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Bacterial meningitis score accurately predicts which children are at low risk
CURRENT BEST EVIDENCE
Clinical Research Abstracts for Pediatricians EDITOR’S NOTE: Journals reviewed for this issue: Archives of Disease in Childhood, Archives of Pediatrics and Adolescent Medicine, British Medical Journal, Journal of the American Medical Association, Journal of Pediatrics, The Lancet, New England Journal of Medicine, Pediatric Infectious Diseases Journal, and Pediatrics. Gurpreet K. Rana, B.Sc., M.L.I.S, Taubman Medical Library, University of Michigan, contributed to the review and selection of this month’s abstracts. —John G. Frohna, MD, MPH
Bacterial meningitis score accurately predicts which children are at low risk Nigrovic LE, Kuppermann N, Macias CG, Cannavino CR, Moro-Sutherland DM, Schremmer RD, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA 2007;297:52-60. Given the widespread use of pneumococcal conjugate vaccine, does the Bacterial Meningitis Score predict which children are at very low risk of bacterial meningitis?
Question
Context Children with cerebrospinal fluid (CSF) pleocyto-
sis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. Design Multicenter, retrospective cohort study. The authors previously developed a clinical prediction rule, the Bacterial Meningitis Score, based on five predictors: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1,000 cells/L, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/L, and a history of seizure before or at the time of presentation. In the current study, patients lacking any of these predictors are classified as low risk.
20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Setting
All children aged 29 days to 19 years who presented to participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells ⱖ10 cells/L) and who had not received antibiotic treatment before lumbar puncture.
Participants
The sensitivity and negative predictive value of the Bacterial Meningitis Score.
Outcome
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%-
Main Results
Clinical Research Abstracts for Pediatricians
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. Conclusions 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. Commentary Meningitis is the most feared infectious entity among febrile infants and children presenting to emergency departments. Studies of clinical diagnosis have not identified reliable criteria for distinguishing between bacterial and viral etiologies.1 The decline in incidence of bacterial meningitis with the advent of effective vaccines against S. pneumoniae and H. influenzae b has heightened the potential value of such criteria in avoiding unnecessary admissions and treatment. Nigrovic, et al’s validation of their previously derived prediction rule is a welcome adjunct to clinical decision making. Their new retrospective study involves an acceptable simplification of the original rule which required calculation of a point score.2 A prospective clinical validation, although desirable, would be problematic in the post-vaccine era. In addition, this limitation is substantially mitigated by the objective nature of the predictors, with seizure being the only non-laboratory parameter. The sensitivity for detecting bacterial meningitis is 98%, identical to that observed originally. Given the low likelihood of bacterial meningitis prior to application of the rule, a patient with none of the predictors should have well less than a 1% probability of a positive CSF culture. Clinicians may be advised to be judicious in applying
99
this rule to very young infants. In both studies, cases of missed bacterial meningitis were less than one year of age. Although Nigrovic, et al found a peripheral ANC ⱖ 103 to be an independent predictor of bacterial source, a study of febrile infants less than 90 days old found an inverse relationship between peripheral WBC count and likelihood of bacterial meningitis, suggesting that young infants’ physiological responses to CNS infection may differ.3 Peter C. Wyer, MD Columbia University College of Physicians and Surgeons New York, New York
REFERENCES 1. Attia J, Hatala R, Cook DJ, Wong JG. Does this adult patient have acute meningitis? JAMA. 1999;282(2):175-181. 2. Nigrovic LE, Kupperman N, Malley R. Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-haemophilus influenzae era. Pediatrics. 2002;110:712-719. 3. Bonsu BK, Harper MB. Utility of the peripheral blood count for identifying sick young infants who need lumbar puncture. Ann Emerg Med. 2003;41:206-214.
School-based influenza vaccination program reduces influenza-related outcomes among household members King JC, Stoddard JJ, Gaglani MJ, Moore KA, Magder L, McClure E, et al. Effectiveness of school-based influenza vaccination. N Engl J Med 2006:355:2523-32. Question How effective is a school-based influenza vaccination program at decreasing the incidence of influenza-like illness?
Prospective study of households of elementary school students.
Design
Demographically similar clusters of elementary schools in four states.
Setting
Participants 11 clusters of schools. Intervention schools were assigned to participate in a vaccination program. 1-2 control schools were selected for each cluster. Intervention During a predicted week of peak influenza activity in each state, all households with children in intervention and control schools were surveyed.
Influenza vaccination rates and outcomes of influenza-like illness during the previous 7 days.
Outcomes
Main Results In all, 47% of students in intervention schools received live attenuated influenza vaccine (LAIV). As compared with control-school households, intervention-school households reported significantly fewer influenza-like symptoms and office visits during the recall week; rates of emergency department use did not vary between the two groups. Paradoxically, intervention-school households (both children and adults) had higher rates of hospitalization per 100 persons than did control-school households. However, there was no difference in the overall hospitalization rates for children or adults in households with vaccinated children, as compared with those with unvaccinated
100
children, regardless of study-group assignment. Rates of school absenteeism for any cause (based on school records) were not significantly different between intervention and control schools. Conclusions Most outcomes related to influenza-like illness were significantly lower in intervention school households than in control-school households.
Influenza vaccination rates among children have historically been low,1 especially among children with highrisk conditions.2,3 King, et al illustrate the potential of a population-based program to reduce the burden of influenza-like illness among elementary school children; they do so through an influenza vaccination intervention focused solely on healthy children. Although the findings presented are encouraging, there are several important aspects to bear in mind while interpreting these results. This intervention was restricted to administration of FluMist (MedImmune) live attenuated influenza vaccine (LAIV). Since children with underlying medical conditions such as a chronic disease are not eligible for LAIV, they were excluded from receiving influenza vaccine through the intervention.4 Additionally, this study did not assess the reasons why children chose not to be vaccinated through the school-based program, nor does it control for the degree to which students may have been vaccinated in other settings. These aspects of the study design confound interpretation of the findings presented, such as increased absenteeism among unvaccinated students – a group that presumably includes the entirety of the student population with underlying medical conditions. As a consequence, one cannot determine which characteristics of schools prior to the intervention were associated with the greatest incremental improvements in influenza-related outcomes. In addition, the influenza-like illness outcomes assessed by King et al are based on self-reported data from households, the accuracy of which may be questionable. While the analysis presented does provide an understanding of the overall effect of a school-based LAIV program, it falls short of illustrating the full potential that might be realized by a more comprehensive school-based effort that also includes the option of trivalent inactivated influenza vaccine (TIV). This is an important consideration given the prevalence of chronic conditions among children and the relative expense of LAIV, which is not covered by many insurance programs. Commentary
Kevin Dombkowski, DrPH, MS University of Michigan Ann Arbor, Michigan
REFERENCES 1. Centers for Disease Control and Prevention. Estimated influenza vaccination coverage among adults and children -- United States, September, 1 2004 - January 31, 2005. MMWR Morb Mortal Wkly Rep. 2005;54:304-7. 2. Daley MF, Beaty BL, Barrow J, et al. Missed opportunities for influenza vaccination in children with chronic medical conditions. Arch Pediatr Adolesc Med. 2005;159:986-91. 3. Dombkowski KJ, Davis MM, Cohn LM, Clark SJ. Effect of missed opportunities on influenza vaccination rates among children with asthma. Arch Pediatr Adolesc Med. 2006;160:966-71. 4. Centers for Disease Control and Prevention. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 2006;55:1-42.
The Journal of Pediatrics • July 2007
Clinical Research Abstracts for Pediatricians EDITOR’S NOTE: Journals reviewed for this issue: Archives of Disease in Childhood, Archives of Pediatrics and Adolescent Medicine, British Medical Journal, Journal of the American Medical Association, Journal of Pediatrics, The Lancet, New England Journal of Medicine, Pediatric Infectious Diseases Journal, and Pediatrics. Gurpreet K. Rana, B.Sc., M.L.I.S, Taubman Medical Library, University of Michigan, contributed to the review and selection of this month’s abstracts. —John G. Frohna, MD, MPH
Bacterial meningitis score accurately predicts which children are at low risk Nigrovic LE, Kuppermann N, Macias CG, Cannavino CR, Moro-Sutherland DM, Schremmer RD, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA 2007;297:52-60. Given the widespread use of pneumococcal conjugate vaccine, does the Bacterial Meningitis Score predict which children are at very low risk of bacterial meningitis?
Question
Context Children with cerebrospinal fluid (CSF) pleocyto-
sis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. Design Multicenter, retrospective cohort study. The authors previously developed a clinical prediction rule, the Bacterial Meningitis Score, based on five predictors: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1,000 cells/L, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/L, and a history of seizure before or at the time of presentation. In the current study, patients lacking any of these predictors are classified as low risk.
20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Setting
All children aged 29 days to 19 years who presented to participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells ⱖ10 cells/L) and who had not received antibiotic treatment before lumbar puncture.
Participants
The sensitivity and negative predictive value of the Bacterial Meningitis Score.
Outcome
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%-
Main Results
Clinical Research Abstracts for Pediatricians
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. Conclusions 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. Commentary Meningitis is the most feared infectious entity among febrile infants and children presenting to emergency departments. Studies of clinical diagnosis have not identified reliable criteria for distinguishing between bacterial and viral etiologies.1 The decline in incidence of bacterial meningitis with the advent of effective vaccines against S. pneumoniae and H. influenzae b has heightened the potential value of such criteria in avoiding unnecessary admissions and treatment. Nigrovic, et al’s validation of their previously derived prediction rule is a welcome adjunct to clinical decision making. Their new retrospective study involves an acceptable simplification of the original rule which required calculation of a point score.2 A prospective clinical validation, although desirable, would be problematic in the post-vaccine era. In addition, this limitation is substantially mitigated by the objective nature of the predictors, with seizure being the only non-laboratory parameter. The sensitivity for detecting bacterial meningitis is 98%, identical to that observed originally. Given the low likelihood of bacterial meningitis prior to application of the rule, a patient with none of the predictors should have well less than a 1% probability of a positive CSF culture. Clinicians may be advised to be judicious in applying
99
this rule to very young infants. In both studies, cases of missed bacterial meningitis were less than one year of age. Although Nigrovic, et al found a peripheral ANC ⱖ 103 to be an independent predictor of bacterial source, a study of febrile infants less than 90 days old found an inverse relationship between peripheral WBC count and likelihood of bacterial meningitis, suggesting that young infants’ physiological responses to CNS infection may differ.3 Peter C. Wyer, MD Columbia University College of Physicians and Surgeons New York, New York
REFERENCES 1. Attia J, Hatala R, Cook DJ, Wong JG. Does this adult patient have acute meningitis? JAMA. 1999;282(2):175-181. 2. Nigrovic LE, Kupperman N, Malley R. Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-haemophilus influenzae era. Pediatrics. 2002;110:712-719. 3. Bonsu BK, Harper MB. Utility of the peripheral blood count for identifying sick young infants who need lumbar puncture. Ann Emerg Med. 2003;41:206-214.
School-based influenza vaccination program reduces influenza-related outcomes among household members King JC, Stoddard JJ, Gaglani MJ, Moore KA, Magder L, McClure E, et al. Effectiveness of school-based influenza vaccination. N Engl J Med 2006:355:2523-32. Question How effective is a school-based influenza vaccination program at decreasing the incidence of influenza-like illness?
Prospective study of households of elementary school students.
Design
Demographically similar clusters of elementary schools in four states.
Setting
Participants 11 clusters of schools. Intervention schools were assigned to participate in a vaccination program. 1-2 control schools were selected for each cluster. Intervention During a predicted week of peak influenza activity in each state, all households with children in intervention and control schools were surveyed.
Influenza vaccination rates and outcomes of influenza-like illness during the previous 7 days.
Outcomes
Main Results In all, 47% of students in intervention schools received live attenuated influenza vaccine (LAIV). As compared with control-school households, intervention-school households reported significantly fewer influenza-like symptoms and office visits during the recall week; rates of emergency department use did not vary between the two groups. Paradoxically, intervention-school households (both children and adults) had higher rates of hospitalization per 100 persons than did control-school households. However, there was no difference in the overall hospitalization rates for children or adults in households with vaccinated children, as compared with those with unvaccinated
100
children, regardless of study-group assignment. Rates of school absenteeism for any cause (based on school records) were not significantly different between intervention and control schools. Conclusions Most outcomes related to influenza-like illness were significantly lower in intervention school households than in control-school households.
Influenza vaccination rates among children have historically been low,1 especially among children with highrisk conditions.2,3 King, et al illustrate the potential of a population-based program to reduce the burden of influenza-like illness among elementary school children; they do so through an influenza vaccination intervention focused solely on healthy children. Although the findings presented are encouraging, there are several important aspects to bear in mind while interpreting these results. This intervention was restricted to administration of FluMist (MedImmune) live attenuated influenza vaccine (LAIV). Since children with underlying medical conditions such as a chronic disease are not eligible for LAIV, they were excluded from receiving influenza vaccine through the intervention.4 Additionally, this study did not assess the reasons why children chose not to be vaccinated through the school-based program, nor does it control for the degree to which students may have been vaccinated in other settings. These aspects of the study design confound interpretation of the findings presented, such as increased absenteeism among unvaccinated students – a group that presumably includes the entirety of the student population with underlying medical conditions. As a consequence, one cannot determine which characteristics of schools prior to the intervention were associated with the greatest incremental improvements in influenza-related outcomes. In addition, the influenza-like illness outcomes assessed by King et al are based on self-reported data from households, the accuracy of which may be questionable. While the analysis presented does provide an understanding of the overall effect of a school-based LAIV program, it falls short of illustrating the full potential that might be realized by a more comprehensive school-based effort that also includes the option of trivalent inactivated influenza vaccine (TIV). This is an important consideration given the prevalence of chronic conditions among children and the relative expense of LAIV, which is not covered by many insurance programs. Commentary
Kevin Dombkowski, DrPH, MS University of Michigan Ann Arbor, Michigan
REFERENCES 1. Centers for Disease Control and Prevention. Estimated influenza vaccination coverage among adults and children -- United States, September, 1 2004 - January 31, 2005. MMWR Morb Mortal Wkly Rep. 2005;54:304-7. 2. Daley MF, Beaty BL, Barrow J, et al. Missed opportunities for influenza vaccination in children with chronic medical conditions. Arch Pediatr Adolesc Med. 2005;159:986-91. 3. Dombkowski KJ, Davis MM, Cohn LM, Clark SJ. Effect of missed opportunities on influenza vaccination rates among children with asthma. Arch Pediatr Adolesc Med. 2006;160:966-71. 4. Centers for Disease Control and Prevention. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 2006;55:1-42.
The Journal of Pediatrics • July 2007