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1.  Prospective surveillance of neonatal meningitis. 
Archives of Disease in Childhood  1993;69(1 Spec No):14-18.
Neonatal meningitis is a serious problem with a high mortality and frequent neurological sequelae. The incidence of neonatal meningitis was calculated and the aetiology, clinical and laboratory features, and the treatment of cases recorded prospectively over a 7 year 8 month period was documented. It was further investigated whether secondary meningitis had occurred after lumbar puncture. The estimated incidence of bacterial, viral, and fungal meningitis was 0.25, 0.11, and 0.02 per 1000 live births respectively. There were eight cases of early onset meningitis (seven definite, one probable) and group B streptococci accounted for six (75%) of these. Blood cultures were negative in only one of seven cases of definite early bacterial meningitis. Of the 15 late onset cases, Gram negative organisms accounted for six of the seven bacterial cases. The overall mortality was 26%. Of the 11 survivors of bacterial meningitis, three (27%) had significant neurological sequelae at follow up (between three months to three years later). As in the first 48 hours after birth an initial blood culture is unlikely to be negative if bacterial meningitis is present, lumbar puncture can be deferred if the procedure might exacerbate respiratory distress. Although approximately 1880 infants had a lumbar puncture during the review period, only one case of meningitis was found where it was possible that lumbar puncture in a bacteraemic infant may have caused meningeal infection. The incidence of this potential complication must therefore be low.
PMCID: PMC1029390  PMID: 8346945
2.  Cerebro Spinal Fluid Analysis in Childhood Bacterial Meningitis 
Oman Medical Journal  2008;23(1):32-33.
The aim of this study was to analyze the lumbar puncture of all suspected cerebrospinal fluid (CSF) for suspected meningitis.
This study was undertaken in the department of Child Health, the Royal Hospital. The details of CSF of all files of the children who had undergone lumbar puncture for suspected meningitis from January 1, 2004 to December 31, 2004; were enrolled for the study.
A total of 395 lumbar punctures were done to exclude bacterial meningitis. Out of the 142 CSF studies in neonates, 17 (12%) had the cytology suggestive of bacterial meningitis and 15 (88%) of them being culture positive. The commonest pathogen was Group B Streptococcus (70%).The bacterial antigens were positive only in 41% of the confirmed cases of bacterial meningitis, all being that of Group B Streptococcus and gram stain positivity in 45 percent of cases. In the 1- 3 months group all the 17 lumbar punctures were normal. Of the 179 lumbar punctures done in 3-18 months group, only 11(6%) were abnormal, 72% being culture positive. Streptococcus pneumonia was the commonest organism (88%). Bacterial antigens were positive only in 2 of the 8 culture positive cases where gram stain was positive in 4 out of 8 cases. Irritability, lethargy and sick looking appearance were present in all the positive cases. None of the 28 children from 18 months to 5 years had abnormal CSF or positive CSF culture.
Based on the fact that only 7% of the 395 CSF studies were abnormal, we conclude that better clinical judgment and diagnostic criteria are warranted, before laying out guidelines for lumbar puncture to confirm or exclude the diagnosis of bacterial meningitis. Besides fever and convulsions as indicators for CSF studies clinical parameters such as irritability, lethargy and sick looking appearance are better indicators.
PMCID: PMC3338990  PMID: 22567207
3.  The Association of Meningitis with Postoperative Cerebrospinal Fluid Fistula 
Objective To determine the risk factors for and the clinical course of postoperative meningitis following lateral skull base surgery and to determine its relationship to cerebrospinal fluid (CSF) fistula.
Patients Patients undergoing lateral skull base surgery between July 1999 and February 2010 at an academic tertiary referral center. All subjects had culture-proven meningitis or suspected bacterial meningitis in the postoperative period. Medical records were compared with the lateral skull base patients who did not develop meningitis.
Results Of 508 procedures, 16 patients developed meningitis (3.1%). The most common diagnosis was acoustic neuroma in 81.3%; 68.8% of patients had a CSF leak prior to onset of meningitis, and 50% received a lumbar drain. The median time from surgery to the onset of meningitis was 12 days with a range of 2 to 880 days. The relative risk of developing meningitis in the setting of postoperative CSF fistula is 10.2 (p < 0.0001). No meningitis-associated mortality was observed.
Conclusions Postoperative meningitis occurred in a small number of patients undergoing lateral skull base surgery. A postoperative CSF fistula leads to an increased risk of meningitis by a factor of 10.2.
PMCID: PMC3578594  PMID: 24294557
meningitis; postoperative meningitis; acoustic neuroma
4.  Evaluation of IL-6 and High Sensitive C Reactive Protein Value in CSF and Serum Children Suspected Meningitis Referred to Pediatric Emergency Room 
Acute bacterial meningitis which is a pediatric emergency with high mortality and morbidity must be diagnosed and treat promptly. Often diagnosis of bacterial meningitis from viral meningitis is difficult after some days. Determination of some inflammatory mediators’ example IL-6 and HS-CRP were useful in differential diagnosis of bacterial and viral meningitis.
This study attempted to Determining HS-CRP and IL6 in serum and CSF in children suspected meningitis and Comparing value HS-CRP and IL6 in bacterial/viral meningitis.
Patients and Methods
Of children that hospitalized in pediatric emergency ward (Ghaem Hospital Mashhad university of medical science, in duration 01 Dec 2010-01 Dec 2011) and for they performed lumbar puncture, 1cc serum and CSF of they were taken to laboratory and have measured IL-6 with Elisa method and HS-CRP with immunoturbidometry method, patients were followed up and finally we compared levels of this two mediators.
Finally, this study performed on 81 children and infants. From 81 cases, 27 cases (33.3%) had bacterial meningitis 27 cases (33.3%) viral meningitis and 27 cases (33.3%) had normal CSF. IL-6 concentration in the CSF and serum were significantly raised in cases of bacterial meningitis (P = 0.001, P = 0.01) but HS-CRP concentration in the CSF and serum were not significantly raised in cases of bacterial meningitis (P = 0.46, P = 0.29). Mean IL-6 concentration in the CSF in bacterial meningitis was (180.74) and in viral meningitis was (39.08) .Mean HS-CRP in CSF in bacterial meningitis was (2.22) and viral meningitis was (1.29). Mean HS-CRP in serum in bacterial meningitis was (8.23) and viral meningitis was (6.36).
The measurement of IL-6 in the CSF and serum in potentially a very useful diagnostic tool for differential diagnosis of bacterial and viral meningitis.
PMCID: PMC3587874  PMID: 23483792
Interleukin-6; Meningitis; Child
5.  Bacterial Meningitis in Malawian Adults, Adolescents, and Children During the Era of Antiretroviral Scale-up and Haemophilus influenzae Type b Vaccination, 2000–2012 
Culture positive bacterial meningitis has fallen over a 12-year period in urban Malawi following Hib vaccination. Hib, NTS, and pneumococcal meningitis have fallen significantly in children. Pneumococcal meningitis has not fallen in adults; NTS and pneumococcal meningitis are seasonal.
Background. We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART).
Methods. We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012.
Results. There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio [IRR], 0.93; 95% CI, .92–.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85–.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97–1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100 000 cases in children aged <14 years, 6 per 100 000 adolescents, and 10 per 100 000 adults.
Conclusions. Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic “meningitis belt” in Africa is essential.
PMCID: PMC4001285  PMID: 24496208
meningitis; Africa; HIV; vaccination; antiretroviral therapy
6.  Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis 
Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia.
This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed.
The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n = 7, 71%–100%), other Klebsiella species (n = 7, 28%–80%), and Staphylococcus (n = 36, 25%–40%).
The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance.
PMCID: PMC3987067  PMID: 24764539
Celebrospinal fluid; Antimicrobial resistance; Culture and sensitivity; Empiric therapy; Meningitis; Namibia
7.  Antimicrobial Susceptibility of Bacteria Isolated from Cerebrospinal Fluids in an Iranian Referral Pediatric Center, 1998-2008 
Mædica  2012;7(2):131-137.
Antimicrobial susceptibility patterns of bacterial meningitis provide essential information regarding selection of antibiotic therapy for patients with bacterial meningitis. This study presents data on causes of bacterial meningitis and their susceptibility pattern among children at Children's Medical Center (CMC), a referral tertiary care center in Iran. In this comprehensive retrospective study we reviewed microbiology records of all inpatients suspected to bacterial meningitis, during 1998-2008 of period. Of 11269 CSF cultures examined in the study, 329 (2.9%) were positive for bacterial growth. Overall, coagulase negative staphylococci (CONS) were the most frequent group of organism recovered from our CSF cultures (40%), followed by gram negative enteric bacilli (19.7%). Also, high rates of oxacillin and vancomycin resistance were found among staphylococci. In our study more than 80% of gram-negative enteric bacteria were resistant to ampicillin; we also found high rates of cephalosporin resistance among these organisms. Over 55% of S. pneumoniae were resistant to penicillin. Staphylococci species and gram-negative enteric organisms were the most common pathogens isolated from CSF cultures in this study. It seems that nosocomial meningitis is the main cause of bacterial meningitis in CMC Hospital. Our report draws attention to the importance devising a national strategy to control the spread of resistance in Iran.
PMCID: PMC3557420  PMID: 23399784
bacterial meningitis; antimicrobial susceptibility; CSF
8.  Spatial Dynamics of Meningococcal Meningitis in Niger: observed patterns in comparison with measles 
Epidemiology and infection  2011;140(8):10.1017/S0950268811002032.
Throughout the African meningitis belt, meningococcal meningitis outbreaks occur only during the dry season. Measles in Niger exhibits similar seasonality, where increased population density during the dry season likely escalates measles transmission. Because meningococcal meningitis and measles are both directly transmitted, we propose that host aggregation also impacts the transmission of meningococcal meningitis. Although climate affects broad meningococcal meningitis seasonality, we focus on the less examined role of human density at a finer spatial scale. By analysing spatial patterns of suspected cases of meningococcal meningitis, we show fewer absences of suspected cases in districts along primary roads, similar to measles fadeouts in the same Nigerien metapopulation. We further show that, following periods during no suspected cases, districts with high reappearance rates of meningococcal meningitis also have high measles reintroduction rates. Despite many biological and epidemiological differences, similar seasonal and spatial patterns emerge from the dynamics of both diseases. This analysis enhances our understanding of spatial patterns and disease transmission and suggests hotspots for infection and potential target areas for meningococcal meningitis surveillance and intervention.
PMCID: PMC3846174  PMID: 22009033
9.  Analysis of bacterial isolates from cerebrospinal fluid. 
Journal of Clinical Microbiology  1984;19(2):144-146.
We set out to determine the frequency of occurrence of contamination of cerebrospinal fluid with bacteria, seeking also to identify aids to differentiating contaminants from etiologically significant isolates. From 2,091 specimens, 182 bacterial isolates were obtained from 129 patients. Meningitis was the source of 81 isolates (32 patients); contamination yielded 101 isolates (97 patients). The cell counts and protein and glucose concentrations in the cerebrospinal fluid were significantly more often abnormal in specimens from patients with meningitis. Haemophilus influenzae and enteric gram-negative bacilli were usually cause for meningitis, whereas Staphylococcus epidermidis was the most common contaminant. In view of the reported high rate of procedural error in carrying out lumbar puncture, a program aimed at teaching proper technique is recommended to decrease the frequency of false-positive cultures of cerebrospinal fluid.
PMCID: PMC271004  PMID: 6699142
10.  The causative organisms of bacterial meningitis in Korean children, 1986-1995. 
Bacterial meningitis remains a serious cause of morbidity and mortality in childhood. Epidemiologic investigations have shown variability in disease risks among different populations and races. In Korea, however, basic epidemiologic information on bacterial meningitis in children is limited. The main purpose of this study was to analyze bacteriologically proven meningitis cases in terms of the relative frequency of causative organisms, mortality rate, and age distribution beyond the neonatal period. Data was obtained from the hospital records who had been diagnosed with bacterial meningitis at 13 general or university hospitals from 1986 through 1995. The patients had at least one positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5 years cumulatively. Streptococcus pneumoniae was the most common bacteria responsible for 48 (35.0%) of all cases regardless of age, followed by Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%) patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis, S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common organisms of culture-proven bacterial meningitis in the last 10 years have been S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further study should be extended to nation-wide epidemiologic evaluation to show the incidence of bacterial meningitis caused by these three important organisms.
PMCID: PMC3054337  PMID: 9539321
11.  Group-A-streptococcal meningitis in a 7-year-old child – a rare pathogen in a non-immune compromised patient 
BMJ Case Reports  2011;2011:bcr1020114896.
A case is presented of meningitis in a 7-year-old female child caused by Group A streptococcus (GAS), a rare bacterial cause of meningitis, with a high rate of morbidity (46%) and mortality (10%). GAS is susceptible for empiric antibiotic therapy aimed at the most prevalent pathogens of meningitis. As GAS meningitis is typically associated with ear-nose-throat (ENT) infections, specific search for a reservoir is advised. Bacterial typification often demonstrates M-protein gene sequence type (EMM type) 1.0 associated with upper respiratory tract infections and also severe, invasive GAS infections. Follow-up investigation including neurologic developmental status and audiologic testing is necessary. Although GAS is a very uncommon cause of acute bacterial meningitis in children, high morbidity and mortality have been reported. Being associated with ENT infections, a search for a GAS reservoir is proposed. GASs are susceptible for common empiric antibiotic therapies in meningitis. Follow-up investigation is necessary.
PMCID: PMC3229411  PMID: 22674699
12.  Bacterial Meningitis in Malawian Infants <2 Months of Age 
Supplemental Digital Content is available in the text.
Neonatal meningitis is an important cause of morbidity in sub-Saharan Africa and requires urgent empiric treatment with parenteral administered antibiotics. Here we describe the etiology, antimicrobial susceptibility and suitability of the World Health Organization first-line recommended antibiotics (penicillin and gentamicin) for bacterial meningitis in young infants in Malawi.
We reviewed all cerebrospinal fluid samples received from infants ≤2 months of age with clinically suspected meningitis between January 1, 2002, and December 31, 2008, at the Queen Elizabeth Central Hospital in Blantyre, Malawi.
We identified 259 culture-positive isolates from 259 infants ≤2 months of age. Sixty isolates were from neonates ≤7 days old, in whom the most common pathogens were Group B Streptococcus (27/60; 45.0%), Streptococcus pneumoniae (13/60; 21.7%) and nontyphoidal Salmonella enterica (7/60; 11.7%). One hundred and ninety one isolates were from young infants who were >7 days and ≤2 months of age. In this group, the most common isolates were S. pneumoniae (80/191; 41.9%), Group B Streptococcus (38/191; 19.9%) and nontyphoidal Salmonella enterica (34/191; 17.8%). More isolates were susceptible to ceftriaxone than to the combination of penicillin and gentamicin (218/220; 99.1% vs. 202/220; 91.8%, Fisher’s exact test P = 0.006). In particular, Gram-negative isolates were significantly more susceptible to ceftriaxone than to gentamicin (72/74; 97.3% vs. 63/74; 85.1%, Fisher’s exact test P = 0.020). Penicillin and gentamicin provided less coverage for Gram-negative than Gram-positive isolates (74/86; 86.0% vs. 155/163; 95.1%, χ2 = 6.24, P = 0.012).
In view of these results, the World Health Organization recommendations for empiric penicillin and gentamicin for suspected neonatal meningitis should be reevaluated.
PMCID: PMC4025590  PMID: 24378940
newborn; infant; meningitis; drug resistance; microbial; Africa
13.  Postoperative meningitis after spinal surgery: a review of 21 cases from 20,178 patients 
BMC Infectious Diseases  2014;14:220.
Postoperative bacterial meningitis is a rare complication of spinal surgery and is considered to be a complication related to intraoperative incidental durotomy. A high index of suspicion for meningitis is essential in patients who have the clinical triad of fever, neck stiffness and consciousness disturbance during the postoperative period. A delay in diagnosis or treatment can lead to morbidity and mortality. Due to the low incidence of postoperative meningitis, very few studies have reported this complication. The purpose of this study was to report the clinical features, laboratory evaluations, treatment course and prognosis of 21 patients with post spinal surgery meningitis.
We retrospectively reviewed 21 patients (13 male, 8 female) with the diagnosis of postoperative meningitis after lumbar spinal surgery between January 2001 and Aug 2011. The median age of the patients was 67 years old (range 27 to 82 years) at the time of surgery. We recorded the preoperative diagnosis, operative methods, amount of drainage, clinical manifestations, laboratory evaluations, cerebrospinal fluid study, and infectious organisms. All patients diagnosed with postoperative meningitis received at least two weeks of antibiotic treatment. Clinical outcomes were assessed after at least two years of follow-up.
From January 2001 to August 2011, 20,178 spinal operations were performed in our institution, and 21 patients (0.10%) were diagnosed with postoperative meningitis. Eighteen patients (85.7%) had fever, 19 (90.5%) had neck stiffness, and 16 (76.2%) had consciousness disturbance. All patients had at least two of the classic triad. In addition, 9 patients (42.9%) had headache, 3 (14.3%) had focal neurological deficits, and 2 (9.5%) had seizure attacks. There was no mortality in this series. Postoperative meningitis showed no adverse effect on the results of spinal surgery after follow-up for at least two years.
Postoperative meningitis is a rare complication after spinal lumbar surgery. A high index of suspicion for meningitis should be maintained in patients with the clinical triad of fever, neck stiffness, and consciousness disturbance after spinal surgery. Intraoperative incidental durotomy is the most important predictor. An early diagnosis and appropriate antibiotic treatment can lead to a good outcome.
PMCID: PMC4013809  PMID: 24755138
Post spinal surgery; Postoperative meningitis; Complications
14.  Aetiology, Clinical Presentation, and Outcome of Meningitis in Patients Coinfected with Human Immunodeficiency Virus and Tuberculosis 
AIDS Research and Treatment  2011;2011:180352.
We conducted a retrospective review of confirmed HIV-TB coinfected patients previously enrolled as part of the SAPiT study in Durban, South Africa. Patients with suspected meningitis were included in this case series. From 642 individuals, 14 episodes of meningitis in 10 patients were identified. For 8 patients, this episode of meningitis was the AIDS defining illness, with cryptococcus (9/14 episodes) and tuberculosis (3/14 episodes) as the commonest aetiological agents. The combination of headache and neck stiffness (78.6%) was the most frequent clinical presentation. Relapsing cryptococcal meningitis occurred in 3/7 patients. Mortality was 70% (7/10), with 4 deaths directly due to meningitis. In an HIV TB endemic region we identified cryptococcus followed by tuberculosis as the leading causes of meningitis. We highlight the occurrence of tuberculous meningitis in patients already receiving antituberculous therapy. The development of meningitis heralded poor outcomes, high mortality, and relapsing meningitis despite ART.
PMCID: PMC3246294  PMID: 22216407
15.  Serum Procalcitonin in Viral and Bacterial Meningitis 
In children with meningitis, there is a difficulty to verify the etiology as viral or bacterial. Therefore, intensive research has been carried out to find new and rapid diagnostic methods for differentiating bacterial from viral meningitis.
The aim of this work was to study the behavior of procalcitonin (PCT) and whether it can be used to differentiate children with bacterial from those with viral meningitis. We also compared PCT to C-reactive protein (CRP) and white blood cell count.
Patients and Methods:
Forty children aged from 4 months to 12 years with clinically suspected meningitis were studied. Lumbar punctures were done for all cases before starting initial antibiotic treatment. According to the results of bacterial cultures and cerebrospinal fluid (CSF) cytochemical profile, our patients were classified into two groups: bacterial meningitis group and viral meningitis group. PCT, CRP, and leukocyte count were measured at the time of admission and after 3 days.
Forty children aged from 4 months to 12 years with clinically suspected meningitis were studied. Lumbar punctures were done for all cases before starting initial antibiotic treatment. According to the results of bacterial cultures and cerebrospinal fluid (CSF) cytochemical profile, our patients were classified into two groups: bacterial meningitis group and viral meningitis group. PCT, CRP, and leukocyte count were measured at the time of admission and after 3 days.
PCT levels were significantly higher in patients with bacterial meningitis (mean, 24.8 ng/ml) compared to patients with viral meningitis (mean, 0.3 ng/ml) (P<0.001). PCT levels in bacterial meningitis group decreased after 3 days of starting treatment, but remained higher than viral meningitis group (mean, 10.5 ng/ml). All CSF parameters, blood leukocytes, and CRP showed overlapping values between the two groups. Serum PCT with cut off value >2 ng/ml showed sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 66%, 68%, and 100%, respectively, for the diagnosis of bacterial meningitis.
Serum procalcitonin level has a better diagnostic and prognostic value than CRP or leukocyte count to distinguish between bacterial and viral meningitis. It is also a good indicator of the efficacy of treatment of bacterial meningitis.
PMCID: PMC3068572  PMID: 21572603
C-reactive protein; Meningitis; Procalcitonin
16.  Significant sequelae after bacterial meningitis in Niger: a cohort study 
BMC Infectious Diseases  2013;13:228.
Beside high mortality, acute bacterial meningitis may lead to a high frequency of neuropsychological sequelae. The Sahelian countries belonging to the meningitis belt experience approximately 50% of the meningitis cases occurring in the world. Studies in Africa have shown that N. meningitidis could cause hearing loss in up to 30% of the cases, exceeding sometimes measles. The situation is similar in Niger which experiences yearly meningitis epidemics and where rehabilitation wards are rare and hearing aids remain unaffordable. The aim of this study was to estimate the frequency of neuropsychological sequelae after acute bacterial meningitis in four of the eight regions of Niger.
Subjects exposed to acute bacterial meningitis were enrolled into a cohort with non exposed subjects matched on age and gender. Consenting subjects were interviewed during inclusion and at a control visit two months later. If clinical symptoms or psychological troubles persisted at both visits among the exposed subjects with a frequency significantly greater than that observed among the non exposed subjects, a sequelae was retained. The comparison of the frequency of sequelae between non exposed and exposed subjects to bacterial meningitis was also calculated using the Fisher exact test.
Three persisting functional symptoms were registered: headaches, asthenia, and vertigo among 31.3, 36.9, and 22.4% respectively of the exposed subjects. A significant motor impairment was retrieved among 12.3% of the exposed versus 1.6% of the non exposed subjects. Hearing loss significantly disabled 31.3% of the exposed subjects and 10.4% exhibited a serious deafness.
This study carried out in Niger confirms two serious neurological sequelae occurring at high frequencies after bacterial meningitis: severe and profound hearing loss and motor impairment. Cochlear implantation and hearing aids are too expensive for populations living in developing countries. Neurological sequelae occurring after meningitis should sensitize African public health authorities on the development of rehabilitation centers. All these challenges can be met through existing strategies and guidelines.
PMCID: PMC3664072  PMID: 23687976
Meningococcal; Complications; Disability; Less-developed countries
17.  The emergence of resistant pneumococcal meningitis—implications for empiric therapy 
Archives of Disease in Childhood  2002;87(3):207-210.
Background: Following the emergence of penicillin and cephalosporin resistant pneumococcal meningitis in the United States, inclusion of vancomycin in empiric therapy for all suspected bacterial meningitis was recommended by the American Academy of Pediatrics. Few data are available to evaluate this policy.
Aims: To examine the management and clinical course in relation to antibiotic therapy of a large unselected cohort of children with pneumococcal meningitis in a geographic area where antibiotic resistance has recently increased.
Methods: Retrospective review of all cases of pneumococcal meningitis in a defined population (Sydney, Australia), 1994–99.
Results: A total of 104 cases without predisposing illnesses were identified; timing of lumbar puncture (LP) was known in 103. Resistance to penicillin increased from 0 to 20% over the study period. Only 57 (55%) had an early LP (prior to parenteral antibiotics); 55 (96%) had organisms on Gram stain. Severe disease (intensive care admission or death) increased significantly from 57 cases with early LP (28%) to 33 with delayed LP (42%) to 13 with no LP (62%). Evidence of pneumococcal infection was available within 24 hours in 85% of those with delayed or no LP. Outcome was not related to empiric vancomycin use, which increased from 5% prior to 1998 to 48% in 1999.
Conclusion: LP is frequently delayed in pneumococcal meningitis. Based on disease severity, empiric vancomycin is most justified when LP is deferred. If an early LP is done, vancomycin can be withheld if Gram positive diplococci are not seen.
PMCID: PMC1719212  PMID: 12193427
18.  Cerebrospinal fluid pressure in pyogenic meningitis. 
Archives of Disease in Childhood  1989;64(6):814-820.
The pressure of cerebrospinal fluid taken at lumbar puncture was recorded objectively by strain gauge pressure measurement in 35 infants and children with pyogenic meningitis. Raised pressures were found in 33 children. The median pressure was 15 mm Hg (range 4-70 mm Hg) in all age groups. The pressure level varied throughout the infection, but a higher median pressure (19 mm Hg) was found when this was measured on the day of admission. The clinical features of the meningitis in these patients suggest that many of the presenting symptoms and signs are those of pressure. These results show that high pressure is frequently present in childhood meningitis, not just in those who die from cones or who have radiological evidence of hydrocephalus. We conclude that raised cerebrospinal fluid pressure is a frequent accompaniment of childhood meningitis and may need treatment in its own right and is therefore one further important factor influencing the course and outcome of childhood meningitis.
PMCID: PMC1792580  PMID: 2673052
19.  Presentation and Outcome of Tuberculous Meningitis in a High HIV Prevalence Setting 
PLoS ONE  2011;6(5):e20077.
Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM.
A retrospective review of cerebrospinal fluid findings and clinical records over a six-month period (March 2009–August 2009). Definite, probable and possible TBM were diagnosed according to published case definitions.
TBM was diagnosed in 120/211 patients (57%) with meningitis. In 106 HIV-infected patients with TBM, six-month all-cause mortality was lower in those who received antiretroviral therapy (ART) during TB treatment; hazard ratio = 0.30 (95% CI = 0.08–0.82). Factors associated with inpatient mortality in HIV-infected patients were 1) low CD4+ count at presentation; adjusted odds ratio (AOR) = 1.4 (95% confidence interval [CI] = 1.03–1.96) per 50 cells/µL drop in CD4+ count and, 2) higher British Medical Research Council TBM disease grade (2 or 3 versus 1); AOR = 4.8 (95% CI = 1.45–15.87).
Starting ART prior to or during TB treatment may be associated with lower mortality in patients with HIV-associated TBM. Advanced HIV and worse stage of TBM disease predict in-hospital mortality in patients presenting with TBM.
PMCID: PMC3098272  PMID: 21625509
20.  Hospital Surveillance of Childhood Bacterial Meningitis in Senegal and the Introduction of Haemophilus influenzae Type b Conjugate Vaccine 
Bacterial meningitis is an important cause of morbidity and mortality in children living in low-resource settings. Pediatric bacterial meningitis cases < 5 years of age were identified through a regional hospital surveillance system for 3 years after introduction of routine immunization with Haemophilus influenzae type b (Hib) conjugate vaccine in Senegal in July 2005. Cases from the national pediatric hospital were also tracked from 2002 to 2008. The regional surveillance system recorded 1,711 suspected pediatric bacterial meningitis cases. Of 214 laboratory-confirmed cases, 108 (50%) were caused by Streptococcus pneumoniae, 42 (20%) to Hib, and 13 (6%) to Neisseria meningitidis. There was a 98% reduction in the number of hospitalized Hib meningitis cases from Dakar Region in 2008 compared with 2002. The surveillance system provides important information to the Ministry of Health as they consider self-funding Hib vaccine and introducing pneumococcal vaccine.
PMCID: PMC2990054  PMID: 21118944
21.  Sequelae due to bacterial meningitis among African children: a systematic literature review 
BMC Medicine  2009;7:47.
African children have some of the highest rates of bacterial meningitis in the world. Bacterial meningitis in Africa is associated with high case fatality and frequent neuropsychological sequelae. The objective of this study is to present a comprehensive review of data on bacterial meningitis sequelae in children from the African continent.
We conducted a systematic literature search to identify studies from Africa focusing on children aged between 1 month to 15 years with laboratory-confirmed bacterial meningitis. We extracted data on neuropsychological sequelae (hearing loss, vision loss, cognitive delay, speech/language disorder, behavioural problems, motor delay/impairment, and seizures) and mortality, by pathogen.
A total of 37 articles were included in the final analysis representing 21 African countries and 6,029 children with confirmed meningitis. In these studies, nearly one fifth of bacterial meningitis survivors experienced in-hospital sequelae (median = 18%, interquartile range (IQR) = 13% to 27%). About a quarter of children surviving pneumococcal meningitis and Haemophilus influenzae type b (Hib) meningitis had neuropsychological sequelae by the time of hospital discharge, a risk higher than in meningococcal meningitis cases (median = 7%). The highest in-hospital case fatality ratios observed were for pneumococcal meningitis (median = 35%) and Hib meningitis (median = 25%) compared to meningococcal meningitis (median = 4%). The 10 post-discharge studies of children surviving bacterial meningitis were of varying quality. In these studies, 10% of children followed-up post discharge died (range = 0% to 18%) and a quarter of survivors had neuropsychological sequelae (range = 3% to 47%) during an average follow-up period of 3 to 60 months.
Bacterial meningitis in Africa is associated with high mortality and risk of neuropsychological sequelae. Pneumococcal and Hib meningitis kill approximately one third of affected children and cause clinically evident sequelae in a quarter of survivors prior to hospital discharge. The three leading causes of bacterial meningitis are vaccine preventable, and routine use of conjugate vaccines could provide substantial health and economic benefits through the prevention of childhood meningitis cases, deaths and disability.
PMCID: PMC2759956  PMID: 19751516
22.  African meningitis belt pneumococcal disease epidemiology indicates a need for an effective serotype 1 containing vaccine, including for older children and adults 
Pneumococcal conjugate vaccine strategies in GAVI-eligible countries are focusing on infant immunization but this strategy may not be optimal in all settings. We aimed to collect all available population based data on pneumococcal meningitis throughout life in the African meningitis belt and then to model overall meningitis risk to help inform vaccine policy.
After a systematic review of literature published from 1970 through the present, we found robust population-based Streptococcus pneumoniae (Sp) meningitis data across age strata for four African meningitis belt countries that included 35 surveillance years spanning from 1970 to 2005. Using these data we modeled disease risk for a hypothetical cohort of 100,000 persons followed throughout life.
Similar to meningococcal meningitis, laboratory-confirmed pneumococcal meningitis was seasonal, occurring primarily in the dry season. The mean annual Sp meningitis incidence rates were 98, 7.8 to 14, and 5.8 to 12 per 100,000 among persons <1, 1 through 19, and 20 to 99 years of age, respectively, which (in the absence of major epidemics) were higher than meningococcal meningitis incidences for persons less than 1 and over 20 years of age. Mean Sp meningitis case fatality ratios (CFR) among hospitalized patients ranged from 36-66% depending on the age group, with CFR exceeding 60% for all age groups beyond 40 years; depending on the age group, Sp meningitis mortality incidences were 2 to 12-fold greater than those for meningococcal meningitis. The lifetime risks of pneumococcal meningitis disease and death were 0.6% (1 in 170) and 0.3% (1 in 304), respectively. The incidences of these outcomes were highest among children age <1 year. However, the cumulative risk was highest among persons age 5 to 59 years who experienced 59% of pneumococcal meningitis outcomes. After age 5 years and depending on the country, 59-79% of meningitis cases were caused by serotype 1.
In the African meningitis belt, Sp is as important a cause of meningitis as Neisseria meningitidis, particularly among older children and working age adults. The meningitis belt population needs an effective serotype 1 containing vaccine and policy discussions should consider vaccine use outside of early childhood.
PMCID: PMC2838886  PMID: 20146815
23.  Phenotypic Characterization and Antibiogram of CSF Isolates in Acute Bacterial Meningitis 
Context: Acute bacterial meningitis (ABM) is a medical emergency, which warrants an early diagnosis and an aggressive therapy. Despite the availability of potent newer antibiotics, the mortality rate caused by acute bacterial meningitis remains significantly high in India and in other developing countries, which ranges from 16 - 32%. There is a need of a periodic review of bacterial meningitis worldwide, since the pathogens which are responsible for the infection may vary with time, geography and the age of the patient.
Aims: Our aim was to study the bacterial profiles and antimicrobial susceptibility patterns of the CSF isolates which were obtained from patients of acute bacterial meningitis in our area.
Settings and Design: Two hundred and fifty two clinically diagnosed cases of acute bacterial meningitis, who were admitted to the wards of a tertiary medical centre in Patna, during the period from August 2011 to December 2012, were included in this study.
Material and Methods: Two hundred and fifty two CSF samples from as many patients of ABM were processed for cell counts, biochemical analysis, gram staining, culture, antigen detection by latex agglutination test (LAT) and antibiotic susceptibility tests, as per the standard techniques.
Results: In this study, 62.3% patients were males and 37.7% were females The most common age group of presentation was 12-60 years (80.2%). Gram stained smears were positive in 162 (64.3%) samples, while culture yielded positive growth in 200 (79.4%) patients. Streptococcus pneumoniae was the most common pathogen which was isolated in 120 (60%) culture positive cases. Cell counts showed the predominance of neutrophils in all cases with ABM. High protein and low sugar levels correlated well with the features of ABM. All gram positive isolates were sensitive to vancomycin. All the gram negative isolates were sensitive to imipenem. Twenty two (8.7%) patients expired during the course of study. Deaths were caused by N.meningitidis in 9 (40.9%) cases, by S.pneumoniae in 3 (13.6%) cases and by H.influenzea in 1 (4.5%) case. In the remaining 9 (40.9%) mortality cases, the organism could not be identified.
Conclusion: Simple, rapid, inexpensive tests like gram staining remain significant means for diagnosis of ABM in developing countries. LAT for pneumococcal antigen should be performed first, since Streptococcus pneumoniae remains the major aetiological agent of ABM, both in adults and children. The final diagnosis of ABM depends upon a comprehensive analysis of CSF smears, cultures, LAT, cytological, biochemical and clinical findings of the cases, and a single test or parameter cannot be used to decide the course of management in the patients. However, empirical therapy is advocated, considering the potentially high rate of mortality in these patients.
PMCID: PMC3919387  PMID: 24551618
Acute bacterial meningitis; Antimicrobial susceptibility pattern; Haemophilus influenzae; Neisseria meningitidis; Latex agglutination test; Pyogenic meningitis; Streptococcus pneumoniae
24.  Streptococcus pneumoniae meningitis in Alberta pre- and postintroduction of the 7-valent pneumococcal conjugate vaccine 
The objective of this study was to describe the epidemiology, clinical characteristics, microbiology and outcomes of patients of all ages with Streptococcus pneumoniae meningitis between 2000 and 2004; two years pre- and postintroduction of an S pneumoniae 7-valent conjugate vaccine program in Alberta in children younger than two years of age. The high mortality rate associated with S pneumoniae meningitis, despite appropriate therapy, suggests that prevention of S pneumoniae meningitis is critical. Despite implementation of a PCV-7 program in Alberta, rates of S pneumoniae meningitis in children younger than two years of age is still high. Thus, continued research into safe and efficacious vaccines covering a broader range of S pneumoniae serotypes is necessary.
To describe the epidemiology, clinical characteristics, microbiology and outcomes of patients of all ages with Streptococcus pneumoniae meningitis two years pre- and postintroduction of a S pneumoniae 7-valent conjugate vaccine program in Alberta in children <2 years of age.
Between 2000 and 2004, all cases of invasive pneumococcal disease in Alberta were identified. From this cohort, patients with S pneumoniae meningitis were identified by chart review. Clinical data, laboratory data and in-hospital outcomes were collected.
Of the 1768 cases of invasive pneumococcal disease identified between 2000 and 2004, 110 (6.2%) had S pneumoniae meningitis. The overall incidence was 0.7 per 100,000 persons and remained unchanged over the study period. The rate in children <2 years of age appeared to fall over time, from 10.5 per 100,000 persons in 2000 to five per 100,000 persons in 2004, although there was insufficient evidence of a statistically significant time trend within any age group. Overall, the mean age was 30 years and 47% were male. In-hospital mortality was 20%, ranging from 6% in those ≤2 years of age to 31% for those ≥18 years of age, despite appropriate antimicrobial therapy.
The high mortality rate associated with S pneumoniae meningitis suggests that prevention by vaccination is critical. In children <2 years of age, there was a downward trend in the rate of S pneumoniae meningitis after implementation of the S pneumoniae 7-valent conjugate vaccine program, but rates were still high.
PMCID: PMC3222760  PMID: 23205025
Conjugate; Meningitis; Streptococcus pneumoniae; Vaccine
25.  Emergence of Epidemic Neisseria meningitidis Serogroup X Meningitis in Togo and Burkina Faso 
PLoS ONE  2011;6(5):e19513.
Serogroup X meningococci (NmX) historically have caused sporadic and clustered meningitis cases in sub-Saharan Africa. To study recent NmX epidemiology, we analyzed data from population-based, sentinel and passive surveillance, and outbreak investigations of bacterial meningitis in Togo and Burkina Faso during 2006–2010. Cerebrospinal fluid specimens were analyzed by PCR. In Togo during 2006–2009, NmX accounted for 16% of the 702 confirmed bacterial meningitis cases. Kozah district experienced an NmX outbreak in March 2007 with an NmX seasonal cumulative incidence of 33/100,000. In Burkina Faso during 2007–2010, NmX accounted for 7% of the 778 confirmed bacterial meningitis cases, with an increase from 2009 to 2010 (4% to 35% of all confirmed cases, respectively). In 2010, NmX epidemics occurred in northern and central regions of Burkina Faso; the highest district cumulative incidence of NmX was estimated as 130/100,000 during March–April. Although limited to a few districts, we have documented NmX meningitis epidemics occurring with a seasonal incidence previously only reported in the meningitis belt for NmW135 and NmA, which argues for development of an NmX vaccine.
PMCID: PMC3098835  PMID: 21625480

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