Bacterial meningitis among children under the age of 2 years in a high human immunodeficiency virus prevalence area after Haemophilus influenzae type b vaccine introduction

Aim: The aim of this study was to describe bacterial causes of meningitis among children < 2 years in a high human immunodeficiency virus (HIV) prevalence area after introduction of routine Haemophilus influenzae type b vaccination. Methods: Data collected between April 2003 and December 2008 were extracted from a surveillance database and medical records of children < 2 years admitted in Mbarara Hospital, Uganda with suspected bacterial meningitis. HIV infection was confirmed using rapid tests and polymerase chain reaction and bacterial meningitis by using cerebrospinal fluid culture. Results: Between April 2003 and December 2008, 1464 children under 5 years were admitted with suspected bacterial meningitis of which 1235 (84.4%) had cerebrospinal fluid collected; 894 (72.4%) of these samples were from children < 2 years. Of the 894 samples, 64 (7.2%) grew an organism including Streptococcus pneumoniae (26; 41%), Salmonella species (20; 31%), H. influenzae (6; 9%) and coliforms (7; 11%), and five (8%) grew contaminants that are all coagulase negative Staphylococcus. Of the 894 children, 468 (52.3%) were tested for HIV; 16.7% were positive. Fifty‐one children had a pathogenic isolate and a treatment outcome, and 23 (45%) died; 13 (56.6%) deaths were due to S. pneumoniae, eight (34.8%) were due to Salmonella spp., one (4.3%) was due to H. influenzae and one (4.3%) was due to coliforms. HIV infection was associated with a threefold increase in mortality, increased likelihood of a bacterial isolate and decreased likelihood of malaria parasitaemia. Conclusion: Following H. influenzae type b vaccine introduction, S. pneumoniae and Salmonella spp. are the major causes of bacterial meningitis among children < 2 years in Uganda. Pneumococcal conjugate vaccines and reduction in mother to child transmission of HIV could reduce the observed mortality.     

Bacterial antigen detection test in meningitis

Objective : To evaluate the role of bacterial antigen detection test in cerebrospinal fluid (CSF) for a rapid etiological diagnosis of bacterial meningitis.Methods : The study included 36 cases of bacterial meningitis and 14 controls. Latex particle agglutination test (LPA test) for detection of bacterial antigen was done in the CSF using slidex meningitis kit (Biomeriux, France).Results : Using LPA test, an etiological diagnosis could be made in 83% cases of bacterial meningitis. In contrast, CSF Gram stain and culture showed 36% and 6% positivity, respectively. The sensitivity and specificity of LPA test were 83% and 100%, respectively. The common etiological organisms were S.pneumoniae, H. influenzae type b andN. meningitidis A. S. pneumoniae was encountered in all age groups whileH. influenzae type b was found only below one year of age.Conclusions : LPA test is a rapid and superior diagnostic tool as compared to CSF Gram stain and culture. The study recommends LPA test as an adjunct laboratory test for rapid etioiogical diagnosis of bacterial meningitis for prompt institution of proper antibiotics.     

Childhood bacterial meningitis in Pondicherry, South India

Objective: To identify causative bacteria from cerebrospinal fluid (CSF) of children with miningits and analyse various clinical and laboratory parameters.Methods: Over a 20 month period, September 1994 to April 1996, one hundred episodes of acute bacterial meningitis in children aged 1 month–12 years were studied in a tertiary urban hospital in South India. Organisms were isolated from the cerebrospinal fluid (CSF) in 35% of cases. Among infants and children, the two major pathogens wereH. influenzae (17%) andS.pneumoniae (12%).Results: The illness at presentation was mild in 13% and severe in 36% of cases. The association of subdural effusion in children with Salmonella Gp B meningitis merits attention. The overall case fatality rate was 25%.S.pneumoniae had a higher case fatality rate than Salmonella Gp B andH.influenzae (50% vs 17% vs 12%). All the three infants below 3 months of age withS.pneumoniae meningitis died. On analysis of selected clinical and laboratory features by discriminant analysis, CSF culture was the significant (P=0.02) variable in relation to outcome. In pneumococcal meningitis, CSF WBC count was a highly significant variable in relation to outcome (Wilk’s Lambda 0.15, F=24.64, P=0.0002).Conclusion: Prevention of infections due toH.influenzae andS.pneumoniae should be given higher priority.     

Dexamethasone and antibiotics for the empirical treatment of bacterial meningitis in Canadian children: A survey of paediatric infectious diseases specialists

PURPOSE:

With the changing epidemiology of the etiological agents causing bacterial meningitis in Canada, the purposes of this study were to determine what empirical antibiotic(s) is/are advocated, and whether dexamethasone is recommended as adjunctive therapy by paediatric infectious diseases specialists for suspected meningitis caused by Streptococcus pneumoniae, Neisseria meningitides, Haemophilus influenzae type b, and partially treated (PT) bacterial meningitis.

METHODS:

A questionnaire invoking the specialists’ preferred choices in treating bacterial meningitis was circulated by e-mail in March 1999 to 41 paediatric infectious diseases specialists or microbiologists (Paediatric Investigators Collaborative Network on Infections in Canada [PICNIC] members) who practised in 13 paediatric centres located in eight provinces.

RESULTS:

Thirty-two (78% response rate) replies were received by July 1999 from 11 paediatric centres in seven provinces. Dexamethasone was recommended by 11 of 32 (34%) respondents for suspected S pneumoniae, four of 32 (12%) for suspected N meningitides, 18 of 32 (56%) for suspected H influenzae type b and five of 32 (16%) for suspected PT meningitis. A trend for more frequent recommended use of dexamethasone for S pneumoniae, H influenzae type b and N meningitides meningitis was found in eastern provinces (Ontario, Quebec and Nova Scotia), as opposed to the western provinces (Manitoba, Saskatchewan, Alberta and British Columbia). The most commonly recommended first line empirical antibiotic therapy was vancomycin plus 3rd-generation cephalosporin (V+3C). This was recommended by 27 of 32 (84%) respondents for suspected S pneumoniae, seven of 32 (22%) for suspected N meningitides, six of 32 (19%) for suspected H influenzae type b and 24 of 32 (75%) for PT meningitis; the remainder recommended using a 3C empirically for each type of meningitis. The major reason cited by respondents for using V+3C for suspected S pneumoniae was the presence of high-and intermediate-level penicillin-resistant S pneumoniae in their centres. No differences were found in the choice of antibiotic(s) between practitioners in the eastern and western provinces.

CONCLUSIONS:

Although regional differences exist, the majority of paediatric infectious diseases experts no longer favour the use of dexamethasone for empirical therapy in most cases of bacterial meningitis. V+3C has become the regimen of choice in Canada for most cases of suspected bacterial meningitis.     

Latex agglutination test: An adjunct to the laboratory diagnosis of pyogenic bacterial meningitis

Gram stain, culture and latex agglutination test (LAT) of cerebrospinal flud were performed in 50 patients clinically diagnosed as suffering from pyogenic bacterial meningitus. Using all the three techniques, an aetiological diagnosis was made in 27 (54%).Neisseria meningitidis, Streptococcus pneumoniae and H. influenzae were the infecting organisms in 21 cases (44%). There were 12 additional cases in which LAT was the only clue to the diagnosis as compared to conventional techniques.Propionibacterium acnes was isolated from one case of anaerobic meningitis. It is concluded that LAT is an adjunct to conventional techniques in the diagnosis of pyogenic bacterial meningitis, where the latter tests fail.     

A retrospective epidemiological study of bacterial meningitis in an urban area in Belgium

In order to obtain epidemiological data on the incidence of bacterial meningitis (BM) before the systematic introduction of vaccination against Haemophilus influenzae type b, a retrospective study of 124 children with proven BM was performed in an urban area in Belgium. N. meningitidis was the most prevalent cause, followed by H. influenzae and S. pneumoniae. Over a period of 6 years the incidence of BM increased ten fold, mainly due to an increase in N. meningitidis. The median age of the children with BM was 17 months and 35% of those with H. influenzae were younger than 1 year. Significant risk factors for BM as a whole were: age under 1 year, male gender, non-Caucasian descent and winter time. These findings may have implications for future vaccination policy in Belgium. Conclusion Future vaccination schemes in Belgium should take into account that N. meningitis was the prevalent cause of bacterial meningitis and that certain factors increase the risk for developing bacterial meningitis. Received: 26 February 1996 / Accepted: 14 October 1996     

Haemophilus influenzae type D infection and JgG2 deficiency in a patient with chronic mucocutaneous candidiasis

A 14 year old boy with chronic mucocutaneous candidiasis and persistent pulmonary infection caused by Haemophylus influenzae and Streptococcus pneumoniae is reported. Initial bacterial culture studies showed H. influenzae type B and S. pneumoniae as causative agents. H. influenzae type D was constantly isolated from the patient's sputum. Abnormally low levels of serum immunoglobulin G2 (IgG2) found in the patient may have contributed to the pulmonary infection and H. influenzae type D may be an important causative agent in immunodeficient patients.     

Fatal meningitis due to multi-resistant Haemophilus influenzae type b

We report the case of a 3-month-old boy suffering from an acute bacterial meningitis due to a multi-resistant strain of Haemophilus influenzae type b. Also presented is our current strategy of treatment and chemoprophylaxis of Haemophilus influenzae meningitis in children.Abbreviation CSF cerebrospinal fluid     

Vaccine-preventable meningitis in French children with incorrect vaccination status from 2011 to 2013

The objective of this study was to determine the number of cases of pediatric meningitis or purpura fulminans associated with an incorrect vaccination status from 2011 to 2013 in France. A total of 48 children with vaccine-preventable meningitis or purpura fulminans, including three deaths, had an incorrect vaccination status: 26 cases were due to Neisseria meningitidis group C (54.2%), 19 to Streptococcus pneumoniae (39.6%), and three to Haemophilus influenzae type b (6.3%). The majority of patients (n = 35, 72.9%) had received no injection of the vaccine concerned. Over a 3-year period, 48 cases of bacterial meningitis or purpura fulminans in children could have been avoided if the French immunization schedule had been followed.     

Prolonged and secondary fever in childhood bacterial meningitis

In order to study the causes of prolonged and secondary fever in bacterial meningitis, a group of 102 infants and children with proven bacterial meningitis were studied. The causative agent wasHaemophilus influenzae in 58% of patients,Streptococcus pneumoniae in 25% andNeisseria meningitidis in 17%. Prolonged fever was observed in 12% of the patients. The established causes include, in order of frequency, subdural effusion, drug fever, otitis media, gastroenteritis and urinary tract infection. Secondary fever was noted in 18% of the patients. The causes, in order of frequency, were urinary tract infection, subdural effusion, otitis media, phlebitis, pneumonia and drug fever. Neither relapse of the meningitis nor inadequate response to antibiotic therapy was the cause for prolonged or secondary fever. Neurological sequalae were observed in 21 patients. There was no correlation between prolonged or secondary fever and neurological sequalae. We conclude that prolonged and secondary fever in patients with treated bacterial meningitis is rarely caused by the primary infection.     

Interleukin-8 levels in children with bacterial,tuberculous and aseptic meningitis

Objective : Interleukin-8 (IL-8) is produced in monocytes and vascular endothelial cells in response to stimulation with bacteria or lipopolysaccharides, and is released from these cells into blood stream or tissue fluid.Methods Cerebrospinal fluid (CSF) levels of interleukin-8 in 56 children with nonbacterial, bacterial and tuberculous meningitis (TBM), and in 15 control subjects were analyzed to evaluate the involvement of this cytokine in the pathogenesis acute bacterial meningitis and their discriminative value between different etiologies of meningitis. The kinetics of IL-8 concentrations during the course of bacterial meningitis was also evaluated in patients. IL-8 levels were significantly higher in bacterial and TBM than in aseptic meningitis and in control subjects (p<0.0001).Results: There was no difference in the levels of IL-8 between the non-bacterial meningitis and control groups. The analysis of the kinetics of production of IL-8 in patients with bacterial meningitis showed that the SSF concentrations of this cytokine decreased to undetectable values in recovery stage. Conversely in patients with TBM the concentrations of IL-8 were elevated in two weeks after beginning the specific treatment.Conclusion : The results suggest that determining IL-8 levels may be useful in the differential diagnosis.     

Fever as a sign of central nervous system infection

Over the past decade, there has been a variety of changes in the epidemiology and management of central nervous system (CNS) infection in children. With the rapid decline of invasive Haemophilus influenzae type b disease, Streptococcus pneumoniae is now the most prominent pathogen responsible for bacterial meningitis in children 1 to 23 months. The emergence of penicillin-resistant pneumococcal disease has led to the recommendation of empiric vancomycin and either ceftriaxone or cefotaxime for all children older than 1 month with probable or definite bacterial meningitis. Use of adjunctive dexamethasone therapy has proven beneficial in HIB meningitis and a beneficial effect I MS been suggested in pneumococcal meningitis. Fluid restriction as a routine to treat presumptive syndrome of inappropriate antidiuretic hormone in acute meningitis does not appear to improve outcome in hospitalized children. In addition, newly available diagnostic modalities allow more specific diagnosis and treatment of aseptic meningitis and encephalitis. This article reviews the three most common causes of CINS infection in the pediatric population which are meningitis, brain abscess, and encephalitis. Emphasis is placed on clinical features, diagnostic evaluation, and appropriate treatment of patients with suspected CNS infection. Early recognition and presumptive treatment of suspected CNS infection could limit neurological damage, exerting a positive impact on final outcome. Clinicians must he knowledgeable of emerging diseases, developing diagnostic trends, and new therapeutic options to provide quality patient care.     

The changing trend in the pattern of infective etiologies in childhood acute lower respiratory tract infection

The etiologic agents causing acute lower respiratory tract infection (LRTI) in hospitalized children were compared for 1995 and 1988. Between May 1994 to April 1995, 397 children were admitted to Tan Tock Seng Hospital for acute LRTI compared to 240 children in 1988. The following criteria for LRTI were used: (i) age less than 12 years with a community-acquired LRTI; (ii) presence of cough or fever of less than 2 weeks' duration; and (iii) presence of tachypnea, chest retractions or pulmonary infiltrates on chest X-ray. Sputum cultures were considered suitable for culture if there were less than 25 epithelial cells per low power field. Moraxella catarrhalis was considered only if heavy growth of more than 3+ was seen. Etiological agents were found in about 70% of patients in both studies. Viruses constituted 41.3% of the etiologic agents in 1995 but constituted only 28% in 1988; 36% had a bacterial etiology in 1995 compared to 15% in 1988. The most common bacteria in 1995 was M. catarrhalis (34.7%) followed by non-type B Haemophilus influenzae (33%). In contrast, in 1988, Mycoplasma (33%) was the predominant organism followed by H. influenzae (17%) and M. catarrhalis (11.4%). The increased incidence of M. catarrhalis could be due to antibiotic selection. A mixed viral-bacterial etiology was found in 12.3% of the 1995 cohort. The majority of the bacteria were positive by sputum cultures; only 4 (3.3%) had positive blood cultures. No penicillin resistance was detected in 1988; however, in 1995, penicillin resistance was found in 17% of the Streptococcus pneumoniae, 38.5% of H. influenzae and 83% of M. catarrhalis. It was also found that 30% of the S. pneumoniae were also resistant to erythromycin, and 23% were resistant to sulfamethoxaxole-trimethoprim; 5% of the H. influenzae had multiple resistance to erythromycin, sulfamethoxazole-trimethoprim and chloramphenicol. Among those patients with antibiotic resistance, 30% had received prior antibiotics of which 18% had had two or more antibiotics, frequently erythromycin or amoxycillin/ampicillin. Judicious use of antibiotics is required to check the rising trend of antibiotic resistance.     

In vitro antibiotic sensitivity pattern of common bacterial isolates from cases of acute bacterial meningitis with special reference to ceftriaxone

Ceftriaxone (RO 13-9904) has only recently been introduced in Benghazi and many parts of the word. We determined itsin vitro antibacterial activity against the primary aetiological agents of childhood meningitis in Benghazi, that included eighteen (23.3%) strains ofH. influenzas, 17 (22.1%) ofStr. pneumoniae and 1 (1.3%) ofN. meningitidis isolated from 77 cases of acute purulent meningitis above the age of neonatal period. All strains ofH. influenzae. Str. pneumoniae andN. meningitidis were sensitive to ceftriaxone and showed wide zones of inhibition by the disc diffusion technique of Kirby-Bauer. Ampicillin and chloramphenicol resistance was observed forH. influenzae (23% and 11% respectively), andStr. pneumoniae (12% and 0% respectively), in addition, 18% of strains ofStr. pneumoniae showed resistance to penicillin. The broad spectrum activity of ceftriaxone has been confirmed for our locality and this finding, together with its exceptionally long half-life, excellent penetration into the C.S.F. and ease of administration (single daily dose) warrants it as the drug of choice in empherical treatment of cases of acute bacterial meningitis in children in Benghazi and in cases where resistance to ampicillin and chloramphenicol are found on subsequent testing.     

细菌性脑膜炎的病原体及抗生素敏感性分析

目的　回顾分析我院 1 997～ 2 0 0 3年儿童细菌性脑膜炎 (菌脑 )的病原体及其抗生素敏感性。方法　分析符合菌脑临床诊断患儿脑脊液或血培养分离菌及其药敏试验结果。结果　菌脑 40 1例患儿中 97例细菌培养阳性 ,诊断阳性率 2 4 % ,最常见病原菌为金黄色葡萄球菌 (2 8% ) ,其次是肺炎链球菌 (1 9% )与大肠杆菌 (1 3 % ) ,并出现条件致病菌如微球菌。金黄色葡萄球菌分离株对青霉素不敏感 ,其中 1株对万古霉素与替考拉宁耐药 ;大肠杆菌、肠杆菌和假单胞菌均有对泰能的耐药株。结论　金黄色葡萄球菌是菌脑主要病原菌 ,临床用药须考虑当地的病原菌及其耐药问题。     

Penicillin and gentamicin therapyvs amoxicillin/clavulanate in severe hypoxemic pneumonia

Objective: To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.Methods: Children aged 2–59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO₂<90%) were included in the study. Patients with fever>10 days, bacterial meningitis, prior antibiotic therapy >24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups—Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly.Results: 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated wereS. pneumoniae (n=3) andH. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistantH. influenzae-b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76±25 hrs and group B was 75±24 hrs (p>0.1).Conclusion: In children of 2–59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.     

Bacterial meningitis in older children

A review was performed of 25 cases of bacterial meningitis in previously healthy children aged 6 years or older during a 10-year period. The rate of infection in this age group relative to all cases of pediatric bacterial meningitis was 4%. Pathogens included Haemophilus influenzae type b in 10 cases (40%), Neisseria meningitidis in 9 cases (36%), and Streptococcus pneumoniae in 6 cases (24%). Physical findings revealed 21 patients (84%) with some degree of altered consciousness and 25 patients (100%) with nuchal rigidity. In all instances, the cerebrospinal fluid exhibited pleocytosis with a predominance of polymorphonuclear leukocytes. Eleven patients (44%) were afebrile on presentation. Of 22 surviving patients, 10 (45%) were afebrile without subsequent fever after administration of the initial dose of antibiotics, in 5 (23%) fever resolved within 24 hours, and in 6 (27%) fever resolved within 48 hours of treatment; there was no instance of prolonged or secondary fever noted. Death occurred in 3 cases (12%). Bacterial meningitis is uncommon in older children. As compared with younger children, older children with bacterial meningitis commonly present without fever and tend to have their fever resolve shortly after effective antibiotic therapy is initiated without manifesting prolonged or secondary fever patterns. Haemophilus influenzae type b is a common cause of bacterial meningitis in children aged 6 years or older; empirical antibiotic therapy in this clinical situation should include treatment of this pathogen.     

The Present Status of Sepsis of Children and Its Chemotherapy in Japan

The present status of etiology and chemotherapy of sepsis of children in Japan is reported. In newborns and infants less than 3 months of age, the most common pathogens in sepsis and purulent meningitis are Escherichia coli and group B Streptococci, although Staphylococcus aureus becomes the second most important bacteremic pathogen after the 3rd day of life. In order infants and children, S. aureus, Haemophilus influenzae and Streptococcus pneumoniae are the most common bacteremic pathogens. Listeriosis is increasing in Japan, yet is responsible for only 1.4% of cases of purulent meningitis and 0.5% of sepsis in children at present. The chemotherapy of sepsis and purulent meningitis has been changed from the old standard ampicillin therapy (with gentamicin in neonates) to mono-therapy with a new cephem, especially cefotaxime in Japan, since over 50% of strains of E. coli are already resistant to ampicillin.     

Folgen der bakteriellen Meningitis

The frequency of residual neurological abnormalities after bacterial meningitis in children is about 10–30%. Long-term sequelae include hearing deficits (7–19%), epilepsy (4–7%), mental retardation (10–15%), neuropsychological deficits, behaviour problems, severe (2–10%) and subtle motor abnormalities, cranial nerve paresis (2–7%), visual impairment (2–4%) and hydrocephalus (1–2%). Neonates have a higher risk of neurological sequelae after meningitis than older children, especially when it is caused by gram-negative enteric bacilli. After tuberculous meningitis 40–90% of the children have neurological deficits, depending on the stage. Risk factors for neurological sequelae are young age, type of pathogen (tuberculosis, group B streptococci, gram-negative enteric bacilli, and pneumococci are associated with worse outcome than H. influenzae and meningococci), delay in the start of antimicrobial treatment, acute neurological symptoms, and low glucose level, high number of bacteria and high intensity of host inflammatory response in the cerebrospinal fluid (marked rise in levels of tumour necrosis factor, interleukin-1, prostaglandins). After recovery early hearing evaluation and careful follow-up are required for full assessment of any sequelae.