ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Diagnosis of meningococcal infection

Diagnosis of meningococcal infection
Literature review current through: Jan 2024.
This topic last updated: Oct 12, 2023.

INTRODUCTION — Neisseria meningitidis is the second most common cause of community-acquired adult bacterial meningitis in the United States [1]. Since routine vaccination of infants with the Haemophilus influenzae type b capsular conjugate vaccine was introduced, N. meningitidis has become the leading cause of bacterial meningitis in children and adolescents in the United States. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Causative organisms'.)

The clinical manifestations of meningococcal disease can be quite varied, ranging from transient fever and bacteremia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. (See "Clinical manifestations of meningococcal infection".)

The diagnosis of meningococcal infection will be reviewed here [2-4]. The gold standard for the diagnosis of systemic meningococcal infection is the isolation of N. meningitidis from a usually sterile body fluid, such as blood or cerebrospinal fluid, or, less commonly, synovial, pleural, or pericardial fluid.

The microbiology, pathogenesis, epidemiology, treatment, and prevention of N. meningitidis infection are discussed separately. (See "Microbiology and pathobiology of Neisseria meningitidis" and "Epidemiology of Neisseria meningitidis infection" and "Treatment and prevention of meningococcal infection".)

MICROBIOLOGIC DIAGNOSIS — It is important to isolate the organism not only to confirm an etiology of infection but also to perform antibiotic susceptibility testing. Meningococci with increasing resistance to the penicillins, chloramphenicol, and cephalosporins have been reported [5-10].

Blood culture — The frequency of positive blood cultures is 50 to 60 percent, a much lower rate than the frequency of positive cerebrospinal fluid (CSF) cultures (80 to 90 percent), even in patients without overt meningeal signs [11-16].

Cerebrospinal fluid — The first step in the evaluation of the CSF in a patient with suspected bacterial meningitis is a Gram stain. Gram stain is valuable, even in partially treated meningitis [17]. Bacterial counts in the CSF from patients with meningococcal meningitis have ranged from 1.5 x 102 to 6 x 107 organisms (mean 1.3 x 105) [18].

Chemistry and cytologic findings suggestive of bacterial meningitis include a CSF glucose concentration below 45 mg/dL (2.5 mmol/L), a CSF:serum glucose ratio of <0.4, a protein concentration above 500 mg/dL, and a white cell count above 1000/microL. However, one or more of the classic findings is often absent. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Cerebrospinal fluid analysis'.)

Antibiotic therapy should not be delayed waiting for completion of the lumbar puncture. Blood cultures should be drawn, and plans to institute antibiotic and supportive therapy should begin as soon as the diagnosis of bacterial meningitis is seriously considered [19]. (See "Treatment and prevention of meningococcal infection", section on 'Treatment of meningitis and sepsis' and "Clinical features and diagnosis of acute bacterial meningitis in adults".)

Pretreatment with antibiotics can substantially diminish the probability of a positive CSF culture [20-22], and the time interval between antibiotic administration and negative CSF cultures in children with meningococcal meningitis may be shorter than appreciated. This was illustrated in a study in which lumbar puncture (LP) was performed after antibiotics were given or serial LPs were performed [21]. Among children with meningococcal meningitis who were treated with a parenteral dose of an extended-spectrum cephalosporin, three of nine LPs were sterile within one hour (one as early as 15 minutes), and all were sterile by two hours. Sterilization of the CSF was substantially slower with pneumococcal (4 to 10 hours) and group B streptococcal infection (more than 8 hours).

In contrast with the rapid clearance of meningococcus from the CSF, a small study that assessed the utility of Gram stain and culture from skin biopsies found no correlation between the yield of skin biopsies and previous antibiotic treatment, suggesting slower clearance than from the CSF [23].

Skin biopsy — Skin biopsy may play a role in the diagnosis of meningococcal infection. As an example, Gram stain and culture of a skin lesion can increase the diagnostic yield, although negative results do not exclude the diagnosis of meningococcal infection. In a prospective study evaluating the use of Gram stain and culture from biopsies of skin lesions in 31 patients with suspected meningococcal infection and 12 controls, the sensitivity of cultures of blood, CSF, and skin biopsies was 56, 50, and 36 percent, respectively [23]. When culture and Gram stain were combined, the sensitivity was 56, 64, and 56 percent, respectively. In three patients, the diagnosis of meningococcal infection was based solely upon positive skin biopsy results.

PCR testing of skin biopsy specimens may also have a role in the diagnosis of meningococcal infection. In one report, skin biopsies were shown to be positive in 50 of 51 patients with purpura fulminans [24]. (See "Clinical manifestations of meningococcal infection", section on 'Rash'.)

CEREBROSPINAL FLUID ASSAYS

Antigen detection — Commercial kits utilizing latex beads coated with antibodies to meningococcal capsular antigens are available for use in body fluids other than blood (eg, cerebrospinal fluid [CSF] and urine) [25,26]. These kits can detect agglutination of five capsular types: A, B, C, Y, and W135. The sensitivity for serogroup B is low, and false-negative results can occur [27]. This potential deficiency of the test is especially important because serogroup B has been common in infections in the United States and western Europe. False-positive results have also been reported [28].

Latex agglutination tests are not routinely recommended because of the limitations described above and because results do not appear to modify the decision to administer antimicrobial therapy [29]. However, other rapid diagnostic tests are being developed [30-32]. As an example, a validation study showed a high sensitivity and negative predictive value for an immunochromatographic rapid detection test for identification of meningococcal antigens, which might be useful in low-income countries in the meningitis belt with few laboratory facilities [30,31], but more data are needed.

Polymerase chain reaction — The polymerase chain reaction (PCR), which detects small quantities of bacterial DNA, is an important tool in the rapid diagnosis of meningococcal infection. PCR has a number of advantages compared with culture for the diagnosis of meningococcal infection [22,33-40]:

It can establish the diagnosis more rapidly when available as an in-hospital test. PCR results are often available on the day of presentation compared with one or two days or more for culture confirmation [22].

Since viable bacteria are not required, sensitivity is not affected by prior antibiotic administration, which can sterilize the CSF within one to two hours [21].

It can rapidly type strains, a useful adjunct in situations that appear to be an epidemic in evolution [39,40].

Multiplex PCR permits simultaneous testing for meningococcal, pneumococcal, and H. influenzae infection [41].

The performance of real-time PCR was assessed in a report of 24 patients with meningococcal infection [22]. The sensitivity and specificity were 96 and 100 percent; in contrast, the sensitivity of CSF or blood culture was only 63 percent. In all nine patients in whom blood was tested more than once, PCR remained positive longer than culture after the initiation of antibiotic therapy; in three patients, more than 72 hours longer.

Bacterial load of N. meningitidis DNA level by real-time PCR has been associated with mortality, development of permanent sequelae (eg, limb loss, skin grafting), and prolonged hospitalization [42]. Infections caused by serogroup C were associated with a higher bacterial load and an increased risk of death.

The TaqMan array card is a rapid diagnostic real-time PCR assay that allows simultaneous detection of many viral, bacterial, and parasitic pathogens in blood or CSF [43,44]. It has been used to rapidly identify patients infected with meningococcus in an outbreak in Liberia [45].

Despite these benefits, PCR has not replaced traditional culture methods because it cannot be used to determine antimicrobial susceptibility and is not routinely performed by many hospital laboratories. Another limitation is that false-negative results can occur with N. meningitidis isolates that possess gene polymorphisms, particularly when a single gene is targeted [46,47].

Loop-mediated isothermal amplification — Loop-mediated isothermal amplification (LAMP) is a rapid assay for diagnosis of meningococcal infection in high-risk patients [48,49] and is highly accurate when compared to quantitative PCR and culture. The test is relatively simple to perform in an emergency room setting; the median time from sample collection to result is approximately 90 minutes [48,49].

Studies have shown that LAMP can detect fewer copies of DNA than standard PCR studies [50]. A systematic review that included three studies evaluating 2243 tests on 1989 children using CSF, blood, or naso/oropharyngeal swabs found that LAMP testing is highly accurate (sensitivity 84 to 100 percent and specificity 94 to 100 percent) when compared with quantitative PCR or culture [51].

LAMP systems that can discriminate different meningococcal capsular serogroups have also been developed [52].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in adults" and "Society guideline links: Meningococcal infection" and "Society guideline links: Bacterial meningitis in infants and children".)

SUMMARY AND RECOMMENDATIONS

The gold standard for the diagnosis of systemic meningococcal infection is the isolation of Neisseria meningitidis by culture from a usually sterile body fluid, such as blood or cerebrospinal fluid (CSF), or, less commonly, synovial, pleural, or pericardial fluid. (See 'Introduction' above.)

Isolation of the organism by culture confirms an etiology of infection and permits antibiotic susceptibility testing. (See 'Blood culture' above.)

Gram stain and culture of a skin lesion can increase the diagnostic yield, although a negative result does not exclude the diagnosis. (See 'Skin biopsy' above.)

Antibiotic therapy should not be delayed waiting for performance of lumbar puncture. Blood cultures should be drawn, and plans to institute antibiotic and supportive therapy should begin as soon as the diagnosis of bacterial meningitis is seriously considered. (See 'Cerebrospinal fluid' above.)

Chemistry and cytologic findings suggestive of bacterial meningitis include a CSF glucose concentration below 45 mg/dL (2.5 mmol/L), a CSF:serum glucose ratio <0.4, a protein concentration above 500 mg/dL, and a white cell count above 1000/microL. However, one or more of the classic findings is often absent. (See 'Cerebrospinal fluid' above.)

Commercial latex agglutination kits, which utilize latex beads coated with antibodies to meningococcal capsular antigens, are available for use in body fluids such as CSF and urine. These kits can detect agglutination of five capsular types: A, B, C, Y, and W135, but the sensitivity for serogroup B is low. Other rapid antigen detection tests are being investigated. (See 'Antigen detection' above.)

The polymerase chain reaction (PCR) is a sensitive and rapid tool for diagnosing meningococcal infection. However, PCR has not replaced traditional culture methods because it cannot be used to determine antimicrobial susceptibility and is not routinely performed by most hospital laboratories. (See 'Polymerase chain reaction' above.)

  1. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med 2011; 364:2016.
  2. Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J Med 2001; 344:1378.
  3. Gardner P. Clinical practice. Prevention of meningococcal disease. N Engl J Med 2006; 355:1466.
  4. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 2007; 369:2196.
  5. Angyo IA, Okpeh ES. Changing patterns of antibiotic sensitivity and resistance during an outbreak of meningococcal infection in Jos, Nigeria. J Trop Pediatr 1998; 44:263.
  6. Galimand M, Gerbaud G, Guibourdenche M, et al. High-level chloramphenicol resistance in Neisseria meningitidis. N Engl J Med 1998; 339:868.
  7. Sprott MS, Kearns AM, Field JM. Penicillin-insensitive Neisseria meningitidis. Lancet 1988; 1:1167.
  8. Mendelman PM, Campos J, Chaffin DO, et al. Relative penicillin G resistance in Neisseria meningitidis and reduced affinity of penicillin-binding protein 3. Antimicrob Agents Chemother 1988; 32:706.
  9. Sáez-Nieto JA, Lujan R, Berrón S, et al. Epidemiology and molecular basis of penicillin-resistant Neisseria meningitidis in Spain: a 5-year history (1985-1989). Clin Infect Dis 1992; 14:394.
  10. Fangio P, Desbouchages L, Lachérade JC, et al. Neisseria meningitidis C:2b:P1.2,5 with decreased susceptibility to penicillin isolated from a patient with meningitis and purpura fulminans. Eur J Clin Microbiol Infect Dis 2005; 24:140.
  11. HOYNE AL, BROWN RH. Seven hundred and twenty seven meningococcic cases; an analysis. Ann Intern Med 1948; 28:248.
  12. TOBIN JL. Complications of meningococcus infection in a series of sixty-three consecutive sporadic cases. Am J Med Sci 1956; 231:241.
  13. McCracken GH Jr. Rapid identification of specific etiology in meningitis. J Pediatr 1976; 88:706.
  14. CARPENTER RR, PETERSDORF RG. The clinical spectrum of bacterial meningitis. Am J Med 1962; 33:262.
  15. Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993; 328:21.
  16. Levin S, Painter MB. The treatment of acute meningococcal infection in adults. A reappraisal. Ann Intern Med 1966; 64:1049.
  17. Finlay FO, Witherow H, Rudd PT. Latex agglutination testing in bacterial meningitis. Arch Dis Child 1995; 73:160.
  18. Feldman WE. Relation of concentrations of bacteria and bacterial antigen in cerebrospinal fluid to prognosis in patients with bacterial meningitis. N Engl J Med 1977; 296:433.
  19. Tunkel AR, van de Beek D, Scheld WM. Acute meningitis. In: Principles and Practice of Infectious Diseases, 7th ed, Mandell GL, Bennett JE, Dolin R (Eds), Churchill Livingstone, Philadelphia 2010. p.1189.
  20. Bohr V, Rasmussen N, Hansen B, et al. 875 cases of bacterial meningitis: diagnostic procedures and the impact of preadmission antibiotic therapy. Part III of a three-part series. J Infect 1983; 7:193.
  21. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001; 108:1169.
  22. Bryant PA, Li HY, Zaia A, et al. Prospective study of a real-time PCR that is highly sensitive, specific, and clinically useful for diagnosis of meningococcal disease in children. J Clin Microbiol 2004; 42:2919.
  23. Arend SM, Lavrijsen AP, Kuijken I, et al. Prospective controlled study of the diagnostic value of skin biopsy in patients with presumed meningococcal disease. Eur J Clin Microbiol Infect Dis 2006; 25:643.
  24. Contou D, Béduneau G, Rabault C, et al. Skin biopsy in adult patients with meningococcal purpura fulminans: a multicenter retrospective cohort study. Crit Care 2023; 27:166.
  25. Muller PD, Donald PR, Burger PJ, van der Horst W. Detection of bacterial antigens in cerebrospinal fluid by a latex agglutination test in 'septic unknown' meningitis and serogroup B meningococcal meningitis. S Afr Med J 1989; 76:214.
  26. Borel T, Rose AM, Guillerm M, et al. High sensitivity and specificity of the Pastorex latex agglutination test for Neisseria meningitidis serogroup A during a clinical trial in Niger. Trans R Soc Trop Med Hyg 2006; 100:964.
  27. McGraw TP, Bruckner DA. Evaluation of the Directigen and Phadebact agglutination tests. Am J Clin Pathol 1984; 82:97.
  28. Hayden RT, Frenkel LD. More laboratory testing: greater cost but not necessarily better. Pediatr Infect Dis J 2000; 19:290.
  29. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
  30. van de Beek D, Brouwer MC, Koedel U, Wall EC. Community-acquired bacterial meningitis. Lancet 2021; 398:1171.
  31. Haddar CH, Terrade A, Verhoeven P, et al. Validation of a New Rapid Detection Test for Detection of Neisseria meningitidis A/C/W/X/Y Antigens in Cerebrospinal Fluid. J Clin Microbiol 2020; 58.
  32. Collard JM, Wang X, Mahamane AE, et al. A five-year field assessment of rapid diagnostic tests for meningococcal meningitis in Niger by using the combination of conventional and real-time PCR assays as a gold standard. Trans R Soc Trop Med Hyg 2014; 108:6.
  33. Ni H, Knight AI, Cartwright K, et al. Polymerase chain reaction for diagnosis of meningococcal meningitis. Lancet 1992; 340:1432.
  34. Newcombe J, Cartwright K, Palmer WH, McFadden J. PCR of peripheral blood for diagnosis of meningococcal disease. J Clin Microbiol 1996; 34:1637.
  35. Borrow R, Claus H, Chaudhry U, et al. siaD PCR ELISA for confirmation and identification of serogroup Y and W135 meningococcal infections. FEMS Microbiol Lett 1998; 159:209.
  36. Speers DJ, Jelfs J. Typing of Neisseria meningitidis by restriction analysis of the amplified porA gene. Pathology 1997; 29:201.
  37. Newcombe J, Dyer S, Blackman L, et al. PCR-single-stranded confirmational polymorphism analysis for non-culture-based subtyping of meningococcal strains in clinical specimens. J Clin Microbiol 1997; 35:1809.
  38. Diggle MA, Clarke SC. Detection and genotyping of meningococci using a nested PCR approach. J Med Microbiol 2003; 52:51.
  39. Diggle MA, Clarke SC. Molecular methods for the detection and characterization of Neisseria meningitidis. Expert Rev Mol Diagn 2006; 6:79.
  40. Meningococcal Reference Unit, Gray SJ, Trotter CL, et al. Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the Meningococcal Reference Unit. J Med Microbiol 2006; 55:887.
  41. Corless CE, Guiver M, Borrow R, et al. Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 2001; 39:1553.
  42. Darton T, Guiver M, Naylor S, et al. Severity of meningococcal disease associated with genomic bacterial load. Clin Infect Dis 2009; 48:587.
  43. Onyango CO, Loparev V, Lidechi S, et al. Evaluation of a TaqMan Array Card for Detection of Central Nervous System Infections. J Clin Microbiol 2017; 55:2035.
  44. Kodani M, Yang G, Conklin LM, et al. Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens. J Clin Microbiol 2011; 49:2175.
  45. Patel JC, George J, Vuong J, et al. Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017. MMWR Morb Mortal Wkly Rep 2017; 66:1144.
  46. Cavrini F, Liguori G, Andreoli A, Sambri V. Multiple nucleotide substitutions in the Neisseria meningitidis serogroup C ctrA gene cause false-negative detection by real-time PCR. J Clin Microbiol 2010; 48:3016.
  47. Jaton K, Ninet B, Bille J, Greub G. False-negative PCR result due to gene polymorphism: the example of Neisseria meningitidis. J Clin Microbiol 2010; 48:4590.
  48. Bourke TW, Fairley DJ, McKenna JP, et al. Clinical Evaluation of Streptococcus pneumoniae Polymerase Chain Reaction in Children with Suspected Septicemia. Pediatr Infect Dis J 2015; 34:1276.
  49. Notomi T, Okayama H, Masubuchi H, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res 2000; 28:E63.
  50. Lee D, Kim EJ, Kilgore PE, et al. Clinical evaluation of a loop-mediated isothermal amplification (LAMP) assay for rapid detection of Neisseria meningitidis in cerebrospinal fluid. PLoS One 2015; 10:e0122922.
  51. Waterfield T, Fairley D, Blackwood B, et al. A systematic review of the diagnostic accuracy of Loop-mediated-isothermal AMPlification (LAMP) in the diagnosis of invasive meningococcal disease in children. BMC Pediatr 2019; 19:49.
  52. Lee D, Kim EJ, Kilgore PE, et al. A Novel Loop-Mediated Isothermal Amplification Assay for Serogroup Identification of Neisseria meningitidis in Cerebrospinal Fluid. Front Microbiol 2015; 6:1548.
Topic 1281 Version 24.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟