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Bacterial Meningitis in Children < 2 Years of Age in a Tertiary Care Hospital in South India: An Assessment of Clinical and Laboratory Features
Abstract
To assess the clinical and laboratory features of suspected meningitis to assist in the accurate diagnosis of bacterial meningitis in young Indian children.
Children <2 years of age with clinical suspicion of meningitis were enrolled. Clinical and laboratory information was collected, and cases were classified based on cerebrospinal fluid findings as clinical, aseptic, or probable and confirmed bacterial meningitis.
A total of 2564 children with suspected meningitis were enrolled over 45 months; 156 cases of aseptic and 51 cases of bacterial meningitis were identified. Stiff neck and bulging fontanelle were more common in bacterial meningitis (P < .05), but were present in <15% of patients. The World Health Organization and American Academy of Pediatrics classifications for high suspicion of bacterial meningitis were met in 84% and 88% of cases of bacterial meningitis, respectively, but were also present in 54% and 74% cases of aseptic meningitis. Culture and gram stain were positive in 7 (14%) and 4 (8%) cases of bacterial meningitis.
Signs of bacterial meningitis and proposed criteria for high suspicion of bacterial meningitis are non-specific in this population. Standard microbiological tests for bacteria are insensitive in this setting, necessitating highly sensitive methods to identify bacterial meningitis.
... Respecto de la tinción Gram, es un método útil, rápido y económico que permite la identificación de patógenos en el LCR. En nuestro estudio, en el 79% de los casos no se ubicaron los resultados en las historias clínicas, pero en el 62% de los confirmados, los patógenos fueron Gram positivos, resultado similar a otras publicaciones que reportan una reducción en el 50% de la "positividad" en la tinción en pacientes que recibieron terapia antibiótica previa a la PL versus pacientes que no recibieron antibiótico 15,16 . ...
... En relación a los cultivos positivos de LCR, el patógeno más frecuentemente aislado fue S. pneumoniae (67%) y el menos frecuente N. meningitidis 8%, resultado similar a los reportados por otros estudios 8,14,16,19 . Se debe tener en consideración, que los patógenos suelen diferir según las edades y contextos de coberturas vacunales 15,18 . ...
... Por otro lado, observamos que en las historias clínicas del Instituto se registró como indicación médica estándar, que el tratamiento antibiótico se debía administrar posterior a la PL; lo cual no siempre se cumplió por diferentes razones (demora en la realización de la PL, o bien PL frustra, no autorización por los padres o responsables) y se pudo corroborar al revisar las horas de la primera infusión antibiótica en los kárdexs de enfermería con el día y hora de la PL. Otros estudios respaldan que el uso de antibiótico previo a la PL reduce la positividad en los cultivos en 9%, en comparación al 43% de positividad obtenido en aquellos que no recibieron terapia antibiótica previa, por lo que el uso de pruebas moleculares para mejorar la eficacia en el diagnóstico podría optimizar estos resultados 15,18 . ...
Introducción: El diagnóstico de meningitis bacteriana (MB) en pacientes pediátricos sigue siendo un reto, lo que subraya la necesidad de reevaluar los criterios clínicos, epidemiológicos y de laboratorio, para formular nuevas estrategias. Objetivos: Describir las características clínico-epidemiológicas de pacientes hospitalizados como casos confirmados, probables y sospechosos de MB en un Instituto del 2010- 2020. Métodos: El estudio fue retrospectivo, descriptivo en pacientes pediátricos hospitalizados. La población fue 363, la muestra 277 cuyo diagnóstico de ingreso incluía meningitis, se revisaron 269. Resultados: De 269, 188 fueron MB:13% confirmados, 15% probables y 72% sospechosos. La mediana de edad fue 2 años, 62.7% fueron de sexo masculino y 5% de letalidad. El 47.8% registró un esquema completo de inmunización contra Hib y 48.9% contra Neumococo. Las características clínicas frecuentes fueron: fiebre 88.8%, vómitos 49.5%, somnolencia 34.6% y convulsiones 36.2%. 79.3% recibieron tratamiento antibiótico previo a su ingreso al Instituto y 75.5% usó antibiótico previo a la punción lumbar (PL). Neumococo fue aislado en 67%, en 54% de los cultivos se obtuvo el antibiograma, todos sensibles a ceftriaxona y 15% resistente a vancomicina. Conclusiones: El uso de antibiótico empírico previo a la PL fue significativo para el bajo aislamiento de gérmenes en LCR en los casos sospechosos.
... Although the rate of disease associated with meningitis is lower than other major causes of childhood, mortality there are high case fatality rates and neurologic sequelae in survivors. 3 Aims and objectives 1. To evaluate the prescription pattern of antibiotics for pediatric patients suffering from meningitis. 2. To evaluate the efficacy of antibiotics, combination of antibiotics, and the resistance developed against them. ...
... Clinical presentation of meningitis in pediatric patients [1][2][3] are often less prominent than in adults. Fever was present in 70% of patients. ...
... Use of different types of cephalosporin in meningitis % Sensitivity/resistance pattern seen in gram +ve isolates et al.3 In our study, CSF culture and gram stain are positive in 5.8% and <5% cases. ...
Background: Meningitis, inflammation of the meninges with systemic septicemia, from the bacterial, viral, or fungal origin, is a fatal disease in all age groups, particularly infants and children. The present study was done to evaluate the usage of antibiotics in pediatric patients with meningitis in a tertiary care hospital. Aims and Objectives: The study was conducted to evaluate the prescription pattern of antibiotics for pediatric patients suffering from meningitis. The efficacy of antibiotics, combination of antibiotics, and the resistance developed against them were reevaluated. Materials and Methods: An observational, noninterventional study with 34 pediatric patients (The mean age of the patients were 6.17 year. ±4.84 SD) admitted in Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar from September 2012 to February 2014 were evaluated. Data were collected after the approval of the research protocol by the Institutional Ethics committee, KIMS from case sheets of patients from the ward as well as the Medical Record and Data section. Comparative statistical analysis was done by using student’s t-test in respect of data measured on a continuous scale. All differences with P<0.05 were labeled as statistically significant. Results: Ceftriaxone±ß lactamase inhibitor (βLI) (77.4%), and Cefoperazone±βLI (12.9%) were the most frequently used cephalosporin. In 55.8% of patients, three or more antibiotics in combination were given. Two drugs regimen like β lacatam+aminoglycoside in 23.5% of patients and β lactam+anti-Methicillin-resistant Staphylococcus aureus (MRSA) in 20.6% were given. Emerging resistance pattern against both Gram-positive cocci and Gram-negative bacilli to penicillins, cephalosporins, and aminoglycosides which are the primary first-line drugs has been observed. Conclusion: Very severe meningitis patients were treated with multiple antibiotics including anti-MRSA agents. High resistance (≥60%) was observed against β lactams.
... Although the rate of disease associated with meningitis is lower than other major causes of childhood, mortality there are high case fatality rates and neurologic sequelae in survivors. 3 Aims and objectives 1. To evaluate the prescription pattern of antibiotics for pediatric patients suffering from meningitis. 2. To evaluate the efficacy of antibiotics, combination of antibiotics, and the resistance developed against them. ...
... Clinical presentation of meningitis in pediatric patients [1][2][3] are often less prominent than in adults. Fever was present in 70% of patients. ...
... Use of different types of cephalosporin in meningitis % Sensitivity/resistance pattern seen in gram +ve isolates et al.3 In our study, CSF culture and gram stain are positive in 5.8% and <5% cases. ...
Background: Meningitis, inflammation of the meninges with systemic septicemia, from the bacterial, viral, or fungal origin, is a fatal disease in all age groups, particularly infants and children. The present study was done to evaluate the usage of antibiotics in pediatric patients with meningitis in a tertiary care hospital. Aims and Objectives: The study was conducted to evaluate the prescription pattern of antibiotics for pediatric patients suffering from meningitis. The efficacy of antibiotics, combination of antibiotics, and the resistance developed against them were reevaluated. Materials and Methods: An observational, noninterventional study with 34 pediatric patients (The mean age of the patients were 6.17 year. ±4.84 SD) admitted in Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar from September 2012 to February 2014 were evaluated. Data were collected after the approval of the research protocol by the Institutional Ethics committee, KIMS from case sheets of patients from the ward as well as the Medical Record and Data section. Comparative statistical analysis was done by using student’s t-test in respect of data measured on a continuous scale. All differences with P<0.05 were labeled as statistically significant. Results: Ceftriaxone±ß lactamase inhibitor (βLI) (77.4%), and Cefoperazone±βLI (12.9%) were the most frequently used cephalosporin. In 55.8% of patients, three or more antibiotics in combination were given. Two drugs regimen like β lacatam+aminoglycoside in 23.5% of patients and β lactam+anti-Methicillin-resistant Staphylococcus aureus (MRSA) in 20.6% were given. Emerging resistance pattern against both Gram-positive cocci and Gram-negative bacilli to penicillins, cephalosporins, and aminoglycosides which are the primary first-line drugs has been observed. Conclusion: Very severe meningitis patients were treated with multiple antibiotics including anti-MRSA agents. High resistance (≥60%) was observed against β lactams.
... Of the 13 studies in the endemic conditions, 11 studies (in hospital/laboratory settings) reported the number of confirmed cases of Meningococcal meningitis among clinically suspected patients in different regions of India. [21][22][23][24][25][26][27][28][29][30]50,55 The overall estimate of the prevalence (proportion) of the confirmed Meningococcal meningitis cases among 21 049 clinically suspected patients was 0.76% (95% CI: 0.3-1.4) (Figure 3). ...
... Of the 13 studies, 10 reported age distribution for sporadic cases of Meningococcal meningitis. Seven studies involved pediatric patients 21,22,25,27,29,31,50 one involved adults, 23 and 1 study reported the presence of N. meningitidis in neonates (n = 1) 24 and mixed population (involving adolescents and adults). 28 In the remaining 3 studies, age distribution was unclear for confirmed cases of Meningococcal meningitis but defined for total cases (which included suspected cases of the disease) and indicated a trend among adolescents and adults. ...
... Only 4 studies reported information of serogroup, of which 2 studies reported non-specific serogroup ACWY. 21,25 ...
Objective
To perform systematic review and meta-analysis of meningococcal disease burden in India.
Methods
We searched publications on meningococcal disease in India between 1996 and 2020 using PubMed and Google Scholar. Prevalence (proportion) of Meningococcal meningitis and Case-fatality ratio (CFR) were pooled using random effects model. Other outcomes were pooled qualitatively.
Results
The prevalence of Meningococcal meningitis in epidemic and endemic conditions was 12.1% (95% CI: 5.2-21.4) and 0.76% (95% CI: 0.3-1.4), respectively, with a CFR of 12.8% (95% CI: 6.8-20.4) in epidemic settings; N. meningitis caused 3.2% (95% CI: 1.6-5.3) of Acute Bacterial Meningitis (ABM) cases in endemic settings. The disease appeared in infants, adolescents, and adults with Serogroup A prevalence. Treatment and prophylaxis were limited to antibiotics despite increased resistance.
Conclusion
The study reveals epidemic and endemic presence of the disease in India with high fatality and serogroup A prevalence. Further monitoring and immunization are required to prevent outbreaks.
... Finally, 32 publications reporting data from original studies were included in this review [16, (Fig. 2). These 32 publications reported data on meningococcal disease from different regions of India: Delhi (n = 11) [16, 24-26, 34, 40, 45-47, 52, 53], Karnataka (n = 5) [36,43,44,49,50], Assam (n = 3) [28,32,33], Kashmir (n = 2) [27,41], Chandigarh (n = 2) [37,51], Meghalaya (n = 2) [30,31], multiple states (n = 2) [38,39], Maharashtra (n = 1) [29], Uttar Pradesh (n = 1) [23], Odisha (n = 1) [48], Tripura (n = 1) [42] and Tamil Nadu (n = 1) [35] ( Table 2). ...
... An equal number of publications reported data for the pediatric population (n = 11) [23,25,29,35,38,46,[48][49][50][51][52] and mixed populations of different age groups including neonatal, pediatric, adolescent and adult, respectively [16,28,30,34,36,39,40,42,43,45,47]. A few publications reported data specifically for adult (n = 5) [26,27,41,44,53], adolescent (n = 3) [24,31,37] and neonatal (n = 2) [32,33] populations, respectively ( Table 2). ...
... Most publications reported percentages of confirmed cases in the range of 0.1 (n = 2)-7.6% (n = 18) [28,29,32,35,36,38,43,[49][50][51] of suspected cases, and in one publication from Delhi, 71.4-100% (n = 34) of the samples were positive for N.meningitidis, depending on the technique used for diagnosis [40]. Mortality was not reported in any of these publications ( Table 2). ...
Introduction:
Meningococcal disease caused by Neisseria meningitidis has a high case fatality rate. Of 12 distinct serogroups, A, B, C, W-135 (W) and Y cause the majority of infections. The meningococcal disease burden and epidemiology in India are not reliably known. Hence, we performed a narrative review with a systematically conducted search to summarize information on meningococcal disease burden and epidemiology and vaccination recommendations for meningococcal disease in India.
Methods:
A search of Medline and Embase databases was undertaken to identify relevant publications published in the last 25 years.
Results:
Results from 32 original publications, 11 of which were case reports, suggest a significant burden of meningococcal disease and related complications. Meningococcal disease is increasingly reported among adolescents and adults, and large outbreaks have been reported in this population. Meningococcal disease in India is caused almost exclusively by serogroup A; serogroups B, C, W and Y have also been documented. Meningococcal disease burden data remain unreliable because of limited disease surveillance, insufficient laboratory capacity, misdiagnosis and prevalence of extensive antibiotic use in India. Lack of access to healthcare also increases under-reporting, thus bringing the reliability of the data into question. Conjugate meningococcal vaccines are being used for disease prevention by national governments and immunization programs globally. In India, meningococcal vaccination is recommended only for certain high-risk groups, during outbreaks and for international travelers such as Hajj pilgrims and students pursuing studies abroad.
Conclusion:
Meningococcal disease is prevalent in India but remains grossly underestimated and under-reported. Available literature largely presents outbreak data related to serogroup A disease; however, non-A serogroup disease cases have been reported. Reliable epidemiologic data are urgently needed to inform the true burden of endemic disease. Further research into the significance of meningococcal disease burden can be used to improve public health policy in India. Fig. 1 Plain language summary.
... Surveillance for bacterial meningitis was previously established in four hospitals in India (Christian Medical College in Vellore, Tamilnadu; the Institute of Child Health and Hospital for Children in Chennai, Tamilnadu; Chhatrapati Shahuji Maharaj Medical University in Lucknow, Uttar Pradesh and Kalawati Saran Children's Hospital in New Delhi) beginning July 2008 in an effort to define the burden of meningitis due to Hib and other bacterial pathogens, and assess the need for prevention and treatment strategies. Details of this surveillance effort have been published previously [9,10]. In December 2011 Hib-CV was introduced in Tamilnadu as a part of a pentavalent combination vaccine which included the following antigens: Diphtheria-Tetanus-Pertussis (DTP), Hepatitis B, and Hib-CV. ...
... If the CSF volume obtained was limited, the available CSF was prioritized for sequential testing with WBC, LAT, and biochemistry. CSF bacterial culture was not prioritized as prior experience showed limited sensitivity for detecting bacterial meningitis in this population [9,10]. LAT could also be performed at the attending physicians request, regardless of other CSF findings, if the clinical suspicion for bacterial meningitis was high. ...
... Between January 2009 and March 2014, 4,770 children with clinically suspected meningitis were enrolled (Table 1). A combination of fever, seizures, and altered consciousness were the most common indicators for suspicion of meningitis; a more thorough description of the clinical characteristics of suspected meningitis in this population has been described previously [9]. LAT was performed on 608 CSF samples; 337 tests were performed on CSF with 10 WBCs per mm 3 and 271 were done CSF on samples with <10 WBCs per mm 3 . ...
Introduction
Haemophilus influenzae type b was the leading cause of bacterial meningitis in infants and children below the age of two years prior to the introduction of H. influenzae type b conjugate vaccines. In December 2011, the Indian government introduced H. influenzae b vaccine in the state of Tamilnadu. A prospective surveillance for bacterial meningitis was established at the Institute of Child Health in Chennai to evaluate the etiology of meningitis and impact of the vaccine.
Material and Methods
Infants aged one to 23 months who were admitted to the hospital with symptoms of suspected bacterial meningitis were enrolled and lumbar puncture was performed. Cerebrospinal fluid samples were analyzed for white blood cells, protein, and glucose. Bacterial culture and a latex agglutination test for common bacterial pathogens were performed.
Results
Between January 2009 and March 2014, 4,770 children with suspected bacterial meningitis were enrolled. Prior to the introduction of the vaccine, an average of 11.7 cases of H. influenzae b meningitis and 31.1 cases of probable meningitis with no etiology were identified each year. After introduction, the number of cases were reduced by 79% and 44% respectively. The average H. influenzae b vaccine coverage after introduction was 69% among all children with clinically suspected meningitis. In contrast, the mean number of aseptic meningitis and pneumococcal meningitis cases remained stable throughout the pre and post vaccination period; 28.2 and 4.8 per year, respectively.
Conclusions
H. influenzae b conjugate vaccine reduced the number of cases of H. influenzae b meningitis and probable meningitis within the first two years of its introduction. The impact against meningitis was higher than the vaccination rate, indicating indirect effects of the vaccine. India has recently scaled up the use of Hib conjugate vaccine throughout the country which should substantially reduce childhood meningitis rates further in the country.
... While not a formal measure in our study, clinical experience informs us that many patients may go days on antibiotic therapy in this context whereas in the U.S. the comparisons were between 12-24 hours of antibiotic pretreatment. Another study done in India also did not find a difference in CSF WBC count between pretreatment and no pretreatment, with the primary difference between that study and this one being their focus on children <2 years of age (14). ...
... The implications of using broad clinical criteria for acute meningitis syndrome include overtreatment of children who have viral or aseptic meningitis and potentially inducing antibiotic resistance. Other studies have highlighted the poor performance of clinical predictors of bacterial meningitis (6,9,14), or they have found positive clinical predictors of only severe presentations or findings, e.g. loss of consciousness (15). ...
... High levels of prior antibiotic use have been found in other developing world analyses of acute meningitis syndrome (14). Addressing inappropriate antibiotic use in the developing world has several challenges. ...
Background
Bacterial meningitis is a significant cause of morbidity and mortality in the developing world. However, limited research has focused on the diagnosis and management of meningitis in resource-limited settings.
Methods
We designed a prospective case series of children admitted to a large, academic referral hospital with acute meningitis syndrome. Data were collected on age, time of presentation, prior antibiotics, cerebrospinal fluid (CSF) parameters, antibiotic and steroid prescription, and clinical outcome.
Results
Data on 99 patients were collected and analyzed. Most of the patients were males, n=69 (70%), and were from a rural area, n=83 (84%). Incomplete vaccination was common, n=36 (36%) and many have evidence of malnutrition, n=25 (38%). Most patients, n=64 (72%), had received antibiotics prior to admission with a mean duration of symptoms of 4.9 days prior to admission. The CSF white blood cell (WBC) count was higher in those who had not received prior antibiotics though it was elevated in both groups. The CSF WBC count was not associated with survival; malnutrition and length of symptoms prior to admission were both associated with decreased survival.
Conclusions
While use of antibiotics prior to obtaining CSF in patients with acute meningitis syndrome may decrease their CSF WBC count, it is not clinically significant. Many patients had a significant delay in presentation that had an effect on survival, This is a potentially modifiable risk factor despite the resourcelimited setting.
... While not a formal measure in our study, clinical experience informs us that many patients may go days on antibiotic therapy in this context whereas in the U.S. the comparisons were between 12-24 hours of antibiotic pretreatment. Another study done in India also did not find a difference in CSF WBC count between pretreatment and no pretreatment, with the primary difference between that study and this one being their focus on children <2 years of age (14). ...
... The implications of using broad clinical criteria for acute meningitis syndrome include overtreatment of children who have viral or aseptic meningitis and potentially inducing antibiotic resistance. Other studies have highlighted the poor performance of clinical predictors of bacterial meningitis (6,9,14), or they have found positive clinical predictors of only severe presentations or findings, e.g. loss of consciousness (15). ...
... High levels of prior antibiotic use have been found in other developing world analyses of acute meningitis syndrome (14). Addressing inappropriate antibiotic use in the developing world has several challenges. ...
BACKGROUND: Bacterial meningitis is a significant cause of morbidity and mortality in the developing world. However, limited research has focused on the diagnosis and management of meningitis in resource-limited settings. METHODS: We designed a prospective case series of children admitted to a large, academic referral hospital with acute meningitis syndrome. Data were collected on age, time of presentation, prior antibiotics, cerebrospinal fluid (CSF) parameters, antibiotic and steroid prescription, and clinical outcome. RESULTS: Data on 99 patients were collected and analyzed. Most of the patients were males, n=69 (70%), and were from a rural area, n=83 (84%). Incomplete vaccination was common, n=36 (36%) and many have evidence of malnutrition, n=25 (38%). Most patients, n=64 (72%), had received antibiotics prior to admission with a mean duration of symptoms of 4.9 days prior to admission. The CSF white blood cell (WBC) count was higher in those who had not received prior antibiotics though it was elevated in both groups. The CSF WBC count was not associated with survival; malnutrition and length of symptoms prior to admission were both associated with decreased survival. CONCLUSIONS: While use of antibiotics prior to obtaining CSF in patients with acute meningitis syndrome may decrease their CSF WBC count, it is not clinically significant. Many patients had a significant delay in presentation that had an effect on survival, This is a potentially modifiable risk factor despite the resource-limited setting.
... Acute meningitis in children causes significant morbidity. 1 Infectious agents of meningitis include bacteria, viruses, fungus, and other microorganisms. Viral meningitis is more common and bacterial meningitis is more severe. ...
... About 71% of cases of bacterial meningitis had >100 WBC/mm 3 , 40% had glucose levels <40 mg/dL, and 58% had protein level >100 mg/dL, compared with 33, 21, and 23% of respective variables in patients with ASM. 1 In the present study, the median CSF WBC observed in bacterial meningitis, APBM, and ASM groups were 310, 125, and 140 cells/mm 3 , respectively. ...
... Akpede et al. found it strongly associated with bacterial meningitis, along with focal seizures [5]. However, other studies demonstrated that the strongest clinical predictors for bacterial meningitis in an infant are toxic appearance and convulsions [6] and that a bulging fontanelle is present in less than 15% of cases [7]. ...
... Previous studies also confirm that the strongest clinical predictors for bacterial meningitis in an infant are appearing ill and convulsions. A bulging fontanelle is present in less than 15% of the cases [7]. ...
It is common practice to perform a lumbar puncture in infants presenting with fever and a bulging fontanelle in order to rule out bacterial meningitis. However, most of these infants have benign, self-limiting diseases. The objective was to determine whether there is an association between bulging fontanelle and bacterial meningitis in febrile infants. This retrospective cohort study included febrile children with a bulging fontanelle who underwent lumbar puncture at Meir Medical Center from 2005 through 2015. A total of 764 children ages 2–18 months underwent lumbar puncture during the study period. Among them, 304 had a bulging fontanelle and fever on evaluation and cerebrospinal fluid pleocytosis was found in 115 (37.8%), including 1 case of bacterial meningitis (0.3%). None of the infants described on admission as appearing well on presentation was found to have bacterial meningitis. Of the 764 children who underwent lumbar puncture, 10 infants were diagnosed with bacterial meningitis, and only one (10%) presented with a bulging fontanelle.
Conclusion: The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis. Most causes of a bulging fontanelle in febrile infants are self-limiting diseases. The routine approach of performing a lumbar puncture in febrile infants with a bulging fontanelle should be reconsidered.What is Known:
• It is common to perform a lumbar puncture in febrile infants with a bulging fontanelle, to rule out bacterial meningitis.
• However, there are only few researches regarding the relationship between bulging fontanelle and bacterial meningitis.
What is New:
• The finding of a bulging fontanelle has very low sensitivity and specificity for bacterial meningitis
• The need for routine lumbar puncture in these cases should be reconsidered.
... 8 The prevalence of neck stiffness and bulging anterior fontanelle was reported to be < 15% in bacterial meningitis patients aged < 2 years. 9 In our study, there was no significant difference between the groups in terms of the prevalence of meningeal irritation signs. Moreover, while the specificity of meningeal irritation signs in diagnosing meningitis was 74.5%, the sensitivity was found to be quite low (26%). ...
... The positivity of CSF Gram stain and culture in children aged < 2 years with bacterial meningitis was reported to be 14 and 8%, respectively. 9 In another study in children with meningitis sensitivity of CSF Gram staining and CSF culture were found as 69.1 and 81.6%, respectively. 12 In our study, positivity rate of the CSF Gram staining and culture in bacterial meningitis was low, at 25 and 31.2%, ...
Objective Acute meningitis in childhood is a serious infectious disease that requires immediate medical assessment to ensure appropriate treatment and healthy outcomes. The aim of this retrospective study was to evaluate clinical and laboratory findings in the diagnosis of acute meningitis in children.
Methods Between February 2011 and March 2013, 258 children aged between 1 month and 18 years who were admitted to Konya Training and Research Hospital, Turkey, with clinically suspected meningitis and undergoing lumbar puncture were enrolled in the study. Patient charts were reviewed using a standardized data collection tool. Fifty-nine patients were excluded because of incomplete data or because they did not meet the enrollment criteria. Further statistical analysis was conducted on the remaining 199 patients. The diagnostic values of clinical and laboratory findings for acute meningitis were investigated. IBM SPSS 21.0 for Windows was used for the statistical analysis.
Results Of the 199 patients (61.3% male; median age: 24 months), 101 (50.8%) were diagnosed with meningitis. A definitive diagnosis of bacterial meningitis was made in 16 patients, while 5 patients had probable bacterial meningitis. In addition, 80 patients diagnosed as aseptic meningitis and 47 of these patients had human enterovirus meningitis. Headache was more common in patients with meningitis. In patients without meningitis, the most common complaints were seizures or seizures accompanied by fever. Erythrocyte sedimentation rates (ESR), levels of cerebrospinal fluid protein, and cell counts in cerebrospinal fluid examinations were higher in the meningitis group. C-reactive protein, ESR, and procalcitonin higher than 22.55 mg/L, 36.5 mm/hour, and 6.795 mg/mL, respectively, indicated bacterial meningitis.
Conclusion Our results showed that a combination of clinical and laboratory markers could facilitate recognition of bacterial meningitis in children
... A prevalência depende da etiologia, sendo as virais mais frequentes que as bacterianas, e estas, por sua vez, mais comuns que as demais etiologias (3) . As meningites virais são diagnósticos de exclusão com base na falta de achados bacterianos no Líquido Cefalorraquidiano (LCR), geralmente apresentando gravidade menor em relação às bacterianas e podendo, ainda, aparecer na forma de um surto (4,5) . ...
... Esta semelhança nas taxas entre os estudos deve-se ao fato de que o quadro clínico de meningite em recém-nascidos é inespecífico, podendo ser semelhante ao de outras doenças febris (3) . (11)(12)(13) . ...
This article aims to analyze the prevalence of meningitis in patients who underwent diagnostic evaluation by lumbar puncture in the emergence of a children's hospital. The methodology was a cross-sectional observational study, retrospective, descriptive and quantitative approach. 261 children were investigated between 0 and 14 years, with suspected meningitis, admitted at the emergency of a children's hospital reference in the south of Santa Catarina, between the years 2012 and 2013. The results showed that the prevalence of meningitis founded was 25,3% (n=66). Those aged less than one month, 100% of cases (n=12) had viral or aseptic etiologies. In patients older than one month, 88,9% (n=48) were viral or aseptic; 1,85% (n=1), possibly bacterial; 5,55% (n=3) had bacterial meningitis; 1,9% (n=1) had fungal and 1,9% (n=1) carried tuberculous meningitis. Clinical manifestations in patients aged more than one month, met meningeal sign in 25,9% (n=14) and vomiting in 57,4% (n=31), and both had p <0.05. We saw that the predominance of lymphocytes in cerebrospinal fluid was positively correlated with viral meningitis (96,7%), fungal (100%) and tuberculosis (100%). It was concluded that the prevalence of meningitis in children aged less than or equal to one month was 20,7%, all of which were of viral or aseptic etiologies. In infants greater than one month year old, the prevalence was 26,6% or viral etiologies such as aseptic main (88,9%), followed by bacterial (7,4%), fungal (1,9%) and tuberculosis (1,9%). The prevalence of meningitis in the total sample was 25,3%.
... These complications pose a significant threat to the life and health of children, especially infants and young children who have an immature blood-brain barrier. In addition, due to the immature immune system of newborns, the incidence is significantly higher than any other period, and its mortality is still high [16].In fact, the incidence of suppurative meningitis is significantly higher in infants and young children compared to older children, making it a leading cause of death and disability [4,17,18]. The rates of morbidity and mortality vary across different countries and regions, with developed countries showing significantly lower rates compared to developing countries [19]. ...
Background
Meningitis can be caused by a variety of pathogenic microorganisms, which can lead to higher mortality and disability rates. However, the clinical manifestations of suppurative meningitis are often atypical in infants and young children, which makes early clinical diagnosis difficult.PAR and LAR are considered as a novel inflammatory biomarker and have been applied in tumors, IgA nephropathy, sepsis.
Objective
To investigate the application of platelet/albumin (PAR) and lactate dehydrogenase/albumin (LAR) in refractory suppurative meningitis in infants.
Methods
The relevant clinical data of 107 children with suppurative meningitis were retrospectively analyzed, and were divided into common group (82 cases) and refractory group (25 cases) according to the severity of the disease according to the relevant clinical consensus. The relevant clinical data and laboratory examination of the children in the two groups were compared. The diagnostic value of PAR and LAR in children with refractory suppurative meningitis was analyzed and multivariate Logistic regression analysis was performed.
Result
The PAR of children with suppurative meningitis in refractory group was lower than that in common group (P < 0.05), while LAR was higher than that in common group (P < 0.05). Meanwhile, multivariate Logistic regression analysis showed that LAR and cerebrospinal fluid glucose ≤ 1.5mmo/L were risk factors for poor prognosis (OR > 1, P < 0.05). PAR was a protective factor (OR < 1, P < 0.05).
Conclusion
PAR and LAR can be used for early diagnosis of refractory suppurative meningitis in children as protective and risk factors, respectively.
... Results of present study were not in line with other pediatric age group studies. 18,19 Vaccine strategies are being encouraged across the country, inclusion of Hemophilus influenzae type b (Hib) vaccine in the national immunization schedule had increased the coverage for the same, the availability and prescription for Pneumococcal vaccine has also increased in the recent times, evolving trends in the causative agents for bacterial meningitis are hence warranted. Present study was limited as latex agglutination test was not done for the detection for causative agents in pyogenic meningitis and PCR for complete virologic screening was not available for detection of causative agents for viral meningoencephalitis. ...
... In the viral meningitis group, the presenting symptoms were fever, headache, vomiting, and seizures. There was a distinct lack of difference in symptoms between cases of bacterial and aseptic meningitis as seen in previous studies (14). Out of 105 cases of viral meningitis, etiology could be established in only 33% cases, 19% tested positive for HSV and 14% were positive for Enterovirus establishing more prevalence of HSV in our study population which is in contrast with the other studies in South Asian region (15). ...
Background and objectives: Conventional culture and
sensitivity methods take around 48 hours to generate antibiotic sensitivity results after a blood culture is flagged as positive by automated systems. However, it is imperative to initiate early targeted antibiotic therapy for effective management of sepsis and to reduce morbidity, mortality, and cost of treatment. This study aimed to evaluate the direct sensitivity test (DST) as a potential tool to obtain quicker antibiotic susceptibility results from positive BacT/ALERT blood culture vials and the VITEK-2 system (the reference method).
Methods: Blood culture bottles flagged as positive by BacT/ALERT were Gram-stained. Cultures with polymicrobial growth were excluded from the study. The isolates were then simultaneously cultured and processed for the DST using the disk diffusion method. Agreements or errors were interpreted according to the Clinical and Laboratory Standards Institute’s guidelines.
Results: Among 76 Gram-positive isolates, we observed 99.2% essential agreement between the DST and AST. The rate of minor and major errors was 4.04% and 1.18%, respectively. Among 75 Gram-negative isolates, we observed 98.99% essential agreement between the DST and AST. The rate of minor and major errors was 4% and 2%, respectively. No very major error was seen in either Gram-negative or -positive isolates.
Conclusions: The DST results are available earlier than the AST results, which can ultimately help in the early initiation of targeted antibiotic therapy.
... white cells/mm3 for neonate and >5 white cells/mm3 for others and findings of biochemical and cytological analysis were in consistent with other studies [6,18,20]. It was observed 100% raised serum CRP in bacterial meningitis which is in accordance with P L have been reported to be useful to distinguish bacterial meningitis from aseptic meningitis [22], they were not routinely checked in our department due to high cost. ...
... In this study, 64.2% cases with ABM were boys. Bari et al in a local study 10 found 69.8% of the cases with meningitis to be boys while in another study from Rawalpindi 11 , male predominance as 58% was reported which is again close to what we noted in the present study. A study from Yemen also recorded 69% of the study participants to be male which shows that the regional data in terms of gender distribution also favoring our findings. ...
Objective: To determine the frequency of haemophilus influenzae infection in children less than 5 years with acute bacterial meningitis (ABM). Study Design: Descriptive Cross Sectional study. Setting: Department of Pediatric Medicine, The Children’s Hospital and Institute of Child Health, Multan. Period: October 2019 to March 2020. Material & Methods: A total of 165 children aged 5 – 60 months of either gender having acute bacterial meningitis with duration of < 2 weeks were enrolled. Cerebrospinal fluid (CSF) of each child was sent for microbiological analysis. Results: There were 106 (64.2 %) boys and 59 (35.8 %) girls. Mean age was 2.72 ± 1.07 years. Most cases, 112 (67.9 %) belonged to urban areas. Maternal literacy was positive in 65 (39.4%) cases while 59 (35.8%) were fully vaccinated. Mean disease duration was 56.25 ± 15.36 hours and 112 (67.9%) had duration of illness more than 36 hours. Frequency of Haemophilus Influenzae was noted in 35 (21.2%) cases. Conclusion: Frequency of Haemophilus Influenzae was high among children with acute bacterial meningitis. Early diagnosis and appropriate management might help reducing prolonged hospitalization and disease morbidity related to Haemophilus Influenza.
... Results of present study were not in line with other pediatric age group studies. 18,19 Vaccine strategies are being encouraged across the country, inclusion of Hemophilus influenzae type b (Hib) vaccine in the national immunization schedule had increased the coverage for the same, the availability and prescription for Pneumococcal vaccine has also increased in the recent times, evolving trends in the causative agents for bacterial meningitis are hence warranted. Present study was limited as latex agglutination test was not done for the detection for causative agents in pyogenic meningitis and PCR for complete virologic screening was not available for detection of causative agents for viral meningoencephalitis. ...
Background: CNS infections have been linked to adverse neurological sequelae notably seizures and mortality. Although, various etiologies of AFE have been studied, but the mystery still remains untangled for the substantial risk factors for the diagnosis and outcome.Methods: This prospective study was carried out on 67 children between 2 months to 15 years, from (May 2016 to April 2017) tertiary care centre of Uttarakhand. Patients were analysed for demographic variables, haematological parameters, CSF analysis, neuroimaging and their outcome was assessed at one month of follow up.Results: This study showed, 70% (n=47) of the cases presented in acute febrile encephalopathy. Most cases were diagnosed with pyogenic meningitis (40%, n=27) and More commonly occur during rainy season (39%; n=26) radiologically meningeal enhancement (28%; n=18) as the most common finding. Cases of acute febrile encephalopathy with GCS ≤5 had significant association with mortality. (Fischer exact value of 0.005; significant at p<0.05).Conclusions: Clinical signs of meningitis are not always reliable, and a laboratory support is required to reach early diagnosis hence. Pseudomonas and MRCONS were the major pathogens responsible for the bacterial meningitis among the paediatric age groups, hence antibiotic management should be planned intensively while culture reports are awaited. Cluster of cases with meningoencephalitis were found in rainy season hence suggested possible etiologies are JE/ Scrub/ Enterovirus. Mortality as well as morbidity was high in cases with acute encephalitis syndrome cause? JE/unknown etiology in this era for modern medicine hence vector control strategies be encouraged.
The cytologic evaluation of exfoliative and fine needle aspiration material is one of the most widely used diagnostic modalities worldwide. Now thoroughly updated with new guidelines and references, and featuring more than 1000 high-quality color photomicrographs, Differential Diagnosis in Cytopathology remains the essential organ-based reference guide for practising and trainee pathologists and cytotechnologists. This new edition addresses a comprehensive variety of benign and malignant neoplastic conditions, utilizing a consistent structure with bullet-point text for quick access and assimilation. The full spectrum of infectious and inflammatory disorders are also presented in detail. The information is not limited to light microscopic findings but includes many other genetic, molecular, and immunologic diagnostic modalities, giving readers the diagnostic and clinical criteria needed when formulating a diagnosis and differential diagnosis. No other book focuses exclusively on essential diagnostic criteria, making this an essential text for pathologists, cytopathologists and cytotechnologists at all stages of their careers.
The cytologic evaluation of exfoliative and fine needle aspiration material is one of the most widely used diagnostic modalities worldwide. Now thoroughly updated with new guidelines and references, and featuring more than 1000 high-quality color photomicrographs, Differential Diagnosis in Cytopathology remains the essential organ-based reference guide for practising and trainee pathologists and cytotechnologists. This new edition addresses a comprehensive variety of benign and malignant neoplastic conditions, utilizing a consistent structure with bullet-point text for quick access and assimilation. The full spectrum of infectious and inflammatory disorders are also presented in detail. The information is not limited to light microscopic findings but includes many other genetic, molecular, and immunologic diagnostic modalities, giving readers the diagnostic and clinical criteria needed when formulating a diagnosis and differential diagnosis. No other book focuses exclusively on essential diagnostic criteria, making this an essential text for pathologists, cytopathologists and cytotechnologists at all stages of their careers.
The cytologic evaluation of exfoliative and fine needle aspiration material is one of the most widely used diagnostic modalities worldwide. Now thoroughly updated with new guidelines and references, and featuring more than 1000 high-quality color photomicrographs, Differential Diagnosis in Cytopathology remains the essential organ-based reference guide for practising and trainee pathologists and cytotechnologists. This new edition addresses a comprehensive variety of benign and malignant neoplastic conditions, utilizing a consistent structure with bullet-point text for quick access and assimilation. The full spectrum of infectious and inflammatory disorders are also presented in detail. The information is not limited to light microscopic findings but includes many other genetic, molecular, and immunologic diagnostic modalities, giving readers the diagnostic and clinical criteria needed when formulating a diagnosis and differential diagnosis. No other book focuses exclusively on essential diagnostic criteria, making this an essential text for pathologists, cytopathologists and cytotechnologists at all stages of their careers.
This study evaluated the diagnostic role of cerebrospinal fluid leucine-rich alpha-2 glycoprotein (CSF LRG) concentration in children with acute bacterial meningitis, and its role in differentiation from aseptic meningitis. CSF LRG concentration was measured by ELISA Kit of 50 children with bacterial meningitis, 16 aseptic meningitis, and 20 children with normal CSF; control. CSF LRG was significantly elevated (p < 0.001) in bacterial meningitis with a sensitivity, specificity, PPV, and NPV of 96%, 100%, 100%, and 90.9%, respectively at a cutoff of 110.0 ng/mL, based on ROC curve. At the same cutoff value, CSF LRG has sensitivity, specificity, PPV, and NPV of 96%, 75%, 92.3%, and 85.7%, respectively in differentiating bacterial from aseptic meningitis. However, sensitivity, specificity, PPV, and NPV at 139.9 ng/mL for differentiating between definite and probable bacterial meningitis were 88%, 75%, 79.1%, and 84.9%, respectively. CSF LRG should be used as a diagnostic biomarker for bacterial meningitis.
Objectives:
The study aimed to understand the organism spectrum and antibiotic sensitivity profile of acute bacterial meningitis in pediatric population.
Methods:
A cross-sectional study was conducted at the department of microbiology of a tertiary care center for a period of 18 months. Suspected cases of meningitis between 1 and 60 months of age were considered for the study. All cases underwent cerebrospinal fluid tap for direct microscopy (DM), Gram staining, and culture sensitivity.
Results:
The mean age of the study patients was 10.42 months, with 61.7% of males and 38.3% of females. DM and culture were positive in 22.90% and 28.00% of the patients, respectively. On Gram stain, there were 29 (59.18%) cases of Gram positivity and 20 (40.82%) cases of Gram negativity. The culture growth showed that Acinetobacter spp. was isolated in 15 (30.6%) of the cases. Enterococcus spp. was isolated in 9 (18.4%) of the cases. Klebsiella pneumoniae was isolated in 8 (16.3%) of the cases. Staphylococcus aureus was isolated in 8 (16.3%) of the cases. Enterobacter spp. was isolated in 3 (6.12%) of the cases. Pseudomonas aeruginosa was isolated in 3 (6.12%) of the cases. Streptococcus pneumoniae was isolated in 3 (6.1%) of the cases. The antibiogram of different agents showed wide variation, with colistin being 100% sensitive for Acinetobacter, Enterobacter, K. pneumoniae, and P. aeruginosa.
Conclusion:
The present study revealed that Acinetobacter, Enterococcus, K. pneumoniae, and S. aureus were the most common bacterial etiologic agents of ABM. The 100% antibiotic sensitivity of the organisms to some antibiotics may suggest the use of such antibiotics while awaiting for culture sensitivity reports.
Background:
Bacterial meningitis is a significant cause of morbidity and mortality worldwide among children aged 1-59 months. We aimed to describe its burden in South Asia, focusing on vaccine-preventable aetiologies.
Methods:
We searched five databases for studies published from January 1, 1990, to April 25, 2017. We estimated incidence and aetiology-specific proportions using random-effects meta-analysis. In secondary analyses, we described vaccine impact and pneumococcal meningitis serotypes.
Results:
We included 48 articles cumulatively reporting 20,707 cases from 1987 to 2013. Mean annual incidence was 105 (95% confidence interval [CI], 53-173) cases per 100,000 children. On average, Haemophilus influenzae type b (Hib) accounted for 13% (95% CI, 8-19%) of cases, pneumococcus for 10% (95% CI, 6-15%), and meningococcus for 1% (95% CI, 0-2%). These meta-analyses had substantial between-study heterogeneity (I2 > 78%, P < 0.0001). Among studies reporting only confirmed cases, these three bacteria caused a median of 78% cases (IQR, 50-87%). Hib meningitis incidence declined by 72-83% at sentinel hospitals in Pakistan and Bangladesh, respectively, within two years of implementing nationwide vaccination. On average, PCV10 covered 49% (95% CI, 39-58%), PCV13 covered 51% (95% CI, 40-61%), and PPSV23 covered 74% (95% CI, 67-80%) of pneumococcal meningitis serotypes. Lower PCV10 and PCV13 serotype coverage in Bangladesh was associated with higher prevalence of serotype 2, compared to India and Pakistan.
Conclusions:
South Asia has relatively high incidence of bacterial meningitis among children aged 1-59 months, with vaccine-preventable bacteria causing a substantial proportion. These estimates are likely underestimates due to multiple epidemiological and microbiological factors. Further research on vaccine impact and distribution of pneumococcal serotypes will inform vaccine policymaking and implementation.
OBJECTIVE
Central nervous system (CNS) infections cause significant morbidity and mortality and often require neurosurgical intervention for proper diagnosis and treatment. However, neither the international burden of CNS infection, nor the current capacity of the neurosurgical workforce to treat these diseases is well characterized. The objective of this study was to elucidate the global incidence of surgically relevant CNS infection, highlighting geographic areas for targeted improvement in neurosurgical capacity.
METHODS
A systematic literature review and meta-analysis were performed to capture studies published between 1990 and 2016. PubMed, EMBASE, and Cochrane databases were searched using variations of terms relating to CNS infection and epidemiology (incidence, prevalence, burden, case fatality, etc.). To deliver a geographic breakdown of disease, results were pooled using the random-effects model and stratified by WHO region and national income status for the different CNS infection types.
RESULTS
The search yielded 10,906 studies, 154 of which were used in the final qualitative analysis. A meta-analysis was performed to compute disease incidence by using data extracted from 71 of the 154 studies. The remaining 83 studies were excluded from the quantitative analysis because they did not report incidence. A total of 508,078 cases of CNS infections across all studies were included, with a total sample size of 130,681,681 individuals. Mean patient age was 35.8 years (range: newborn to 95 years), and the male/female ratio was 1:1.74. Among the 71 studies with incidence data, 39 were based in high-income countries, 25 in middle-income countries, and 7 in low-income countries. The pooled incidence of studied CNS infections was consistently highest in low-income countries, followed by middle- and then high-income countries. Regarding WHO regions, Africa had the highest pooled incidence of bacterial meningitis (65 cases/100,000 people), neurocysticercosis (650/100,000), and tuberculous spondylodiscitis (55/100,000), whereas Southeast Asia had the highest pooled incidence of intracranial abscess (49/100,000), and Europe had the highest pooled incidence of nontuberculous vertebral spondylodiscitis (5/100,000). Overall, few articles reported data on deaths associated with infection. The limited case fatality data revealed the highest case fatality for tuberculous meningitis/spondylodiscitis (21.1%) and the lowest for neurocysticercosis (5.5%). In all five disease categories, funnel plots assessing for publication bias were asymmetrical and suggested that the results may underestimate the incidence of disease.
CONCLUSIONS
This systematic review and meta-analysis approximates the global incidence of neurosurgically relevant infectious diseases. These results underscore the disproportionate burden of CNS infections in the developing world, where there is a tremendous demand to provide training and resources for high-quality neurosurgical care.
Background:
Liver transplant recipients (LTR) who are seropositive for cytomegalovirus (CMV) (R+) are at intermediate-risk for CMV disease. A preventive strategy following transplant is considered standard of care. Current guidelines recommend high-dose valganciclovir (VGCV) (900 mg/day adjusted for renal function) for prophylaxis given limited data on the efficacy and safety of low-dose VGCV (450 mg/day adjusted for renal function). We describe our experience using low-dose VGCV prophylaxis for R+ LTR at our institution.
Methods:
A single-center, retrospective study was conducted using a database of 364 LTR over a four-year period (2011-2014). Adult first-time R+ LTR receiving low-dose VGCV prophylaxis were included. The primary endpoint was CMV disease at one-year post-transplant. Patients were compared to historical controls receiving high-dose VGCV prophylaxis. Secondary endpoints were biopsy-proven rejection and leukopenia on VGCV. With respect to leukopenia, patients receiving low-dose VGCV were compared to a group of D+R- patients from the database receiving high-dose VGCV. Univariable analyses were performed using chi-squared, Fisher's exact, and Wilcoxon rank-sum tests.
Results:
A total of 200 R+ LTR met inclusion criteria. Median age was 60 (interquartile range [IQR], 54-66) years, and 129 (65%) LTR were male. Median MELD score was 22 (IQR, 14-31) and 178 (89%) patients received deceased-donor transplants. CMV disease occurred in only 9 (5%) patients, similar to rates in previous studies of LTR receiving high-dose VGCV. Biopsy-proven rejection occurred in 18 (9%) patients. Patients received VGCV prophylaxis for a median 3.4 (IQR, 3.1-4.3) months. 151 (76%) R+ LTR receiving low-dose VGCV developed leukopenia. Premature VGCV discontinuation and G-CSF use were infrequent and not significantly different between the two groups.
Conclusion:
Low-dose VGCV was safe and effective for prevention of CMV disease in our cohort of 200 R+ LTR and should be considered as an option in future guidelines. This article is protected by copyright. All rights reserved.
Several studies have determined that Bacterial Meningitis Score (BMS) has a high sensitivity and specificity for distinguishing bacterial meningitis from aseptic meningitis. Thus, the authors conducted a cross-sectional study in 252 children with clinical suspected meningitis in the Hatyai Hospital located in the Southern part of Thailand. In this study, BMS has 100% sensitivity (95%CI; 0.799-1) and 62.1% specificity (95%CI; 0.554-0.682). Positive predictive value(PPV) was 18.5% (95%CI;0.119-0.273) and negative predictive value(NPV) was 100% (95%CI; 0.967-1). BMS is a useful screening tool for early diagnosis of bacterial meningitis before cerebrospinal fluid culture result is known, especially when latex agglutination is not available. BMS is not recommended as a diagnostic confirmation tool because of its low specificity.
The cytologic evaluation of exfoliative and fine needle aspiration material is one of the most widely used diagnostic modalities worldwide. Now thoroughly updated with new guidelines and references, and featuring more than 1000 high-quality color photomicrographs, Differential Diagnosis in Cytopathology remains the essential organ-based reference guide for practising and trainee pathologists and cytotechnologists. This new edition addresses a comprehensive variety of benign and malignant neoplastic conditions, utilizing a consistent structure with bullet-point text for quick access and assimilation. The full spectrum of infectious and inflammatory disorders are also presented in detail. The information is not limited to light microscopic findings but includes many other genetic, molecular, and immunologic diagnostic modalities, giving readers the diagnostic and clinical criteria needed when formulating a diagnosis and differential diagnosis. No other book focuses exclusively on essential diagnostic criteria, making this an essential text for pathologists, cytopathologists and cytotechnologists at all stages of their careers.
Background & objectives:
Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance.
Methods:
Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per μl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens.
Results:
A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively).
Interpretation & conclusions:
Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.
More than 2·3 million children died in India in 2005; however, the major causes of death have not been measured in the country. We investigated the causes of neonatal and child mortality in India and their differences by sex and region.
The Registrar General of India surveyed all deaths occurring in 2001-03 in 1·1 million nationally representative homes. Field staff interviewed household members and completed standard questions about events that preceded the death. Two of 130 physicians then independently assigned a cause to each death. Cause-specific mortality rates for 2005 were calculated nationally and for the six regions by combining the recorded proportions for each cause in the neonatal deaths and deaths at ages 1-59 months in the study with population and death totals from the United Nations.
There were 10,892 deaths in neonates and 12,260 in children aged 1-59 months in the study. When these details were projected nationally, three causes accounted for 78% (0·79 million of 1·01 million) of all neonatal deaths: prematurity and low birthweight (0·33 million, 99% CI 0·31 million to 0·35 million), neonatal infections (0·27 million, 0·25 million to 0·29 million), and birth asphyxia and birth trauma (0·19 million, 0·18 million to 0·21 million). Two causes accounted for 50% (0·67 million of 1·34 million) of all deaths at 1-59 months: pneumonia (0·37 million, 0·35 million to 0·39 million) and diarrhoeal diseases (0·30 million, 0·28 million to 0·32 million). In children aged 1-59 months, girls in central India had a five-times higher mortality rate (per 1000 livebirths) from pneumonia (20·9, 19·4-22·6) than did boys in south India (4·1, 3·0-5·6) and four-times higher mortality rate from diarrhoeal disease (17·7, 16·2-19·3) than did boys in west India (4·1, 3·0-5·5).
Five avoidable causes accounted for nearly 1·5 million child deaths in India in 2005, with substantial differences between regions and sexes. Expanded neonatal and intrapartum care, case management of diarrhoea and pneumonia, and addition of new vaccines to immunisation programmes could substantially reduce child deaths in India.
US National Institutes of Health, International Development Research Centre, Canadian Institutes of Health Research, Li Ka Shing Knowledge Institute, and US Fund for UNICEF.
Meningitis continues to be a formidable illness with high morbidity and mortality among children in India. The present study was undertaken to prospectively look for the prevalence of pyogenic meningitis at Gulbarga and to find out the utility of gram stain, Latex Agglutination Test and (LTA) and C-reactive protein in the rapid diagnosis of pyogenic meningitis from children. Over a 48-months period, 535 children with a presumptive clinical diagnosis of acute bacterial meningitis were investigated by direct microscopy, CRP, bacterial culture, latex agglutination test (L TA), cell count and cell type and biochemical tests. Latex Agglutination Test (LA T) was done for detection of the antigens of Streptococcus pneumoniae, Group B Streptococci, E. coli, Neisseria meningitidis and Haemophilus influenzae type b. Among 535 suspected meningitis cases, 291 cases were diagnosed as pyogenic meningitis cases based on biochemical tests, cell count and cell type. Out of 291 cases, 55 cases have already received antibiotic treatment. Among 236 cases of untreated pyogenic meningitis cases, 199 CSF samples were culture positive. Streptococcus pneumoniae (44.7%) was the predominant organism identified, followed by H influenzae (25.6%) and Gp. B. Streptococci (9.5%). 208 of 236 cases were gram-stain positive, 129 cases had elevated CSF-CRP and 214 cases were diagnosed as pyogenic meningitis by the detection of bacterial antigens by latex agglutination test. Among 55 pretreated cases, only 05 (9.1%) CSF samples were culture positive, bacteria was observed in 36 gram stain smear, CRP was elevated in 16 CSF samples and 52 pretreated cases of suspected meningitis were diagnosed as pyogenic meningitis by latex agglutination test for detection of bacterial antigens. Many of the bacterial isolates were sensitive to gentamicin, cefotaxime and ceftriaxone and least sensitive to tetracycline and gentamicin. 13.1% of gram-negative bacilli were ESBL producers. To conclude, inclusion of latex agglutination test for detection of bacterial antigen in the routine diagnosis adds a valuable adjunct in the rapid and accurate diagnosis of pyogenic meningitis.
* Young infants who have meningitis may present with nonspecific clinical manifestations. * S. pneumoniae and N. meningitidis remain the most common causes of bacterial meningitis in the infant and child, and GBS continues to be the most common neonatal pathogen. * Empiric therapy for suspected bacterial meningitis in a non-neonate includes a combination of parenteral vancomycin and either cefotaxime or ceftriaxone. * Children whose GCS scores are less than 8, show signs of shock or respiratory compromise, and have focal neurologic findings or clinical signs of elevated intracranial pressure should be admitted to a pediatric intensive care unit. * Sensorineural hearing loss occurs in 30% of children who have pneumococcal and 10% of those who have meningococcal meningitis.
The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis.
We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture.
We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with >or=12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for <12 hours, had significantly higher median cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median cerebrospinal fluid protein levels (121 vs 178 mg/dL).
In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.
To estimate frequency of acute bacterial meningitis (ABM) in early childhood in hospital admissions, to describe clinical and diagnostic features, and to analyze mortality, complications and long term sequelae.
Prospective study.
Pediatric wards and Rehabilitation Center of KEM Hospital, Pune.
Study subjects between the ages of 1 months to 5 years with ABM were recruited. Clinical details were recorded. CSF was analysed by routine biochemical methods, antigen detection tests (Latex agglutination LAT) and microbiological studies on special media. Management was as per standard protocols. Survivors were followed up long term with neurodevelopmental studies and rehabilitation programmes.
In a study period of 2 years, 54 children (1.5% of all admissions) satisfied the criteria of ABM in early childhood; 78% were below one year and 52% were under the age of six months. Chief presentation was high fever, refusal of feeds, altered sensorium and seizures. Meningeal signs were present in only 26%. CSF C-reactive protein was positive in 41%, gram stain was positive in 67% LAT in 78% and cultures grew causative organisms in 50% of the cases. The final etiological diagnosis (as per LAT and/or cultures) were Streptococcus pneumoniae 39% Hemophilus influenzae type b 26% and others in 35% The others included one case of Neisseria meningitidis and 10 who were LAT negative and culture sterile. 39% patients developed acute neurological complications during the hospital course. 31% children with ABM died in hospital or at home soon after discharge. Six were lost to follow up. Of the 31 children, available for long term follow up (1-3 years), 14 (45%) had no sequelae. The remaining had significant neurodevelopmental handicaps ranging from isolated hearing loss to severe mental retardation with multiple disabilities.
ABM in early childhood has a considerable mortality, morbidity and serious long term sequelae. Neurodevelopmental follow up and therapy should begin early. Etiological diagnosis can be enhanced by LAT and good culture media. H. influenzae b and S. pneumoniae account for more than 60% of ABM in early childhood.
Lumbar puncture is frequently performed in primary care. Properly interpreted tests can make cerebrospinal fluid (CSF) a key tool in the diagnosis of a variety of diseases. Proper evaluation of CSF depends on knowing which tests to order, normal ranges for the patient's age, and the test's limitations. Protein level, opening pressure, and CSF-to-serum glucose ratio vary with age. Xanthochromia is most often caused by the presence of blood, but several other conditions should be considered. The presence of blood can be a reliable predictor of subarachnoid hemorrhage but takes several hours to develop. The three-tube method, commonly used to rule out a central nervous system hemorrhage after a "traumatic tap," is not completely reliable. Red blood cells in CSF caused by a traumatic tap or a subarachnoid hemorrhage artificially increase the white blood cell count and protein level, thereby confounding the diagnosis. Diagnostic uncertainty can be decreased by using accepted corrective formulas. White blood cell differential may be misleading early in the course of meningitis, because more than 10 percent of cases with bacterial infection will have an initial lymphocytic predominance and viral meningitis may initially be dominated by neutrophils. Culture is the gold standard for determining the causative organism in meningitis. However, polymerase chain reaction is much faster and more sensitive in some circumstances. Latex agglutination, with high sensitivity but low specificity, may have a role in managing partially treated meningitis. To prove herpetic, cryptococcal, or tubercular infection, special staining techniques or collection methods may be required.
Children with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. We previously developed a clinical prediction rule, the Bacterial Meningitis Score, that classifies patients at very low risk of bacterial meningitis if they lack all of the following criteria: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1000 cells/microL, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/microL, and a history of seizure before or at the time of presentation.
To validate the Bacterial Meningitis Score in the era of widespread pneumococcal conjugate vaccination.
A multicenter, retrospective cohort study conducted in emergency departments of 20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. All children aged 29 days to 19 years who presented at participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells > or =10 cells/microL) and who had not received antibiotic treatment before lumbar puncture.
The sensitivity and negative predictive value of the Bacterial Meningitis Score.
Among 3295 patients with CSF pleocytosis, 121 (3.7%; 95% confidence interval [CI], 3.1%-4.4%) had bacterial meningitis and 3174 (96.3%; 95% CI, 95.5%-96.9%) had aseptic meningitis. Of the 1714 patients categorized as very low risk for bacterial meningitis by the Bacterial Meningitis Score, only 2 had bacterial meningitis (sensitivity, 98.3%; 95% CI, 94.2%-99.8%; negative predictive value, 99.9%; 95% CI, 99.6%-100%), and both were younger than 2 months old. A total of 2518 patients (80%) with aseptic meningitis were hospitalized.
This large multicenter study validates the Bacterial Meningitis Score prediction rule in the era of conjugate pneumococcal vaccine as an accurate decision support tool. The risk of bacterial meningitis is very low (0.1%) in patients with none of the criteria. The Bacterial Meningitis Score may be helpful to guide clinical decision making for the management of children presenting to emergency departments with CSF pleocytosis.
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.
It has been suggested Haemophilus influenzae serotype b (Hib) disease is uncommon in Asia. During 1993-1997, we conducted prospective surveillance of acute infections caused by H. influenzae in 6 academic referral Indian hospitals. The study included 5798 patients aged 1 month to 50 years who had diseases likely to be caused by H. influenzae; 75% of the patients were aged <5 years. A total of 125 H. influenzae infections were detected, 97% of which were caused by Hib. Of 125 isolates, 108 (86%) were from children aged <5 years, and 11 (9%) were from adults aged >18 years. Sixty-two percent of the patients had meningitis. The case-fatality rate was 11% overall and 20% in infants with Hib meningitis. Up to 60% of all isolates were resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, or erythromycin; 32% were resistant to ≥3 antimicrobial drugs, but none were resistant to third-generation cephalosporins. These data suggest that available Hib vaccines will benefit Indian children.
Background
Although Streptococcus pneumoniae is recognised as an important cause of morbidity and mortality worldwide, in India few data are available on the pattern of invasive disease, serogroup/type prevalence, and antimicrobial susceptibility pattem of the organism.
Methods
We studied the characteristics of invasive pneumococcal infections in six hospitals in India over 4 years, in patients with suspected pneumonia (3686), pyogenic meningitis (1107), septicaemia (257), or localised pus-forming lesions (688). Blood, cerebrospinal fluid (CSF), or other normally sterile body fluids were cultured, and CSF was tested for pneumococcal antigens. All pneumococcal isolates were serotyped and their antimicrobial susceptibility tested by standard methods.
Findings
S pneumoniae was isolated from blood, other normally sterile body fluids, or deep-seated pus in 307 patients, and antigen was detected in CSF in a further seven. 71 patients were younger than 2·0 years, 32 were 2·0–4·9 years, and 211 were older than 5·0 years. The clinical syndromes associated with pneumococcal infection were meningitis (117; case-fatality rate 34%), pneumonia (93; 19%), septicaemia (24; 21%), peritonitis (23; 4%), and others (empyema thoracis, pericarditis, or arthritis 57; 6%). Overall, 215 (70%) of the isolates were of serotypes 1, 6, 19, 7, 5, 15, 14, 4, 16, and 18 (in order of frequency). The most common serotypes in children under 5 years were 6, 1, 19, 14, 4, 5, 45, 12, and 7. Serotypes 1 and 5 accounted for 29% (92 of 314) of disease. Intermediate resistance to penicillin was noted in only four (1·3%) isolates; however, resistance to cotrimoxazole (trimethoprim-sulphamethoxazole) and chloramphenicol was seen in 173 (56%) and 51 (17%) isolates, respectively.
Interpretation
Hospital-based surveillance of communityacquired infections can provide data useful for planning. Two pneumococcol serotypes accounted for a significant proportion of the disease. Although penicillin resistance was infrequently present, continued surveillance will be prudent.
As reviewed in this paper, meningococcal disease epidemiology varies substantially by geographic area and time. The disease can occur as sporadic cases, outbreaks, and large epidemics. Surveillance is crucial for understanding meningococcal disease epidemiology, as well as the need for and impact of vaccination. Despite limited data from some regions of the world and constant change, current meningococcal disease epidemiology can be summarized by region. By far the highest incidence of meningococcal disease occurs in the meningitis belt of sub-Saharan Africa. During epidemics, the incidence can approach 1000 per 100,000, or 1% of the population. Serogroup A has been the most important serogroup in this region. However, serogroup C disease has also occurred, as has serogroup X disease and, most recently, serogroup W-135 disease. In the Americas, the reported incidence of disease, in the range of 0.3-4 cases per 100,000 population, is much lower than in the meningitis belt. In addition, in some countries such as the United States, the incidence is at an historical low. The bulk of the disease in the Americas is caused by serogroups C and B, although serogroup Y causes a substantial proportion of infections in some countries and W-135 is becoming increasingly problematic as well. The majority of meningococcal disease in European countries, which ranges in incidence from 0.2 to 14 cases per 100,000, is caused by serogroup B strains, particularly in countries that have introduced serogroup C meningococcal conjugate vaccines. Serogroup B also predominates in Australia and New Zealand, in Australia because of the control of serogroup C disease through vaccination and in New Zealand because of a serogroup B epidemic. Based on limited data, most disease in Asia is caused by serogroup A and C strains. Although this review summarizes the current status of meningococcal disease epidemiology, the dynamic nature of this disease requires ongoing surveillance both to provide data for vaccine formulation and vaccine policy and to monitor the impact of vaccines following introduction.
Clinical diagnosis of pediatric meningitis is fundamental; therefore, familiarity with evidence underscoring clinical features suggestive of meningitis is important.
To seek evidence supporting accuracy of clinical features of pediatric bacterial meningitis.
A review of Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed was conducted for all articles of relevance. Articles contained prospective data of clinical features in children with laboratory-confirmed bacterial meningitis and in comparison groups of those without it. Two authors independently assessed quality and extracted data to calculate accuracy data of clinical features.
Of 14 145 references initially identified, 10 met our inclusion criteria. On history, a report of bulging fontanel (likelihood ratio [LR]: 8.00 [95% confidence interval (CI): 2.4-26]), neck stiffness (7.70 [3.2-19]), seizures (outside febrile-convulsion age range) (4.40 [3.0-6.4]), or reduced feeds (2.00 [1.2-3.4]) raised concern about the presence of meningitis. On examination, jaundice (LR: 5.90 [95% CI: 1.8-19]), being toxic or moribund (5.80 [3.0-11]), meningeal signs (4.50 [2.4-8.3]), neck stiffness (4.00 [2.6-6.3]), bulging fontanel (3.50 [2.0-6.0]), Kernig sign (3.50 [2.1-5.7]), tone up (3.20 [2.2-4.5]), fever of >40°C (2.90 [1.6-5.5]), and Brudzinski sign (2.50 [1.8-3.6]) independently raised the likelihood of meningitis. The absence of meningeal signs (LR: 0.41 [95% CI: 0.30-0.57]) and an abnormal cry (0.30 [0.16-0.57]) independently lowered the likelihood of meningitis. The absence of fever did not rule out meningitis (LR: 0.70 [95% CI: 0.53-0.92]).
Evidence for several useful clinical features that influence the likelihood of pediatric meningitis exists. No isolated clinical feature is diagnostic, and the most accurate diagnostic combination is unclear.
Numerous sequelae have been noted in survivors of bacterial meningitis; however, few studies document sequelae for several years following a childhood episode of bacterial meningitis. In addition, studies generally focus on the more commonly found sequelae. To review the known information and highlight this gap, this article presents a comprehensive literature review of the long-term (≥ 5 years of follow-up) sequelae of childhood bacterial meningitis.
A systematic literature search was conducted between December 2009 and February 2010. English-language articles published between January 1970 and January 2010 were selected for screening. Articles were included if the subjects were between the ages of 1 month and <18 years at the time of diagnoses of meningitis.
A total of 1433 children who were survivors of childhood bacterial meningitis were evaluated for sequelae after the time of discharge. Of these children, 705 (49.2%) were reported to have 1 or more long-term sequelae. A majority of reported sequelae were behavioral and/or intellectual disorders (n 455, 45.0%). Hearing changes accounted for 6.7% (n 68) of sequelae and gross neurologic deficits accounted for 14.3% (n 145).
A majority of childhood bacterial meningitis survivors with long-term sequelae that are documented in the literature have academic and behavioral limitations. While neurologic deficits may resolve over time, subtle behavioral deficits may not be appreciated initially and may continue to affect survivors for many years. Further studies are needed to quantify the true societal and economic burden of long-term sequelae as well as fully understand the breadth of types of sequelae that survivors experience.
Up-to-date information on the causes of child deaths is crucial to guide global efforts to improve child survival. We report new estimates for 2008 of the major causes of death in children younger than 5 years.
We used multicause proportionate mortality models to estimate deaths in neonates aged 0-27 days and children aged 1-59 months, and selected single-cause disease models and analysis of vital registration data when available to estimate causes of child deaths. New data from China and India permitted national data to be used for these countries instead of predictions based on global statistical models, as was done previously. We estimated proportional causes of death for 193 countries, and by application of these proportions to the country-specific mortality rates in children younger than 5 years and birth rates, the numbers of deaths by cause were calculated for countries, regions, and the world.
Of the estimated 8.795 million deaths in children younger than 5 years worldwide in 2008, infectious diseases caused 68% (5.970 million), with the largest percentages due to pneumonia (18%, 1.575 million, uncertainty range [UR] 1.046 million-1.874 million), diarrhoea (15%, 1.336 million, 0.822 million-2.004 million), and malaria (8%, 0.732 million, 0.601 million-0.851 million). 41% (3.575 million) of deaths occurred in neonates, and the most important single causes were preterm birth complications (12%, 1.033 million, UR 0.717 million-1.216 million), birth asphyxia (9%, 0.814 million, 0.563 million-0.997 million), sepsis (6%, 0.521 million, 0.356 million-0.735 million), and pneumonia (4%, 0.386 million, 0.264 million-0.545 million). 49% (4.294 million) of child deaths occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan, and China.
These country-specific estimates of the major causes of child deaths should help to focus national programmes and donor assistance. Achievement of Millennium Development Goal 4, to reduce child mortality by two-thirds, is only possible if the high numbers of deaths are addressed by maternal, newborn, and child health interventions.
WHO, UNICEF, and Bill & Melinda Gates Foundation.
Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities.
We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years.
We calculated that Hib caused about 8.13 million serious illnesses worldwide in 2000 (uncertainty range 7.33-13.2 million). We estimated that Hib caused 371,000 deaths (247,000-527,000) in children aged 1-59 months, of which 8100 (5600-10,000) were in HIV-positive and 363,000 (242,000-517,000) in HIV-negative children.
Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality.
GAVI Alliance and the Vaccine Fund.
Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years.
We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b.
In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449,000 [316,000-501,000]) occurred in ten African and Asian countries.
S pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden.
GAVI Alliance and the Vaccine Fund.
Acute bacterial meningitis (ABM) is a rapidly developing acute inflammation of leptomeninges and underlying subarachnoid cerebrospinal fluid (CSF). ABM is caused by bacteria and has a case fatality rate of 20-30%. Most prevalent causes of ABM are Neisseria meningitis, Streptococcus pneumoniae and Haemophilus influenzae. The aim of this paper is to summarize the main findings from Cochrane systematic reviews that have considered the evidence for treatments of ABM.
We searched the Cochrane Library (issue 1, 2007) for relevant reviews using 'meningitis' as a search term. The titles of all the search results were examined to select reviews on treatment of ABM. The full text of each of the selected reviews was studied to summarize the evidence available in Cochrane systematic reviews.
We found three Cochrane reviews that focused specifically on the treatment of ABM, addressing empiric antibiotic therapy, fluid therapy and effects of adjuvant corticosteroids respectively. No statistically significant difference was found between third generation cephalosporins and conventional antibiotics in the combined endpoint of death or deafness (risk difference (RD) -1%, 95% CI -4% to +2%). However, culture positivity of CSF at 10-48 h was significantly higher in the conventional antibiotic group and diarrhoea was significantly more common in the cephalosporin group. When third generation cephalosporins are not available, ampicillin-chloramphenicol combination may be used as an alternative empiric treatment, however both resistance pattern as well as availability should be considered while prescribing empiric therapy of community acquired ABM. The fluid therapy review found too few studies to provide any robust conclusion. In settings with high mortality rates and where patients present late, use of intravenous maintenance fluids seems preferable to a restricted fluid intake. The efficacy of adjuvant corticosteroids varied between high- and low-income countries suggesting greater mortality reduction in high-income countries (RR 0.74, 95% CI 0.52-1.05) than in low-income countries (RR 0.87, 95% CI 0.72-1.05) and a beneficial effect on severe hearing loss in high-income countries (RR 0.32, 95% CI 0.18-0.57), whereas, sparse data in low-income countries (RR 1.04, 95% CI 0.66-1.63). A four-day regimen of dexamethasone should be given preferably before or with the first dose of antibiotics for cases of ABM from high-income countries.
In presence of sensitive organisms, third generation cephalosporins and conventional antibiotics lead to similar outcomes. More studies are needed to determine the antimicrobial resistance pattern against various antibiotics in rural and remote areas of developing as well as developed countries. To assess the effectiveness of either restricting or maintenance fluids in populations where patients present early and on death and disability when mortality rates are low, large trials should be conducted. More trials are needed to assess the use of adjuvant dexamethasone for ABM in low-income countries.
To know the usefulness of Latex Agglutination Test (LAT) for the diagnosis of bacterial meningitis (BM), it was performed in all the 114 consecutive samples of CSF with polymorphs from 114 prospectively recruited children aged 2 months to 11 years. Definite diagnosis of BM based on culture and/or LAT was evident in 55. Among the 46 LAT positive, culture was positive in 3 only. Major organisms identified by LAT were H. influenzae B (HiB) in 28 and S. pneumoniae (SP) in 15. Ninety per cent of HiB and 67% of SP bacterial meningitis were under one year of age. Fever > 7 days prior to admission was not uncommon (38%) and 26% had received prior antibiotics. Meningeal signs were present in 64%. CSF cells were < 500/mm3 in 24% and sugar was > 50% of blood level in 23%. There was no significant difference in the immediate outcome between HiB and SP meningitis. The case fatality was 22% and was significantly high in cases who had altered level of consciousness on admission (p = 0.02). It is concluded that LAT is very useful for rapid diagnosis of BM.
Aseptic meningitis is often reported to be characterized by a mononuclear cell predominance in the cerebrospinal fluid (CSF), whereas bacterial meningitis is characterized by a polymorphonuclear (PMN) cell predominance. In contrast, other studies suggest that PMNs can be the most prevalent cell in early aseptic meningitis followed by a shift to mononuclear cells within 24 hours. These contradictory reports may lead to uncertainty in the diagnosis and treatment of meningitis.
To assess 1) the characteristics of the CSF differential in aseptic versus bacterial meningitis, 2) the influence of duration of illness on the CSF differential, and 3) the role of the CSF differential in discriminating between aseptic versus bacterial meningitis.
A retrospective chart review was conducted of all cases of meningitis in children >30 days of age hospitalized during the peak months for enteroviral meningitis (April to October) between 1992 to 1997. Cases of aseptic meningitis were defined as having at least 20 white blood cells/mm(3) and the absence of bacterial growth on culture. Patients were excluded if they received antibiotic therapy within the previous 5 days. Cases of bacterial meningitis were defined as having a positive culture of the CSF or the presence of a CSF pleocytosis with positive cultures of the blood. CSF variables including white blood cell differential and time from the onset of symptoms to the performance of a lumbar puncture were analyzed. PMNs were considered to be predominant when the percentage of neutrophils added to juvenile forms was >50% of cells.
One hundred fifty-eight cases of meningitis were reviewed: 138 were aseptic and 20 were bacterial. The patients ranged in age from 30 days to 18 years; 61% were male. Fifty-seven percent of cases of aseptic meningitis had a PMN predominance. The percentage of PMNs in the CSF in patients with aseptic meningitis was not statistically different for patients who had a lumbar puncture performed either within or beyond 24 hours of the onset of symptoms. Fifty-one percent of the 53 patients with aseptic meningitis and duration of illness >24 hours had a PMN predominance. The ability of a PMN predominance to differentiate between aseptic and bacterial meningitis was assessed. The sensitivity of a PMN predominance for aseptic meningitis is 57% whereas the specificity is 10%. The positive predictive value of a PMN predominance for aseptic disease is 81% but the negative predictive value is 3%. Alternative definitions of PMN predominance from 60% to 90% were not useful as a clinical indicator of bacterial disease.
The majority of children with aseptic meningitis have a PMN predominance in the CSF. The PMN predominance is not limited to the first 24 hours of illness. Because the majority of children with a PMN predominance during enteroviral season will have aseptic disease, a PMN predominance as a sole criterion does not discriminate between aseptic and bacterial meningitis.
Bacterial meningitis is an important cause of childhood morbidity and mortality world-wide. In the developing world, where the burden of acute meningitis and its long-term sequelae are especially high, staff with limited training at primary health care facilities must be able to recognize the symptoms and signs of meningitis, so that suspected cases can be referred urgently to hospitals.
Children who presented with possible invasive bacterial infection to health facilities in The Gambia, West Africa, between 1993 and 1995 were investigated in a standardized manner and clinical findings were documented. Bacterial meningitis was defined as the growth of bacteria from the cerebrospinal fluid. Clinical findings were compared between cases of meningitis and other children.
Of 2097 children between 2 months and 3 years of age investigated, 51 had a confirmed diagnosis of bacterial meningitis. In multivariate analysis using a model adjusting for age but not including respiratory signs, the variables associated independently with meningitis were appearance of being very sick (odds ratio for meningitis vs. no meningitis or no lumbar puncture performed (OR) 4.1, 95% CI 1.5-11.1), being lethargic or unconscious (OR 5.2, 95% CI 2.1-13), a stiff neck (OR 29.3, 95% CI 12.2-70.3), a bulging fontanel (OR 3.2, 95% CI 1.2-8.5) and reduced feeding as a prompted complaint (OR 2.9, 95% CI 1.3-6.7). A combination model of a history of convulsions, or being lethargic or unconscious, or having a stiff neck, as used in the WHO-Integrated Management of Childhood Illness (IMCI) guidelines, had a sensitivity of 98% and a specificity of 72% to predict meningitis.
A combination of a limited number of signs is sufficient to predict meningitis with high sensitivity, without a large number of children who do not have meningitis being unnecessarily referred.
A polymerase chain reaction (PCR) for detecting Hib in cerebrospinal fluid (CSF) was evaluated and compared with culture and a latex agglutination test (LAT) in a hospital-based prospective surveillance. We studied 107 children aged from 1 month to 12 years with a clinical and CSF profile suggestive of acute bacterial meningitis. CSF culture was performed on blood-chocolate agar by standard technique, LAT by a commercially available kit (Wellcogen) and PCR using total DNA extracted from CSF samples. Of 107 children, 79% had received one or more doses of injectable antibiotics. Hib was detected by culture in 14 cases, by LAT in 23 and by PCR in 37. All CSF samples that reveal Hib by culture or LAT had a PCR positive for Hib (sensitivity 100%). PCR also detected 14 additional cases of Hib meningitis which were not detected by culture or LAT. We conclude that PCR is a sensitive and specific diagnostic tool that may be valuable in a population with high pre-hospital antibiotic usage.
To define central nervous system infections of infants and children that occur as co-morbid or predisposing conditions of sepsis.
Standard pediatric infectious disease references and the pertinent literature in English were reviewed from 1960 to 2002 to ascertain the previous methods and definitions utilized in clinical studies of the epidemiology and treatment of bacterial infections of the central nervous system. An accepted definition of bacterial meningitis defined by the Infectious Disease Society of America was reviewed and adapted to the previous clinical definitions. The information was formulated into a proposed standard for definite, probable, and possible bacterial infections of the central nervous system.
The diagnosis of definite bacterial infection of the central nervous system, including bacterial meningitis, requires the isolation of the pathogen from the cerebrospinal fluid or other significant clinical site such as surgical tissue, an implanted device, or blood. Probable bacterial infection is defined by the association of a compatible clinical syndrome or cerebrospinal fluid changes associated with bacterial meningitis or other central nervous system infection, and confirmed as an anatomically defined infection by imaging or surgery, in association with positive blood cultures or bacterial antigen from cerebrospinal fluid. Possible bacterial meningitis may be defined as a compatible clinical syndrome with predefined cerebrospinal fluid changes in the absence of a confirmatory culture or antigen test from any site.
Bacterial meningitis and other central nervous system bacterial infections can be defined as definite, probable, and possible with a combination of a defining compatible clinical syndrome and an anatomic definition by surgery or imaging, coupled with isolation of the organism, bacterial antigen, or other defining molecular component of the organism.
To highlight some of the recent key epidemiologic and clinical diagnostic dilemmas of aseptic meningitis and to evaluate some tests that may help distinguish aseptic compared with bacterial meningitis.
Enteroviruses remain the most common cause of aseptic meningitis. Certain enteroviruses (e.g. coxsackie B5, echovirus 6, 9 and 30) are more likely to cause meningitis outbreaks, while others (coxsackie A9, B3 and B4) are mostly endemic. Nucleic acid tests are more sensitive than cultures in diagnosing enteroviral infections. In centers where the turnaround time for these tests is less than 24 h, there can be substantial cost savings and avoidance of unnecessary treatment of aseptic meningitis with antibiotics. Serum and stool specimens are important adjunct samples for diagnosing enteroviral infections in children. Cerebrospinal fluid protein (> or = 0.5 g/l) and serum procalcitonin (> or = 0.5 ng/ml) appear to be useful laboratory markers for distinguishing between bacterial and aseptic meningitis in children aged 28 days to 16 years, but they have relatively low sensitivity and specificity.
Enteroviruses are the major causes of aseptic meningitis. The major focus of diagnosis remains ruling out bacterial infection or confirming enteroviral etiology of infection. Properly implemented nucleic acid tests have the potential to reduce cost and unnecessary treatment.
Handbook: IMCI integrated management of childhood illness. Department of Child and Adolescent Health and Develop-ment
- Who
- Unicef
WHO/UNICEF. Handbook: IMCI integrated management of childhood illness. Department of Child and Adolescent Health and Develop-ment, 2005.
as well as the members of the Bacterial Meningitis Surveillance Working Group at All India Institute of Medical Sciences
- Dr Saradha
- Suresh
- Mohamed Dr
- Meeran
- G S Ms
- Chamundeeswari
Dr Saradha Suresh, Dr Mohamed Meeran, Ms G. S. Chamundeeswari, as well as the members of the Bacterial Meningitis Surveillance Working Group at All India Institute of Medical Sciences (New Delhi), Chhatrapati Shahuji Maharaj Medical University (Lucknow, Uttar Pradesh), Christian Medical College (Vellore, Tamil Nadu), INCLEN Trust In-ternational (Lucknow, Uttar Pradesh), and Kalawati Saran Children's Hospital (New Delhi).
Global, regional, and national causes of child mortality in 2008: a systematic analysis
- Black
WHO global database on child growth and malnutrition. WHO/NUT/97.4: World Health Organization, Department of Nutrition for Health and Development
- M De Onis
- M Blössner