumococcal serotype in the intent-to-treat (ITT) analysis was 89.1%. Indeed, a postlicense surveillance study (n = 211,565) showed that the introduction and routine use of PNCRM7 was associated with a marked reduction in invasive pneumococcal disease in children <5 years of age. In addition, the US trial and another randomized, double-blind trial conducted in Finland, showed that PNCRM7 vaccine efficacy against all otitis media episodes was between 6 and 7%. PNCRM7 vaccine was generally well tolerated and had a similar local and systemic adverse events profile to other pediatric vaccines. The most common local adverse event associated with PNCRM7 administration was inflammation at the injection site, and the most common systemic adverse effect was febrile illness (> or =38 degrees C) that usually resolved without treatment. The limited available pharmacoeconomic data suggest that PNCRM7 could be cost effective depending, in part, on the manufacturer's list price of the vaccine. Results of the base case analysis in a US study showed a cost-effectiveness ratio for PNCRM7 of US dollars 80,000 per life-year saved from a societal perspective compared with US dollars 176,000 from a healthcare payer perspective, assuming a nondiscounted list price of US dollars 58 per dose (1997 costs). Concomitant administration of PNCRM7 vaccine with hepatitis B, oral polio, meningococcal oligosaccharide protein conjugate or H. influenzae type b vaccines did not affect the immunogenicity of these pediatric vaccines to a clinically relevant extent. CONCLUSION: PNCRM7 vaccine will be of great benefit to those societies that have active immunization programs implemented. In infants and vulnerable children throughout the world, PNCRM7 vaccine has the potential to reduce the mortality and morbidity rates associated with S. pneumoniae infections. In developed countries, the vaccine will be of particular benefit in preventing disabling infections but its impact in developing countries will be more pronounced with the potential to greatly reduce mortality.     

23价肺炎链球菌多糖疫苗和13价肺炎链球菌结合疫苗在成年人中的应用

 肺炎链球菌是引起全球不同年龄人群,尤其是幼儿和老年人肺炎、败血症和脑膜炎等严重疾病的重要病原菌,由肺炎链球菌导致的这些疾病可以通过疫苗进行预防。在将肺炎链球菌疫苗纳入国家免疫计划的国家,儿童肺炎链球菌病的发病率以及疫苗型肺炎链球菌的携带率大大降低,且可在未免疫人群中产生间接保护作用。此文对23价肺炎链球菌多糖疫苗和13价肺炎链球菌结合疫苗在成年人中的应用进行探讨。     

The continuing role of Haemophilus influenzae type b carriage surveillance as a mechanism for early detection of invasive disease activity

Prior to the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, Hib was the leading cause of bacterial meningitis in children under five years of age worldwide. In countries that have adopted Hib vaccination schedules, invasive disease has reduced markedly. Oro-naso pharyngeal carriage is recognized as the most significant source of infection. Hib carriage is significantly associated with poverty, such as overcrowding, poor ventilation in houses, lack of running water, and high smoking rates. Additionally, many Indigenous minority groups report high rates of Hib carriage. A resurgence of Hib disease among Alaskan children in the 1990s, lead to a change in approach to eliminate Hib disease and carriage in high-risk populations. This new approach identifies strategies for eliminating Hib disease focusing on the reservoirs of colonization within families and communities. Monitoring Hib carriage continues to offer an early warning system, whereby intervention could prevent invasive disease resurgence.     

宝安区6~15岁在校儿童高浓度麻疹IgG抗体影响因素研究

目的研究分析宝安区6~15岁在校儿童高浓度麻疹免疫球蛋白G(IgG)抗体影响因素。方法研究共调查宝安区6~15岁在校儿童444例,均采集静脉血1 ml,分离血清并进行麻疹IgG抗体的定量酶联免疫吸附试验(ELISA)检测,并对高浓度麻疹IgG抗体影响因素进行单因素及多因素分析。结果单因素分析结果显示:年龄、父亲文化程度、母亲文化程度、麻疹疫苗接种剂次、首针接种月龄是6~15岁在校儿童高浓度麻疹IgG抗体的影响因素,差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,年龄、首针接种月龄为6~15岁在校儿童高浓度麻疹IgG抗体的主要危险因素,差异具有统计学意义(P<0.05)。结论儿童麻疹发病的预防控制,对于麻疹疫苗首剂的接种,可以考虑将首剂接种月龄延后,以提高疫苗的效力。对于该年龄段的儿童可以考虑结合实际情况,适时进行加强免疫。     

Spotlight on Tdap₅ vaccine (Covaxis®) as a single-booster immunization for the prevention of tetanus, diphtheria, and pertussis: in children (aged ≥4 years), adolescents, and adults

Covaxis? (also licensed as Triaxis? or Adacel? in individual countries) is a Tdap? (i.e. combined tetanus toxoid, reduced diphtheria toxoid, five component acellular pertussis [namely detoxified pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3]) vaccine for the prevention of diphtheria, tetanus, and pertussis. It is approved for use in Europe as a single intramuscular booster dose in children (aged ≥4 years), adolescents, and adults, and in the US it is approved for use in individuals aged 11-64 years. In large, randomized, controlled clinical trials conducted in the UK and North America, a single intramuscular booster dose of Covaxis? induced robust immune responses for all of its component antigens when given to children (aged ≥4 years), adolescents, and adults. In addition, Covaxis? vaccine was safe and generally well tolerated in terms of solicited and unsolicited local injection-site and systemic adverse events, most of which were of mild intensity and resolved without sequelae. Furthermore, the immunogenicity of each individual component and the reactogenicity of Covaxis? vaccine in children, adolescents, and adults was generally similar to that of comparator vaccines. Despite being a vaccine-preventable disease and having >90% primary vaccination coverage worldwide, pertussis remains uncontrolled, particularly amongst adolescents and adults. Given the changing epidemiology of pertussis and the requirement to reduce infection in adolescents and adults (including healthcare workers) and thereby prevent transmission of the disease from these individuals to very young infants, the new 'cocoon strategy' recommended in current vaccination guidelines has become a key strategy in the management of morbidity and mortality associated with pertussis. This strategy focuses on the immunization of healthcare workers, and the parents and family members of infants who are too young to have undergone primary immunization, so as to prevent the transmission of pertussis to these young at-risk infants. The implementation of the 'cocoon strategy' may finally give countries the ability to control pertussis infections in these at-risk infants and ultimately provide the desired herd immunity against pertussis. In line with this strategy, a booster dose of Covaxis? vaccine provides a valuable option to reduce pertussis morbidity and mortality, and to maintain seroprotection against diphtheria and tetanus in children (aged ≥4 years), adolescents, and adults.