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Diagnosis of bacterial meningitis
CORRESPONDENCE
Diagnosis of bacterial meningitis Sir—James Berkley and colleagues (June 2, p 1753)1 make an important observation on the inadequacy of current diagnostic tools for bacterial meningitis typical of less-developed countries. In designing their study, however, they have not given consideration to present clinical and laboratory practice in most of such countries. The usefulness of neck stiffness is overstated, especially in young children.2 Thus, most physicians would include in their work-up a lumbar puncture for children younger than 1 year who seem clinically septic, irrespective of stiff neck. Turbidity of cerebrospinal fluid is a subjective description, and a correlation of this description with cell count would have been helpful. In practice, the physician who does a lumbar tap assesses the fluid macroscopically and starts antibiotic treatment on the basis of the physical appearance of the sample and clinical data. Management is modified if necessary after laboratory tests. Berkley and colleagues’ analysis of the description made by the attending physician of the cerebrospinal fluid would have been relevant, as would that made by the laboratory technician. Berkley and colleagues allude to previous antibiotic use being uncommon in their community, but 25% of their samples were visibly turbid without bacterial isolate. Formal screening of these patients for previous antimicrobial use would have been invaluable. Further information could also have been obtained from latex agglutination screening, which is more specific, less labour-intensive, and cheaper than glucose measurement. The diagnostic potential of gram stain microscopy might have also been underestimated, since this test is diagnostic in up to 90% of bacterial meningitis cases in some series.3 The laboratory assessment of the cerebrospinal fluid cells was not very descriptive. Samples that were visibly red were not analysed for cell count, but Berkley and colleagues give no correction factor for the number of red blood cells in interpreting the number of white blood cells. In some facilities, clinical and management decisions are made on the cell type and the number. Thus, patients with cerebrospinal fluid pleocytosis lower than the arbitrary cutoff of 50⫻106/mL might, on further assessment, have had a preponderance of polymorphonuclear cells that would prompt a diagnosis of bacterial meningitis.
THE LANCET • Vol 358 • November 3, 2001
Berkley and colleagues use for their blood cultures the BACTEC system, which is a new bacterial culture system available in less-developed countries. This system has time-to-detection advantages, but it has not yet been formally compared with standard culture techniques available to most health facilities in such countries. Therefore, culture results might have been overly sensitive. The researchers excluded cultures of presumed contaminants from analysis, but did not note what proportion of their cultures were contaminated. Berkeley and colleagues have highlighted a gap in the understanding of the burden of bacterial meningitis and, by implication, several other lifethreatening infectious diseases in lessdeveloped countries, many of which are potentially preventable through vaccination. Although improvement in diagnosis is urgently required, the emphasis should be on identification of causes so that appropriate interventions can be applied. G E Enwere, *S K Obaro Medical Research Council Laboratories, Fajara, PO Box 273, Banjul, The Gambia 1
2
3
Berkley JA, Mwangi I, Ngesta CJ, et al. Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa. Lancet 2001; 357: 1753–57. Radestky M. Duration of symptoms and outcomes in bacterial meningitis: an analysis of causation and the implications of a delay in diagnosis. Pediatr Infect Dis J 1992; 11: 694–98. Arditi M, Mason EO Jr, Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characterisitcs and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998; 102: 1087–97.
Authors’ reply Sir—Our findings support the view that clinical signs, such as neck stiffness, have a low sensitivity. This increases reliance on lumbar puncture and the ability to analyse cerebrospinal fluid. Culture of cerebrospinal fluid is not available in most African district hospitals, and other tests are frequently unavailable or unreliable. We are especially concerned about the common practice of starting antibiotic treatment on the basis of naked-eye CSF turbidity
– (n=802) + (n=33) ++ (n=15) +++ (n=8) Blood-stained (n=47)
assessment of cerebrospinal fluid for turbidity. In our study, 11 (24·4%) of 45 children with microbiologically proven bacterial meningitis did not have turbid cerebrospinal fluid. Even if bloodstained samples were excluded, more than 25% of children with a cerebrospinal fluid leucocyte count of more than 50⫻106/L were not identified (table). Our data suggest that this practice is likely to result in missed or dangerously delayed diagnosis and treatment. We were unable to screen patients for antibiotic use. There is limited formal primary health care in Kilifi, but antibiotics are available from informal sources. We did latex agglutination screening for Streptococcus pneumoniae and Haemophilus influenzae on cerebrospinal fluid samples if white cell count was higher than 10⫻106/L. The cost of latex agglutination screening is around US$1.50 per antigen, which is beyond the means of most African district hospitals. Gram stain was diagnostic in 26 (67%) of 39 proven cases and was not possible in six grossly bloodstained samples from confirmed cases. Enwere and Obaro suggest that a preponderance of cerebrospinal fluid polymorphonuclear cells may be used to distinguish bacterial meningitis from other causes. In our study, 103 children had a cerebrospinal fluid leucocyte count higher than 10⫻106/L. A differential cell count was done in 97 children, of whom 31 had proven bacterial meningitis. Only six had fewer than 50% polymorphonuclear cells, two of which were proven bacterial cases. Of 91 with 50% or more polymorphonuclear cells, 29 (31%) were proven bacterial cases. By use of a more stringent cut-off of 80%, 21 had fewer than 80% polymorphonuclear cells, with seven (33%) proven bacterial cases, and 76 had 80% or more polymorphonuclear cells with 24 (32%) confirmed cases. Thus we would not rely on the differential cell count to exclude a diagnosis of bacterial meningitis in this environment. As regards blood cultures, in an initial comparison between our existing method, inoculation into Brain Heart Infusion Broth, and the BACTEC
CSF leucocytes (⫻106/L) Median (IQR)
>10 (n [%])
>50 (n [%])
2 (0–4) 162 (10–364) 1111 (620–1900) Too numerous Unassessable
64 (8%) 22 (66%) 15 (100%) 8 (100%)* ··
15 (2%) 19 (58%) 15 (100%) 8 (100%)* ··
CSF=cerebrospinal fluid. *Assumed.
Cerebrospinal fluid leucocyte counts in relation to visible turbidity
1549
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Diagnosis of bacterial meningitis Sir—James Berkley and colleagues (June 2, p 1753)1 make an important observation on the inadequacy of current diagnostic tools for bacterial meningitis typical of less-developed countries. In designing their study, however, they have not given consideration to present clinical and laboratory practice in most of such countries. The usefulness of neck stiffness is overstated, especially in young children.2 Thus, most physicians would include in their work-up a lumbar puncture for children younger than 1 year who seem clinically septic, irrespective of stiff neck. Turbidity of cerebrospinal fluid is a subjective description, and a correlation of this description with cell count would have been helpful. In practice, the physician who does a lumbar tap assesses the fluid macroscopically and starts antibiotic treatment on the basis of the physical appearance of the sample and clinical data. Management is modified if necessary after laboratory tests. Berkley and colleagues’ analysis of the description made by the attending physician of the cerebrospinal fluid would have been relevant, as would that made by the laboratory technician. Berkley and colleagues allude to previous antibiotic use being uncommon in their community, but 25% of their samples were visibly turbid without bacterial isolate. Formal screening of these patients for previous antimicrobial use would have been invaluable. Further information could also have been obtained from latex agglutination screening, which is more specific, less labour-intensive, and cheaper than glucose measurement. The diagnostic potential of gram stain microscopy might have also been underestimated, since this test is diagnostic in up to 90% of bacterial meningitis cases in some series.3 The laboratory assessment of the cerebrospinal fluid cells was not very descriptive. Samples that were visibly red were not analysed for cell count, but Berkley and colleagues give no correction factor for the number of red blood cells in interpreting the number of white blood cells. In some facilities, clinical and management decisions are made on the cell type and the number. Thus, patients with cerebrospinal fluid pleocytosis lower than the arbitrary cutoff of 50⫻106/mL might, on further assessment, have had a preponderance of polymorphonuclear cells that would prompt a diagnosis of bacterial meningitis.
THE LANCET • Vol 358 • November 3, 2001
Berkley and colleagues use for their blood cultures the BACTEC system, which is a new bacterial culture system available in less-developed countries. This system has time-to-detection advantages, but it has not yet been formally compared with standard culture techniques available to most health facilities in such countries. Therefore, culture results might have been overly sensitive. The researchers excluded cultures of presumed contaminants from analysis, but did not note what proportion of their cultures were contaminated. Berkeley and colleagues have highlighted a gap in the understanding of the burden of bacterial meningitis and, by implication, several other lifethreatening infectious diseases in lessdeveloped countries, many of which are potentially preventable through vaccination. Although improvement in diagnosis is urgently required, the emphasis should be on identification of causes so that appropriate interventions can be applied. G E Enwere, *S K Obaro Medical Research Council Laboratories, Fajara, PO Box 273, Banjul, The Gambia 1
2
3
Berkley JA, Mwangi I, Ngesta CJ, et al. Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa. Lancet 2001; 357: 1753–57. Radestky M. Duration of symptoms and outcomes in bacterial meningitis: an analysis of causation and the implications of a delay in diagnosis. Pediatr Infect Dis J 1992; 11: 694–98. Arditi M, Mason EO Jr, Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characterisitcs and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998; 102: 1087–97.
Authors’ reply Sir—Our findings support the view that clinical signs, such as neck stiffness, have a low sensitivity. This increases reliance on lumbar puncture and the ability to analyse cerebrospinal fluid. Culture of cerebrospinal fluid is not available in most African district hospitals, and other tests are frequently unavailable or unreliable. We are especially concerned about the common practice of starting antibiotic treatment on the basis of naked-eye CSF turbidity
– (n=802) + (n=33) ++ (n=15) +++ (n=8) Blood-stained (n=47)
assessment of cerebrospinal fluid for turbidity. In our study, 11 (24·4%) of 45 children with microbiologically proven bacterial meningitis did not have turbid cerebrospinal fluid. Even if bloodstained samples were excluded, more than 25% of children with a cerebrospinal fluid leucocyte count of more than 50⫻106/L were not identified (table). Our data suggest that this practice is likely to result in missed or dangerously delayed diagnosis and treatment. We were unable to screen patients for antibiotic use. There is limited formal primary health care in Kilifi, but antibiotics are available from informal sources. We did latex agglutination screening for Streptococcus pneumoniae and Haemophilus influenzae on cerebrospinal fluid samples if white cell count was higher than 10⫻106/L. The cost of latex agglutination screening is around US$1.50 per antigen, which is beyond the means of most African district hospitals. Gram stain was diagnostic in 26 (67%) of 39 proven cases and was not possible in six grossly bloodstained samples from confirmed cases. Enwere and Obaro suggest that a preponderance of cerebrospinal fluid polymorphonuclear cells may be used to distinguish bacterial meningitis from other causes. In our study, 103 children had a cerebrospinal fluid leucocyte count higher than 10⫻106/L. A differential cell count was done in 97 children, of whom 31 had proven bacterial meningitis. Only six had fewer than 50% polymorphonuclear cells, two of which were proven bacterial cases. Of 91 with 50% or more polymorphonuclear cells, 29 (31%) were proven bacterial cases. By use of a more stringent cut-off of 80%, 21 had fewer than 80% polymorphonuclear cells, with seven (33%) proven bacterial cases, and 76 had 80% or more polymorphonuclear cells with 24 (32%) confirmed cases. Thus we would not rely on the differential cell count to exclude a diagnosis of bacterial meningitis in this environment. As regards blood cultures, in an initial comparison between our existing method, inoculation into Brain Heart Infusion Broth, and the BACTEC
CSF leucocytes (⫻106/L) Median (IQR)
>10 (n [%])
>50 (n [%])
2 (0–4) 162 (10–364) 1111 (620–1900) Too numerous Unassessable
64 (8%) 22 (66%) 15 (100%) 8 (100%)* ··
15 (2%) 19 (58%) 15 (100%) 8 (100%)* ··
CSF=cerebrospinal fluid. *Assumed.
Cerebrospinal fluid leucocyte counts in relation to visible turbidity
1549
For personal use. Only reproduce with permission from The Lancet Publishing Group.