A prospective study of etiology of childhood acute bacterial meningitis, Turkey

Determination of the etiology of bacterial meningitis and estimating cost of disease are important in guiding vaccination policies. To determine the incidence and etiology of meningitis in Turkey, cerebrospinal fluid (CSF) samples were obtained prospectively from children (1 month-17 years of age) with a clinical diagnosis of acute bacterial meningitis. Multiplex PCR was used to detect DNA evidence of Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis. In total, 408 CSF samples were collected, and bacterial etiology was determined in 243 cases; N. meningitidis was detected in 56.5%, S. pneumoniae in 22.5%, and Hib in 20.5% of the PCR-positive samples. Among N. meningitidis-positive CSF samples, 42.7%, 31.1%, 2.2%, and 0.7% belonged to serogroups W-135, B, Y, and A, respectively. This study highlights the emergence of serogroup W-135 disease in Turkey and concludes that vaccines to prevent meningococcal disease in this region must provide reliable protection against this serogroup.     

Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children

To determine incidence of invasive Haemophilus influenzae type b (Hib) disease in a defined population of Jeonbuk Province, Korea, children <5 years were evaluated in prospective, population-based surveillance of invasive bacterial diseases using standardized methods for patient referral, clinical evaluation and laboratory testing (optimized culture, latex agglutination, polymerase chain reaction). Vaccine utilization was assessed with vaccination histories of patients in surveillance, monthly data on Hib vaccine distribution and a coverage survey of clinic patients in study population. From September 1999 to December 2001, 2176 children were evaluated for possible meningitis, 1541 had no cerebrospinal fluid (CSF) findings of meningitis, 605 had CSF abnormalities (suspected bacterial meningitis) but no pathogen identified; six patients had probable Hib meningitis and eight had confirmed Hib meningitis. The annual suspected bacterial meningitis incidence was 258.4/100,000 <5 years and the probable/confirmed Hib meningitis incidence was 6.0/100,000 <5 years. Pneumococcal meningitis incidence was 2.1/100,000 <5 years and Group B streptococcal meningitis incidence was 0.17/1000 live births. A total of 69,589 Hib vaccine doses were distributed during the study. Hib vaccine coverage was negligible initially but increased to 16% (complete Hib immunization) and 27% (partial immunization) in final months of study. Suspected bacterial meningitis incidence was high but proven invasive Hib meningitis incidence was low. Hib was leading cause of bacterial meningitis yet bacterial pathogens were identified in only 4% of abnormal CSF. These findings may reflect truly low incidence, presumptive antibiotic treatment, partial Hib immunization, or incomplete clinical evaluations. Given the apparent Hib meningitis burden in Jeonbuk Province, additional studies to describe other invasive Hib syndromes, Hib-associated mortality and disability, and economic impact of Hib disease will be useful to guide public health decisions regarding routine Hib vaccine introduction.     

Incidence of bacterial meningitis in Asia using enhanced CSF testing: polymerase chain reaction, latex agglutination and culture

To enhance the detection of bacterial meningitis in an East Asian surveillance study, we employed cerebrospinal fluid (CSF) bacterial culture, latex agglutination (LA) and polymerase chain reaction-enzyme immunoassay (PCR-EIA) testing for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). The sensitivity and specificity of CSF PCR-EIA testing was compared to LA and culture. A meningitis case was defined by one positive result for any of the three tests. The sensitivity of H. influenzae CSF PCR-EIA, LA, and culture was 100%, 40% and 57.5% respectively; and for Sp CSF PCR-EIA, LA and culture, the sensitivity was 100%, 58.3% and 66.7%, respectively. Hib and Sp specificity was 100% by each method. CSF PCR-EIA was more sensitive than culture or LA for the detection of Hib and Sp meningitis cases increasing their incidence by 74% and 50% compared to culture respectively. CSF PCR-EIA should be included for the detection of bacterial meningitis in surveillance studies.     

Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective,population-based surveillance study

OBJECTIVE: To assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria. METHODS: From 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions. For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity. FINDINGS: During the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group. Overall, 285 children with suspected meningitis were identified. In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained. Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination. An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis. There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10%. Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins. CONCLUSION: On the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health. The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins.     

Epidemiology of bacterial meningitis in Niamey, Niger, 1981-96.

In the African meningitis belt the importance of endemic meningitis is not as well recognized as that of epidemics of meningococcal meningitis that occur from time to time. Using retrospective surveillance, we identified a total of 7078 cases of laboratory-diagnosed bacterial meningitis in Niamey, Niger, from 1981 to 1996. The majority (57.7%) were caused by Neisseria meningitidis, followed by Streptococcus pneumoniae (13.2%) and Haemophilus influenzae b (Hib) (9.5%). The mean annual incidence of bacterial meningitis was 101 per 100,000 population (70 per 100,000 during 11 non-epidemic years) and the average annual mortality rate was 17 deaths per 100,000. Over a 7-year period (including one major epidemic year) for which data were available, S. pneumoniae and Hib together caused more meningitis deaths than N. meningitidis. Meningitis cases were more common among males and occurred mostly during the dry season. Serogroup A caused 85.6% of meningococcal meningitis cases during the period investigated; three-quarters of these occurred among children aged < 15 years, and over 40% among under-5-year-olds. Both incidence and mortality rates were highest among infants aged < 1 year. In this age group, Hib was the leading cause of bacterial meningitis, followed by S. pneumoniae. The predominant cause of meningitis in persons aged 1-40 years was N. meningitidis. Use of the available vaccines against meningitis due to N. meningitidis, S. pneumoniae, and Hib could prevent substantial endemic illness and deaths in sub-Saharan Africa, and potentially prevent recurrent meningococcal epidemics.     

Impact of Haemophilus influenzae b (Hib) vaccination on meningitis in Central Brazil

OBJECTIVE: To assess the impact of the Haemophilus influenzae b (Hib) conjugate vaccine in reducing the incidence of meningitis among children under five years old. METHODS: A 'before-after' design was used to compare Hib meningitis incidence rates in the pre-vaccine (July 1995 - June 1999) and post-vaccine (July 1999 - June 2001) periods in the state of Goias, central Brazil. Bacterial meningitis case definition was based on World Health Organization criteria. Incidence rates of S. pneumoniae and N. meningitidis were used for comparison purposes. Chi-squared and Student's t tests were used for statistical analysis. P-values below 0.05 were considered as statistically significant. RESULTS: 979 children with acute bacterial meningitis were detected throughout the entire period. The incidence rate of Hib meningitis decreased from 10.8 (x10(5)) in the pre-vaccine period to 2.3 (x10(5)) in the 2nd year post vaccination, leading to a risk reduction of 78%, targeted to the 7-23 months age group (p<0.05). A total of 65 cases of Hib meningitis were prevented. An increase in S. pneumoniae meningitis was observed. Vaccine failure was detected in one child. CONCLUSIONS: This study showed that mass immunization with Hib conjugate vaccine brought about an expressive decline in childhood Hib meningitis in Goias soon after the first year. Notwithstanding, an enhancement of surveillance using high-accuracy tools is essential to: (i) detect a possible reemergence of Hib; (ii) identify vaccine failure, and (iii) monitor changes in the H. influenzae serotype profile over time.     

Detection of acute childhood meningitis by PCR, culture and agglutination tests in Tabriz, Iran

Meningitis is one of the hazardous and life threatening infections and is associated with mortality and morbidity. The aim of this study was to determine etiological agents of childhood bacterial meningitis. The culture, Gram staining, agglutination and PCR assays were used to examine CSF specimens from 277 patients with presumed bacterial meningitis for the occurrence of 4 most common infectious agents consist of N. meningitis, H. influnsae, S. pneumoniae and S. agalactiae between 2008 and 2009 at different wards of the Children Hospital of Tabriz. The mean age of patients was 35 ± 2 (Mean ± SEM) month, (minimum 11 days maximum 14 years), of all cases 59.6% male and 40.4% female. Overall the diagnosis was confirmed with a CSF culture in 11/277 (3.97%), by agglutination test in 14/277 (5.05%). The isolated bacteria included S. pneumoniae 5 cases, H. influnsae 2 cases, N. meningitis 3 cases and P. aeroginusae 1 case. A positive PCR assay allowed us to diagnose bacterial meningitis in 19 patients (6.8%). In the present study, we found PCR to be a useful and sensitive method for the detection of bacterial DNA in the CSF samples from suspected meningitis patients. Furthermore, to maximize management of meningitis cases, a combination of culture and PCR is necessary.     

Rapid detection of Haemophilus influenzae type b in Bangladeshi children with pneumonia and meningitis by PCR and analysis of antimicrobial resistance

A polymerase chain reaction (PCR) assay with primers from 'bexA' gene was compared with culture for the detection of Haemophilus influenzae type b (Hib) in clinical samples from children with pneumonia and meningitis. Of 200 sera (180 from pneumonia, 20 from non-pneumonia patients) tested by PCR (serum-PCR), Hib was detected in 15 of 16 blood culture-positive and in 6 blood culture-negative pneumonia cases. When compared with the results of blood culture, serum-PCR had sensitivity, specificity, and accuracy index of 93.7%, 96.7%, and 96.5% respectively. Of 120 cerebrospinal fluid (CSF) samples from meningitis patients tested by culture and PCR (CSF-PCR), the latter method could detect Hib in all 15 culture-positive and in 8 of 105 culture-negative cases, showing sensitivity, specificity, and accuracy index of 100%, 92.4%, and 94.4% respectively. The PCR result was available within a day. Antimicrobial susceptibility of Hib was determined by the disc-diffusion method. High rate of resistance to ampicillin (54.8%), chloramphenicol (48.4%), and co-trimoxazole (80.6%) was observed among 31 invasive Hib isolates with resistance to all 3 drugs (multiresistance) in 48.4% of the isolates. All the Hib isolates were susceptible to ceftriaxone. The study has shown that PCR is a rapid, sensitive and specific diagnostic test for Hib from clinical samples, and a combination of culture and PCR is necessary for the detection of Hib infections to the maximum extent for case management to reduce morbidity, mortality, and complications of the invasive Hib infections. A high prevalence of multiresistant Hib strains is a matter of concern.     

Clear and present danger: in childhood meningitis. The importance of Hib immunisation in infancy and high-risk groups

The incidence of Haemophilus influenzae type b (Hib) invasive disease has declined significantly in the United Kingdom since the introduction of routine Hib immunisation. However life-threatening Hib infections such as meningitis and epiglottitis may still occur, especially in the unimmunised and immigrant children. A case of Hib meningitis is a reminder that the threat of invasive Hib disease has not been totally eliminated. Early diagnosis and treatment of bacterial meningitis (including Hib meningitis) is essential to prevent death and serious neurological sequelae. Health visitors play a vital role in encouraging parents to have their children immunised without any avoidable delays and in providing reliable information as necessary to back up this advice. Enquiring about immunisation status of all children new to a practice and addressing any omissions, should be routine; immigrant children (and their parents) may be particularly vulnerable and more likely to be inadequately immunised.     

贵港市急性脑炎及脑膜炎症候群病原体监测

目的 了解华南地区急性脑炎及急性脑膜炎的发病强度、病原谱和流行病学特征,为急性脑炎、脑膜炎的临床诊治和预防控制提供参考依据。方法 在广西贵港市建立涵盖市辖区、桂平市和平南县的急性脑炎、脑膜炎流行病学监测网络,按照筛检标准评估疑似病例,进行流行病学调查和采样,对标本开展细菌学培养和10种常见病毒检测。结果 2007年5月—2008年10月监测期内,共评估急性脑炎及急性脑膜炎症候群病例 883例,死亡 41例,细菌学培养和PCR检测发现存在肺炎链球菌、流脑、Hib、猪链球菌等致病菌,病毒学检测发现肠道病毒、腮腺炎病毒和乙脑病毒是病毒性脑炎脑膜炎的主要病原,贵港市确诊的细菌性、病毒性脑炎脑膜炎年均发病率分别为0.92/10万和6.42/10万,细菌性、病毒性脑炎脑膜炎均以夏秋季多见,10岁以下儿童为主,职业分布细菌性脑炎脑膜炎以散居儿童和农民为主,分别占48.65%和29.73%,病毒性脑炎脑膜炎以散居儿童和学生为主,分别占59.64%和21.08%。结论 广西贵港市急性脑炎脑膜炎病例以病毒性感染占多数,病原诊断的细菌性脑炎脑膜炎发病率处于较低水平。     

Impact of anti-Hib conjugate vaccine on the incidence of Haemophilus influenzae meningitis in Brazil's Federal District: results of a three-year follow-up]

INTRODUCTION: Type b Haemophilus influenzae (Hib) continues to be an important causative agent of various infectious processes, and its encapsulated strains cause invasive disease. In some aboriginal populations, the incidence of Hib infections in children under five is greater than 400 per 100,000. In the seventies and eighties, vaccines against Hib were developed after antibodies against the capsular component were identified. The objective of this paper was to estimate the impact that the vaccine against Hib has had in Brazil's Federal District since it was introduced in March of 1998. METHODS: Using population-based data obtained from Brazil's Federal District's Ministry of Health's Surveillance System, rates of incidence of meningitis during the three years that preceded and that followed the introduction of the anti-Hib vaccine were compared. Comparisons were also drawn between changes in the trends observed. RESULTS: A comparison of the data from the two periods showed a decrease of approximately 90% in the incidence of Hib meningitis, but no concomitant decrease in other forms of bacterial meningitis was noted. There was also a proportional increase in the number of cases among infants 6 months of age and under due to a drop in the incidence of the disease in children older than 6 months. CONCLUSION: As a result of the introduction of the conjugated anti-Hib vaccine in Brazil's Federal District, the incidence of Hib meningitis among children 7 months to 35 months of age dropped from 168 per 100,000 to 15 per 100,000 (91.1%).     

细菌性脑炎/脑膜炎266例流行病学分析

目的了解急性细菌性脑炎/脑膜脑炎的流行特征与病原谱,为全国范围内开展类似研究提供科学依据。方法对监测到的细菌性脑炎/脑膜炎开展个案调查并采集血清和或脑脊液标本,开展实验室检测工作。结果 2007-05/2010-12报告的出院诊断为细菌性脑炎/脑膜脑炎患者266例,男女性别比为1.56∶1,平均年龄8.7岁,73.7%的病例集中在10岁以下儿童,各月都有病例发生,无明显发病季节高峰。19.9%病例接种过乙脑、流脑、Hib疫苗中的一种或一种以上,92.4%的病例在标本采集前使用了抗生素。实验室确诊的细菌性脑炎/脑膜脑炎病例的主要病原为肺炎链球菌、脑膜炎奈瑟菌、新型隐球菌和b型流感嗜血杆菌。结论初步了解266例细菌性脑炎/脑膜脑炎的流行特征与病原谱,为进一步研究细菌性脑炎/脑膜脑炎及其他症候群的流行病学监测提供了重要依据。     

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.     

Population-based surveillance for bacterial meningitis in the Dominican Republic: implications for control by vaccination

Quantifying the local burden of disease is an important step towards the introduction of new vaccines, such as Haemophilus influenzae type b (Hib) conjugate vaccine. We adapted a generic protocol developed by the World Health Organization for population-based surveillance of bacterial meningitis. All hospitals that admit paediatric patients with meningitis in the National District, Dominican Republic were included in the system and standard laboratory methods were used. The system identified 111 cases of confirmed bacterial meningitis. Hib was the leading cause of bacterial meningitis, followed by group B streptococcus, S. pneumoniae, and N. meningitidis. Unlike hospital-based case series, this population-based system was able to calculate incidence rates. The incidence of Hib meningitis was 13 cases per 100,000 children < 5 years old. The data from this study were used by the Ministry of Health to support the introduction of routine Hib vaccination and will be used to monitor its effectiveness.     

Rapid assessment of the impact of Haemophilus influenzae vaccine serotype b in Colombia. Public Health Laboratories]

In May 1998 the Ministry of Health of Colombia started a universal vaccination campaign against Haemophilus influenzae type b (Hib) for children under one year of age. The impact of this intervention on the incidence of acute bacterial meningitis was assessed in 1999, using data from the laboratory-based surveillance system coordinated since 1994 by the Microbiology Group of the Colombian National Institute of Health. The analysis compared the annual number of cases of Hib meningitis in children under one year of age diagnosed through the surveillance system before the vaccine was introduced with the number of cases reported during the first year after the vaccine's introduction. The expected number of cases, given the average annual number of cases diagnosed between June 1994 and June 1998, was compared with the number of cases observed after the vaccination program was introduced, from June 1998 through May 1999. To control for the quality of the surveillance system, a similar analysis was done for cases of meningitis due to Streptococcus pneumoniae. The analysis was restricted to those departments of Colombia that had consistently participated in the surveillance system. For the years 1994 through 1998 the numbers of confirmed cases of Hib meningitis were, respectively, 45, 37, 61, 64, and 31. In the period after the vaccine's introduction 31 cases were observed, as compared to the 52 expected (P < 0.001). During the same annual periods there were 32, 26, 43, 48, and 42 confirmed cases of meningitis from S. pneumoniae in children less than 5 years old, showing no significant reduction in the expected number of those cases. The 40% decrease noted in Hib meningitis cases was not attributable to changes in the surveillance system and was due mainly to the effects of the vaccination program.     

高原地区儿童脑炎脑膜炎症候群病原监测分析

目的了解高原地区脑炎脑膜炎症候群病例病原种类及其流行特征。方法收集2010年1月—2011年12月在青海省妇女儿童医院和青海红十字医院就诊的≤14岁脑炎脑膜炎症候群病例基本信息及临床信息,对所有脑脊液标本进行肺炎链球菌、脑膜炎奈瑟球菌等8种细菌的培养鉴定以及乙脑病毒等4种病毒的核酸检测。结果共有254例脑炎脑膜炎病例脑脊液标本进行了实验室检测,共检出阳性菌株21株,细菌检出率为8.27%;以金黄色葡萄球菌、结核杆菌检出率最高,各占整个阳性标本的23.81%;其次为大肠杆菌和隐球菌,各占阳性标本的19.05%;另检出肺炎链球菌和脑膜炎奈瑟球菌,分别占阳性标本的9.52%和4.76%;病毒核酸检测阳性19份,病毒检出率为7.48%,主要为肠道病毒,共15份,占整个阳性标本的78.95%,检出腮腺炎病毒和单纯疱疹病毒核酸阳性各2份,各占阳性标本的10.53%。结论高原地区脑炎脑膜炎症候群仍以细菌感染略占优势,而肠道病毒引起的脑炎也不容忽视。     

Impact of vaccination against Haemophilus influenzae type b in Cuba]

OBJECTIVE: To assess the effectiveness of mass vaccination in Cuba of children under 2 years of age against Haemophilus influenzae type b (Hib), the most common causative pathogen of bacterial meningitis. METHODS: The availability of effective Hib conjugate vaccines led to a nationwide vaccination program in 1999 targeting all children under 2 years of age, with a 97% coverage rate achieved. To assess the program's impact, data from 1998 and 1999 from the National Bacterial Meningitis Reporting System were used. RESULTS: Vaccination efficacy was estimated at 99%. The overall incidence of Hib meningitis declined 46.1%, from 1.3 to 0.6 cases per 100,000 population. The greatest overall reduction, of 56.1%, occurred among children under 5 years of age. Among children under 1 year of age, the reduction was 70.5%, and among the rest of the age groups of children under 5, incidence decreased between 25.9% and 49.6%. In the group targeted for vaccination, incidence decreased 61.1%. Among children in the target group who contracted Hib meningitis, only 8 cases (24.2%) had been vaccinated, most with a single dose applied 1 month before becoming ill. CONCLUSIONS: Hib vaccination of all children under 2 years of age in Cuba greatly reduced the incidence of Hib meningitis, as measured by the National Bacterial Meningitis Reporting System.     

Profil bactériologique des méningites purulentes à l'hôpital d'enfants de Tunis

The therapeutic management of bacterial meningitis is still a matter for concern.Objective – The aim of this study was to analyze the profile of pathogens responsible for meningitis and their resistance to antibiotic drugs.Methods – Between January 1997 and December 1999, 114 strains were collected from CSF.Results – Streptococcus B and Escherichia coli were the most frequently identified pathogen found in neonatal meningitis. In children between three months and three years of age, Haemophilus Influenzae was the most frequently identified pathogen in meningitis (75%), followed by Streptococcus pneumoniae (22%). In children over three years of age, Streptococcus pneumoniae (57%) and Neisseria meningitidis (30%) were predominant. High levels of resistance were found: H. influenzae to ampicillin (33%) and S. pneumoniae to penicillin (56%). H. influenzae was more often isolated in meningitis in our study because of the absence of systematic vaccination in our country.Comments – The increasing prevalence of penicillin resistant S. pneumoniae strains isolated from meningitis make adequate therapeutic management difficult.     

Klebsiella meningitis in Taiwan: an overview.

Klebsiella infection has been considered to be an uncommon cause of meningitis. To determine its incidence and clinical features, we reviewed the microbiologic records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted between 1981 and 1995. Klebsiella meningitis was diagnosed in 79 patients with 83 episodes. All patients had klebsiella isolated from CSF and/or blood and typical symptoms and signs of acute bacterial meningitis. Of these, 74 were over 16 years of age and 2 of the 5 children were infants. There was an increased prevalence rate of klebsiella meningitis after 1986. Of the 83 episodes, only 9 occurred between 1981 and 1986, accounting for 7.8% of 115 cases with CSF and/or blood culture-proven acute bacterial meningitis, whereas in 1987-95, there were 74 episodes accounting for 17.7% of 419 bacteriologically proven cases. K. pneumoniae accounted for 69 episodes, K. oxytoca, 11 episodes and K. ozaenae, 3 episodes. Male gender, diabetes mellitus and liver cirrhosis were commonly associated with K. pneumoniae meningitis. Neurosurgical procedures were frequently associated with K. oxytoca meningitis. All three patients with K. ozaenae meningitis had a primary disease of the nasopharyngeal pathway. The mortality rate due to K. pneumoniae was 48.5%, K. oxytoca, 10% and K. ozaenae, 0%. In patients with K. pneumoniae meningitis, poor prognostic factors included age over 60 years, diabetes mellitus, bacteremia and severe neurological deficits on the first day of treatment.