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Table of Contents    
COMMENTARY
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 1050-1051

Clinical utility of latex agglutination test for the rapid diagnosis of acute bacterial meningitis


1 Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India
2 Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. Vimal K Paliwal
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow - 226 014, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.237007

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How to cite this article:
Paliwal VK, Tejan N. Clinical utility of latex agglutination test for the rapid diagnosis of acute bacterial meningitis. Neurol India 2018;66:1050-1

How to cite this URL:
Paliwal VK, Tejan N. Clinical utility of latex agglutination test for the rapid diagnosis of acute bacterial meningitis. Neurol India [serial online] 2018 [cited 2018 Aug 17];66:1050-1. Available from: http://www.neurologyindia.com/text.asp?2018/66/4/1050/237007




The search for an effective strategy for the rapid diagnosis of acute bacterial meningitis is ongoing. The challenge lies not only in the timely diagnosis of acute bacterial meningitis, but also in differentiating it from acute viral, fungal and tuberculous meningitis, and in determining the antibiotic sensitivity for an early and effective treatment of bacteremia. The diagnosis of acute bacterial meningitis relies chiefly on the routine biochemical examination, cell count, light microscopy and bacterial culture of the cerebrospinal fluid (CSF) of patients with suspected meningitis. The bacterial load in the CSF is the major determinant of microscopy. It has been reported that the chance of a positive microscopy is only 25% if the bacterial concentration is 103 colony-forming units per milliliter (cfu/ml). If the concentration ranges from 103 to 105 cfu/ml, the chances increase to 60%. CSF culture can be negative in patients who have received prior antibiotics.[1] In the case of N meningitidis, CSF sterilization happens within 2 hours of administration of a third generation cephalosporin.[2] Nevertheless, the bacterial culture is the only gold-standard test that can grow organisms on a culture media, can help in identification of the organism (genus and species), and also help in generating the antibiogram. However, it takes several hours-to-days to grow the organisms. Moreover, despite an adequate incubation, the culture may not grow anything in a large proportion of CSF samples. Therefore, the treating team has to rely on the empirical antibiotics that are decided based on the age of patients, co-morbidities, local epidemiology and the sensitivity patterns as per the local microbiological laboratory reports. Acute bacterial meningitis is a dreaded disease with very high mortality rate. We have all experienced that a delay in the treatment for even a few hours and a wrong choice of antibiotics, early in the course of treatment, can lead to adverse outcomes.

Rapid diagnostic tests are in practice for a very long time. The agglutination tests are basically the precipitation reactions that occur on the cell surface (usually erythrocytes), which are coated with the sensitized gamma globulins. The precipitation (or agglutination) of erythrocytes occurs when they are mixed with the patient's serum that contains the antigen. Due to the antigenic nature of the complex organic structure of the erythrocytes, Singer JM and Plotz CM used latex beads in place of sheep erythrocyte for the first time in 1956 for the agglutination test.[3]

The first test that used the principle of agglutination reaction was done for detecting rheumatoid factor (antigen) in the serum of the patients suffering from rheumatoid arthritis. The first few reports of identification of microorganisms by counter immune electrophoresis and co-agglutination in the blood/CSF came in the late 1970s and early 1980s, respectively. Polymerase chain reaction (PCR) has also been in use for the diagnosis of different bacterial infections since the late 1990s. A number of studies have been done worldwide to determine the epidemiology of acute bacterial meningitis in different geographical regions by using these rapid tests in addition to the conventional methods. Many studies have also tried to determine the sensitivity/specificity of these tests using culture as a gold standard. Have these tests really changed the way we treat acute bacterial meningitis? Have they contributed in devising the approach of preventive strategies at the community level? The study in focus by Chauhan D et al., has forced us to think about the utility of the rapid tests especially the latex agglutination test in the diagnosis of ABM.[4]

The sensitivity of antigen detection kits by the latex agglutination method varies from 50% to 100% in Gram stain or culture positive samples. The reported sensitivity of the CSF bacterial antigen is quite variable in the culture negative samples.[5] The present study reports a very high sensitivity and specificity but these results appear to be too optimistic because of a very low yield from the blood culture in their patients. The results of antigen detection can be influenced by various factors like non-specific reactions due to the presence of hemolysed red blood cells, the presence of rheumatoid factor and a low concentration of antigen in the sample. The latex agglutination test is less sensitive for  Neisseria More Details meningitidis.[1] The kit based latex agglutination tests do not detect meningitis due to pathogens like Listeria monocytogenes, Staphylococcus aureus, Enterobacteriaeceae members other than  Escherichia More Details coli and Mycobacterium tuberculosis. There are also reports of cross-reactivity between different organisms. A positive rapid test provides only a limited help in deciding the empirical antibiotic, especially in the culture negative patients. Despite all these shortcomings, we believe that the kit-based tests are important in the real world. It is always better to have some rationale for initiating empirical antibiotics rather than groping in the dark. The kit-based tests are easily available, easy to standardize, very simple to perform on a routine basis and provide very prompt results. They are also helpful in patients with partially treated pyogenic meningitis. A positive rapid test along with the clinical, biochemical and radiological data are helpful in deciding the effective treatment strategy in a majority of patients. Despite the availability of so many tests, acute bacterial meningitis remains inherently associated with a poor prognosis. Early mortality is usually due to a delay in the initiation of treatment, late arrival of patients at the tertiary care centers, associated septicemia, hypotension and vascular cerebral complications associated with acute bacterial meningitis. One of the strengths of the study by Chauhan D et al.,[4] was a 6- month follow up of their patients that helped in documenting a very high rate of morbidity in these children. The study, therefore, re-emphasizes the fact that there is a need to identify and treat acute bacterial meningitis at the earliest instance that it is detected.

The epidemiological data on children with acute bacterial meningitis is quite variable. The common bacteria associated are Streptococcus pneumoniae, Group B Streptococcus, Hemophilus influenzae, Niesseria meningitidis, Escherichia coli, Staphylococcus aureus and Listeria monocytogenes. Globally, the most prevalent bacterial pathogens isolated from acute meningitis cases are Streptococcus pneumoniae and  Neisseria meningitidis More Details.[6] The prevalence rates differ among different geographical areas. In a large study from India, majority of the cases of bacterial meningitis were found to be due to Streptococcus pneumoniae followed by Hemophilus influenzae and Neisseria meningitidis.[7] In this study by Chauhan D et al.,[4] the maximum prevalence was seen for group B Streptococcus. The authors have not explained the probable reason for this deviation of their data from the usual Indian and global data. In our view, more epidemiological studies from Himachal Pradesh and the adjoining states are required to better understand the prevalence rates of different bacteria in childhood acute bacterial meningitis in their geographical area. This will also help in understanding the other shortcomings of the rapid tests. The data derived prospectively from the rapid tests can also be compared with the retrospectively collected microbiological data derived from the CSF/blood culture reports of patients with acute bacterial meningitis. This can provide a reason to believe in the validity and accuracy of the rapid tests. A periodic news letter from the local microbiological laboratory (especially in the tertiary care centers) showing the current antibiotic sensitivity patterns derived from the blood/CSF culture samples can also help the clinicians to better utilize the rapid tests in deciding the appropriate antibiotics in patients with acute bacterial meningitis.



 
  References Top

1.
Kim KS. Acute bacterial meningitis in infants and children. Lancet Infect Dis 2010;10:32-42.  Back to cited text no. 1
    
2.
Yahia MA, Balach OM. Comparison of multiplex PCR, Gram stain, and culture for diagnosis of acute bacterial meningitis. Int J Pharm Pharm Sci 2014;6:425-9.  Back to cited text no. 2
    
3.
Singer JM, Plotz CM. The latex fixation test. I. Application to the serologic diagnosis of rheumatiod arthritis. Am J Med 1956;21:888-92.  Back to cited text no. 3
    
4.
Chauhan D, Mokta K, Kanga A, Grover N. Epidemiology, clinical profile and role of rapid tests in the diagnosis of acute bacterial meningitis in children (aged 1-59 months). Neurol India 2018;66: 1045-9.   Back to cited text no. 4
  [Full text]  
5.
Tarafdar K, Rao S, Recco RA, Zaman MM. Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the cerebrospinal fluid of patients with culture-negative meningitis. Clin Infect Dis 2001;33:406-8.  Back to cited text no. 5
    
6.
Oordt-Speets AM, Bolijn R, van Hoorn RC, Bhavsar A, Kyaw MH. Global etiology of bacterial meningitis: A systematic review and meta-analysis. PloS one 2018;13:e0198772.  Back to cited text no. 6
    
7.
Jayaraman Y, Veeraraghavan B, Chethrapilly Purushothaman GK, et al. Burden of bacterial meningitis in India: Preliminary data from a hospital based sentinel surveillance network. PLoS one 2018;13:e0197198. doi: 10.1371/journal.pone.0197198.  Back to cited text no. 7
    




 

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