RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / Name of the candidate and address ( in block letters) / : / Dr.prashantakumar B Jaikar
DEPARTMENT OF medicine
MAHADEVAPPA RAMPURE MEDICAL COLLEGE, GULBARGA – 585105
Permanent address / : / Dr.prashantakumar B Jaikar
S/O Basavantappa B Jaikar
At Post Hamsabhavi,
TQ: Hirekeror Dist: Haveri -581109
State Karnataka
2 / Name of the institution / : / H.K.E. SOCIETY’S MAHADEVAPPA
RAMPURE MEDICAL COLLEGE,
GULBARGA – 585105
3 / Course of study and subject / : / M.D (General Medicine)
4 / Date of admission to the course / : / 02 June 2011
5 / Title of Topic / : / Levels of serum c-reactive protein estimation in acute meningitis in adults in basaveshwar teaching and general hospital Gulbarga
6 / Brief Resume of the intended work
6.1 / Need for the study
The evolution of clinical signs and symptoms produced by meningitis or encephalitis varies greatly. Few conditions in medicine require as rapid and accurate therapeutic intervention as acute pyogenic meningitis and viral meningitis, yet meningitis can also occur in chronic and recurrent forms. The major problem presented by patients with meningitis is rapid determination of its aetiology, the specific basis on which selection of potentially effective antimicrobial therapy is predicted. Thus, the clinician must sort out the form of clinical presentation, assess the rapidity of its evolution, and make a specific
aetiological diagnosis.
The examination of cerebrospinal fluid is an essential and often critical tool in the evaluation and management of patients with meningitis. If interpreted carefully, the cerebrospinal fluid (CSF) analysis, can be very helpful in guiding the diagnostic evaluation and management of patients. Although examination of a Gram’s stain of spinal fluid often defines the causative agent, this is not always the case. Cultures have the draw back of the time required, 24 to 48 hours or more to become positive, an unacceptable delay in initiating the treatment.
Deivanayagam. N et al (1993)21 Clinical Epidemiology Unit, Madras Medical College, have declared that in developing countries, differentiating bacterial meningitis from viral meningitis and tuberculous meningitis is not easy.
Not all medical centers have viral diagnostic laboratories at their disposal. Moreover, serological confirmation of a viral infection is usually of academic interest, since by the time its result is available, the patients would have recovered or otherwise, it never determines specific therapy.
Further, the cost of antiviral therapy is very high when compared to antimicrobial therapy. So, in developing countries like India, we can not institute empirical antiviral therapy to all patients of suspected viral meningitis. Therefore, several different techniques to discriminate rapidly between viral meningitis and bacterial meningitis have been evaluated. These include Counter Immuno Electrophoresis (CIE) of the CSF for the immunoglobulins, lactic acid, creatine phosphokinase isoenzyme and C-reactive protein. Brown et al (1978)15. Because of easy availability of the kit and simplicity of the procedure, serum C-reactive protein (CRP) was selected to differentiate viral meningitis and bacterial meningitis.
6.2 / Review of Literature.
Gorge pompidu, Rue leblanc in the year 2009 showed that Markers like CRP, procalcitonin, or sTREM-1 may be very useful for the diagnosis and to differentiate between viral and bacterial meningitis. Bacterial meningitis diagnosis and management require various biological tests and a multidisciplinary approach.1
Sirijaichingkul S, Tiamkao S et al in the year 20005 studied serum C-reactive proteins in patients who were diagnosed clinically as bacterial and aseptic meningitis. The study included 32 subjects,12 with bacterial meningitis(all males) and 20 with aseptic meningitis(13males,7females).the mean serum CRP levels in the bacterial meningitis and aseptic meningitis was 209.25+/-105.34(range 65to420)and67.05+/-40.81(range 10to169)mg/dl respectively. They concluded serum CRP can help to differentiate between bacterial and aseptic meningitis.2
Marmelka B ,Lobos M et al in the year 2004 concluded acute phase proteins in serum and cerebrospinal fluid in children with meningitis like concentration of CRP,Alpha1-antitrypsin,alpha1-acid glycoprotein,alpha2-hephatoglobulin and c3 complement fragments were determined in serum and CSFat entryand at 14day . in this study they confirmed serum CRP,Alpha1-antitrypsin,alpha1-acidglycoprotein, alpha2-hepatoglobulin and c3 complement in serum and CSF have diagnostic power that is strong enough to meningitis diagnostic and monitoring power.3
Azeem sheik et all in the year 2001 in their study shown that c-reactive protein was found to be more sensitive test for differentiating bacterial from non-bacterial meningitis on initial examination than usual conventional methods.4
Tankiwale SS, Jagtap PM et al in the year 2001; 75 clinically, biochemically and microscopically diagnosed cases of pyogenic meningitis including 28 adults and 47 children patients were studied gram positive isolates in adults and gram negative bacilli in pediatric age group were predominant organism .estimation c-reactive protein in cerebrospinal fluid and serum was done in all cases an early marker for rapid diagnosis of pyogenic meningitis simultaneous estimation CRP in serum and CSF was found have significant diagnostic utility as compared to culture.5
Tatara R, Imai H.et al in the year 2000 Oct studied Although determination of serum C-reactive protein (CRP) is considered one of the most useful tests for differentiating between bacterial and aseptic meningitis, its diagnostic accuracy in comparison with other laboratory parameters is yet to be further evaluated. A total of 192 pediatric cases, aged between 2 months and 14 years, comprising patients with bacterial meningitis (n = 66) and aseptic meningitis (n = 126), were retrospectively analyzed on the basis of data from the initial examination. The area under the best fit binormal curve of the receiver operating characteristics (Az) for CRP was determined and compared with that for several other analytic parameters, including white blood cell count and erythrocyte sedimentation rate of peripheral blood, standard cerebrospinal fluid analysis variables and the combination test (probability of acute bacterial meningitis (pABM)) derived from Hoen's model. Compared with each of the other variables, the Az for serum CRP (0.97 +/- 0.02) was found to be significantly greater (P < 0.01) for all except pABM (0.99 +/- 0.01; P > 0.05). False-negative cases among the CRP test results were found to have been examined too early they have concluded that The diagnostic accuracy of a single CRP determination was found to be equivalent to that of the most effective combination test. Patients with meningitis in whom serum CRP values are determined at least 12 h after the onset of fever and are < 2 mg/dL are far less likely to have bacterial meningitis.6
Sormunen P, Kallio MJ, et al in the year 1999 Jun studied. To clarify to what extent Gram stain-negative bacterial meningitis can be distinguished from viral meningitis by assessment of cerebrospinal fluid (CSF) and blood indices and serum C-reactive protein (CRP) in children over 3 months of age. Of the tests investigated in this study, only serum CRP was capable of distinguishing Gram stain-negative bacterial meningitis from viral meningitis on admission with high sensitivity (96%), high specificity (93%), and high negative predictive value (99%). Exclusion of bacterial meningitis with only the conventional tests is difficult. Combined with careful physical examination and CSF analyses, serum CRP measurement affords substantial aid.7
Gerdes LU, Jørgensen PE, Nexø E, Wang P in the year 1998 studied. The aim of the study was to review published articles on the diagnostic accuracy of C-reactive protein in meningitis. This, as well as the absence of analyses to show if CRP tests contribute independent diagnostic information, relatively to the information held in the traditionally used clinical and biochemical variable. Makes it helpful to concluded in clinical usefulness of CRP in the management of patient suspected having bacterial meningitis.8
Diculencu D, Miftode E, Turcu T, et al in year 1995 studied that In order to differentiate bacterial meningitis versus viral meningitis, we have comparatively tested the efficacy of the following tests: C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), fever, level of glucose in cerebro-spinal fluid (CSF), glucose in CSF/glycemia ratio, number of white blood cells in peripheric blood, percentage of neutrophils in peripheric blood, level of proteins in CSF and number of nucleated cells in CSF for a group of 49 patients, both children and adults with central nervous system infection (37 patients with bacterial meningitis and 12 with viral meningitis) hospitalized between May 1993 and July 1994 in Clinical Hospital for Infectious Diseases in Iaşi. The mean value of CRP in bacterial meningitis patients was 8.78 mg%, contrasting with the mean value of CRP = 1.92 mg% recorded in patients with viral meningitis. Ten out of 37 bacterial meningitis patients presented a CRP concentration < 1.85 mg%. All these 10 patients have already had an antibiotic treatment at the moment of the assay. One out of 12 cases of viral meningitis had a value of CRP = 3.3 mg%, all the remainder cases having values under 1.85 mg%. We recorded highly significant differences between the two patient groups for CRP (p < 0.001), ESR (p < 0.01), protein concentration in CSF (p < 0.001) and number of nucleated cells in CSF (p < 0.001). Differences recorded for fever, concentration of glucose in CSF, glucose in CSF/glycemia ratio, number of
leucocytes in peripheric blood and percentage of neutrophils in peripheric blood, were not significant (p > 0.5). Data were analysed also by box-plot method which
facilitates the visual appraisal of the differences recorded between the two aetiological groups. In conclusion, assays of CRP and ESR may be used as differentiation tests for bacterial meningitis versus viral meningitis, when assay is done before the antibiotic treatment, being sufficient sensitive, and easy to perfor.9
Paradowski M, Lobos M, et all in year 1995 carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the
areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment10.
Hansson LO, Axelsson G, et al in year 1993An S-CRP value above 50 mg/l in patients with CSF pleocytosis usually indicates bacterial etiology. However, S-CRP values above 50 mg/l may occasionally be seen in viral meningitis can be used to distinguish between bacterial and viral meningitis, but for older patients a discriminatory level of 50 mg/l is more appropriate11.
6.3 / Objectives of the study
1.  To study serum c-reactive protein levels in differentiating bacterial meningitis from viral meningitis
2.  Serum CRP can be sued as best as most sensitive bed side prognostic indicator of bacterial infection.
7 / Materials and Methods
7.1 / Source of data
Patients with definite clinical signs and symptoms of acute meningitis, adged above 12 years admitted in Basaveshwar Teaching and General Hospital, Gulbarga attached to Mahadevappa Rampure Medical College, Gulbarga during November 2011-April 2013.
7.2 / Methods of collection of data ( including sampling procedure, if any)
Inclusion Criteria:
1.  Above 12 years of age
2.  History suggestive of meningitis
3.  Neck rigidity
Exclusion Criteria:
All cases which had the following history were excluded from study in order to avoid false positive S-CRP results.
1.  Recent injury of any kind
2.  Recent surgery
3.  Patient in immediate postpartum period
4.  Known case of Rheumatic heart disease (According to modified Jones criteria)
5.  Known case of Rheumatoid arthritis (According to ARA diagnostic criteria).
6.  Known case of acute or chronic Glomerular nephritis all cases of Genito-urinary tract infection.
7.  Focal infections like pneumonic consolidation infection of skin etc.
8.  Causes for meningism like subarachinoid haemorrage
Setting
This study will be done in-patient setting of Department of internal medicine, Basaveshwara Teaching and General Hospital, Gulbarga.
Study Design
Hospital based (Single center) Cross-sectional study
Period of study: November 2011-April-2013.
Sample size: The study will be done approximately 50 subject admitted in Basaveshwara Teaching and General Hospital, Gulbarga.
Collaborating Department -
.STATICAL ANALSIS; Will be performed SSPSS software pakage and chi –square test . Z-Test, Anova Test and Bar Diagrams will be used for study analysis
7.3 / Does the study require any investigation or intervention to be conducted on patients or other humans or animals? if so please describe briefly
Yes, Study requires following investigations
·  Hb, TC, DC, ESR, Urine routine
·  lECG, 2D Echo, Rheumatoid factor, Serum c-reative protein
·  CSF analysis
·  Chest x-ray PA view
·  Intervention conducted on patients with acute meningitis .
7.4 / Has ethical clearance been obtained from your institution in case of 7.3 ?
Yes, Ethical clearance has been obtained from research and dissertation committee/ethical committee of the institution for this study.
8 / List of References
1.  Georges Pompidou, Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent Med Mal Infect. 2009 Jul-Aug;39(7-8):581-605.
2.  Sirijaichingkul S, Tiamkao S, Sawanyawisuth K, Chotmon. C reactive protein for differentiating bacterial from aseptic meningitis in Thai patients. J Med Assoc Thai. 2005 Sep; 88(9):1251-6.
3.  Mamełka B, Lobos M, Sass-Just M, Dworniak D, Urbaniak A, Terlecka M, Paradowski M. Does the assay of acute phase protein concentrations in cerebrospinal fluid and/or in serum in patient with viral meningitis have a diagnostic value? Part II. Lymphocytic meningitis caused by echo 30 virus]. Przegl Epidemiol. 2004;58(2):351-9.
4.  Azeem Sheik. Department of Medicine. Shaik Zayed hospital, Lahore the diagnostic value of c-reactive protein estimation in differentiating Bacterial from viral meningitis J. Coll Physician Surg. Prak. Oct 2001; 11 (10): 622-4.
5.  Tankhiwale SS ,Jagapat PM, Khadse RK, Bacteriological study of pyogenic meningitis with special reference to CRP. Indira Ghandhi Medical College, Nagapur. Indian Journal of Medical Microbiology 2001vol 19 issue 3pg 159-160.