¹Junior Resident, ²Professor and HOD, Department of Paediatrics, Vilasrao Deshmukh Government Institute of Medical Sciences, Latur, Maharashtra, INDIA.

Email: dhanmati25@gmail.com

RESULTS

The study population included 90 patients clinically suspected to have CNS infection in the age group of 1month to 12 years of age, out of which maximum number of patients (44) belonged to 2-5 years age group and least cases (8) in 11-15 years of age group. Male were 51 (56.7%) and females 39 (43.3%) of all cases with M:F ratio of 1.3:1.

Table 1: Age and gender distribution

The presenting features included fever in all 90 cases (100%), altered sensorium in 70(77.8%), seizures in 87(96.7%), posturing in 23(25.6%) and signs of meningitis like irritability, headache, vomiting, neck rigidity in 64(71.1%) cases.

Table 2: Clinical features and history

The aetiological diagnosis with evidence of etiology in CSF could be made in 1 case for viral encephalitis with JE IgM positive, CSF culture showed growth in 12 cases of bacterial meningitis, CSF CBNAAT detected Mycobacterium in 1 case, Gastric lavage CBNAAT in 1 case and CSF Gram staining was positive in total 8 cases and ZN staining for AFB in 2 cases. Otherwise, based on history, clinical features, CSF analysis and other diagnostic tests, diagnosis of viral meningitis/encephalitis was made in 50 cases (55.6%), bacterial in 30 (33.3%), TBM in 8 (8.9%), and Rickettsial and Fungal (Candida albicans) meningitis in 1 (1.1%) case each.

Table 3: Aetiology of CNS infection

The blood culture showed growth in 22 cases of which MRSA was seen in 6(6.7%); Salmonella enteritidis and Streptococcus pyogenes in 3 cases each(3.3%); Non-fermenters and Pseudomonas aeruginosa in 2 cases each(2.2%); Streptococcus pneumoniae, Group B Streptococcus, E. coli, Citrobacter, Acinetobacter and Candida albicans in 1 case each(1.1%). CSF culture showed growth in 12 cases of which Salmonella enteritidis, Pseudomonas aeruginosa, MRSA and Non-fermenters were seen in 2(2.2%) cases each while E. coli, CoNS, Citrobacter, Acinetobacter were seen in 1 case each (1.1%).

Table 4: Blood and Cerebrospinal fluid (CSF) culture of organisms.

Outcome wise, total deaths i.e. case fatality rate (CFR) was 13 (14.4%) and 74 (82.2%) patients were discharged.

Table 5: Outcome

DISCUSSION

There is no standard laboratory diagnostic strategy for investigation of encephalitis and even experienced physicians are often uncertain about the cause, appropriate therapy and prognosis.⁵ Many a times even after an extensive diagnostic workup it may not be possible to identify the specific organism⁶ and hence a detailed examination and workup is needed as many conditions, such as infections are well treatable. However, not all febrile illnesses are due to infections and hence a detailed enquiry of other factors like exposure to drugs, toxins, immunization, exposure to high temperature etc. should be done.⁷ In present study, prevalence of CNS infection was maximum in the age group of 2-5 years (48.9%, 44 cases) which is in accordance with study by S.A Karmarkar et al.⁸ and C.M. Bokade et al. ⁹ where too the mean age group was 3.2±2.9 years. The male to female ratio M:F in present study is 1.3:1 which is comparable to studies by Garg et al.¹⁰, SK Rathore et al.², SA Karmarkar et al.⁸ and Debnath et al. ¹¹ where the M:F ratio is 2:1, 1.6:1, 1.7:1 and 1.8:1 respectively. The lower prevalence in females can be attributed to production of gamma-globulin regulated by certain factors on X chromosome.^10,12 The higher incidence of CNS infections in males compared to females can also be explained by the time spent outdoor by male children and indulging in unhygienic activities resulting in an increased exposure to certain vectors and agents which might increase the risk of infection. It is also influenced by certain social and cultural practices.¹³

The Case fatality rate (CFR) in present study was 13(14.4%) which is comparable to studies by Garg et al. (10.5%)¹⁰, Debnath et al. (13.9%)¹¹ and C.M. Bokade et al.⁹ (19.3%). The mortality was more in cases of TBM (3 cases) and Dengue encephalitis 3 cases (3.3% each). The comparatively higher mortality in TBM could be attributed to late presentation, delay in diagnosis, poor nutrition and complications in these cases like hydrocephalus and cerebral infarcts evident on MRI of these cases.¹⁴ Similarly, cases of Dengue encephalitis had complications like refractory shock, coagulopathy and respiratory failure which contributed to death. ¹⁵ The diagnosis of viral meningitis/encephalitis was made in 50 cases (55.6%), bacterial in 30(33.3%), TBM in 8(8.9%), and Rickettsial and Fungal (candida albicans) meningitis in 1(1.1%) case each. This is similar to study by CM Bokade et al.⁹ in which viral (46.59%), bacterial (22.16%), TBM (15.3%) and cerebral malaria in 15.9% of cases. Also, study done by Huttunen et al.¹⁶, showed comparable results with aetiological agent identified in 56 cases (85%) of which 38% were bacterial meningitis, 45% viral meningitis/encephalitis, 16% neuroborreliosis and 1 child with fungal (Candida albicans) infection. The CSF study in this present study supported the evidence of raised CSF leukocytes mostly>100/cumm., predominantly polymorphs, raised protein and low sugar in bacterial meningitis compared to viral meningitis as is also evident in study conducted by Pandey et al. ¹⁷. CSF Gram staining showed Gram positive cocci and Gram -negative bacilli in 4 cases each out of which 7 cases also showed growth of organism on CSF culture. CSF ZN staining detected AFB in 2 cases while CBNAAT detected mycobacterium in CSF of 1 case and gastric lavage of 1 case. The viral etiology of CNS infection was considered in 50 cases (55.6%) more prevalent in age group of 2-10 years, of which only one case was JE IgM positive. In study conducted by Davies et al.¹⁸ on factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infection found that virus was not detected in 70% cases where viral etiology was thought to be likely, with a consequent negative predictive value (NPV) for the assay of 82.5% and therefore a negative result can only be used with moderate confidence to rule out CNS viral infection. Neuroimaging modalities used were USG skull, CT Brain and MRI. MRI T2/FLAIR studies suggested likely HSV-encephalitis in 3 cases showing hyperintensities in left temporal lobe, right hippocampus, amygdale, left hypothalamus, bilateral para-falcine occipital cortex²⁰ in one of the cases who presented with blindness with prior history of fever and rash. Vasanthapuram et al.²⁰ and Samanta et al.²¹ have in their studies showed the significant role of DENV as an under- recognized causative agent of AES. Chokephaibulkit K et al. ²² conducted a prospective study of Thai children identified viral agents in 26(65%) of 40 children of which Dengue virus(8) was in maximum number of cases followed by JEV (6), HSV (4), (3), mumps(2), enterovirus(1), VZV(1) and rabies(1). SA Karmarkar et al.⁸ conducted a study in which most common viral cause was Enterovirus followed by JEV and HSV. SK Rathore et al.² did a study which showed HSV I or II as most common cause followed by measles, JEV and DENV. Huttumen et al.¹⁶ conducted a study in which enteroviruses were most common accounting for 22% of all viruses and 44% of proven meningitis/encephalitis. Other common viruses were VZV and HHV6. Bacterial meningitis was diagnosed in 30(33.3%) cases, maximum number of cases in age group of 2-5 years followed by less than 1 year of age; of which CSF culture positive were 12(13.3%) cases, blood culture positive 22(24.4%) cases and both CSF and blood culture positive 3 cases (MRSA (2) and Salmonella enteritidis (1)). This lower rate of detection of bacteria in CSF is comparable to study conducted by Garg et al.¹⁰ and Debnath et al. (13.9%)¹¹ which can be attributed to prior use of antibiotic, contamination of blood culture sample and poor quality of blood culture medium. The most common organism isolated in blood was MRSA in 6 cases and in CSF were MRSA, Salmonella enteritidis, Non-fermenters and Pseudomonas aeruginosa in 2 cases each. The cases which did not show growth in both blood and CSF but were diagnosed as bacterial meningitis based on history, clinical features and CSF analysis showing turbidity, predominant polymorphs, raised protein, low sugar levels and positive Gram stain results in few cases. Pyogenic meningitis was most common cause in studies by SA Karmarkar et al.⁸, Garg et al. ¹⁰, Adhikari et al.²³ and Debnath et al.¹¹ where the common bacterial isolates from both CSF and blood were Klebsiella pneumoniae, followed by Non-fermenters and Streptococcus pyogenes. E. coli and Staphylococcus aureus were the most common cause of pyogenic meningitis in the study by Adhikary et al. ²³ as seen in our present study. Tubercular meningitis was diagnosed in 8 (8.9%) cases 5 were in age group of 2-5 years. A history of contact with pulmonary tuberculosis case on antitubercular treatment was found in 4 cases, all of them being parent of the patient. The usual presentation was history of prolonged fever of 10-15days, altered sensorium and convulsions with intermittent posturing. The CSF analysis showed turbidity in 5(62.5%) cases, no cob web and colourless fluid. AFB was detected by ZN staining in 2 cases while CSF CBNAAT and gastric lavage CBNAAT detected Mycobacterium in 1 case each. In 1 case, blood PCR detected mycobacterium. The CSF leukocyte count in most cases was >100/cumm., predominant lymphocytes in all cases, raised protein in 7(87.5%) and low glucose in 7(87.5%) cases. MRI and CT brain showed changes suggestive of tubercular meningitis like basal exudates, infarcts, and communicating hydrocephalous in most of the cases. CSF ADA levels were >10 U/L in 3 cases. The similar prevalence of TBM was found in study by SA Karmarkar et al.⁸ where TBM cases accounted for 7.9% of total cases, while it was higher in study conducted by CM Bokade et al. ⁹ where TBM was diagnosed in 15.3% cases. In this present study Candida albicans was detected from blood culture of 1 patient who was 40 days old and had history of NICU admission in view of sepsis. The patient succumbed due to multiorgan failure. Rickettsial encephalitis was diagnosed in patient based on clinical features of fever with maculopapular rash involving palms and soles, history of contact with cattle, hand and leg oedema, hepatomegaly and blood investigations showing leukocytosis, raised liver transaminases, raised titers of OX-19 and OX-2 on Weil-Felix test and improvement on treatment with Injection Chloramphenicol.

CONCLUSION

In present study most common cause of CNS infection in children was viral meningitis/encephalitis, however below 1 year of age the most common cause is bacterial meningitis. The most common age group affected is below 5 years of age. Since CNS infections can be caused by almost any agent like bacteria, viral, tubercular, fungal, rickettsial; a wide panel of agents should be studied wherever feasible. Treatment with steroids and anticonvulsants should be based on clinical judgement.

REFERENCES

1. Archibald L.K., Quisling R.G. Central Nervous System Infections. In: Layon A., Gabrielli A., Friedman W. (eds) Textbook of Neurointensive Care. Springer, London; 2013. p. 427-517.
2. Rathore SK, Dwibedi B, Kar SK, Dixit S, Sabat J, Panda M. Viral etiology and clinico-epidemiological features of acute encephalitis syndrome in eastern India. Epidemiol. Infect. 2014;142: pp 2514-21.
3. Sahu RN, Kumar R, Mahapatra AK. Central nervous system infection in the pediatric population. J PediatrNeurosci. 2009; 4(1):20-4.
4. John T J, Verghese VP, Arunkumar G, Gupta N, Swaminathan S. The syndrome of acute encephalitis in children in India: Need for new thinking. Indian J Med Res 2017; 146:158-61.
5. Hamid J, Meaney C, Crowcroft N, Granerod J, Beyene J. Potential risk factors associated with human encephalitis: application of canonical correlation analysis. Hamid et al. BMC Medical Research Methodology 2011; 11:120
6. Jmor F, Emsley H, Fischer M, Solomon T, Lewthwaite P. The incidence of acute encephalitic syndrome in western industrialised and tropical countries. Jmor et al. Virology Journal 2008, 5:134
7. Singhi, P., andSankhyan N. Febrile encephalopathy. Journal of the International Child Neurology Association 2018; 1(1), 9.
8. Karmarkarsa, Aneja S, Khare S, Saini A, Seth A, Chauhan B.K.Y. A Study of Acute Febrile Encephalopathy with Special Reference to Viral Etiology. Indian J Pediatr 2008; 75(8): pp 801-805.
9. Bokade CM, Gulhane RR, Bagul AS, Thakre SB. Acute Febrile Encephalopathy in Children and Predictors of Mortality. Journal of Clinical and Diagnostic Research, 2014 Aug, Vol -8(8): PCO9-PC11.
10. Garg A, Sharma A, Kumari S, Shandil A. Clinical profile and outcome of pediatric bacterial meningitis: a prospective study from tertiary institute in Northen India.Int J Res Med Sci 2018; 6:2739-45
11. Debnath DJ, Wanjpe A, Kakrani V, Singru S. Epidemiological study of acute bacterial meningitis in admitted children below twelve years of age in a tertiary care teaching hospital in Pune, India. Med J DY Patil Univ 2012; 5:28- 30.
12. Muenchhoff M, Goulder P. Sex differences in Pediatric Infectious Diseases. The Journal of Infectious Diseases 2014; 209(S3): S120-6.
13. WHO (2007) Departments of Gender, Women and Health, and Epidemic and Pandemic Alert and Response, WHO, Geneva. Addressing sex and gender in epidemic-prone infectious diseases. (https://www.who.int/csr/resources/publications/SexGenderInfectDis.pdf,accessed 2 February 2021).
14. Daniel B, Grace G, Natrajan M. Tuberculous meningitis in children: Clinical management and outcome. A review. Indian J Med Res 2019; pp 117-130.
15. Vasanthapuram R, Hameed S, Desai A, Mani R, Reddy V. Dengue virus is an under-recognised causative agent of acute encephalitis syndrome (AES): Results from a four year AES surveillance study of Japanese encephalitis in selected states of India. International Journal of Infectious Diseases 845(2019): S19-S24.
16. Huttunen P, Lappalainen M, Salo E, Lonnqvist T, Jokela P, Hyypia T, Peltola H. Differential diagnosis of acute central nervous system infections in children using modern microbiological methods. Acta Paediatrica. June 2009; 98: pp 1300-1306.
17. Pandey P, Jha B, Shrestha A. Cytological and Biochemical Profile of Cerebrospinal Fluid from Meningitis Patients. ACCLM 1(1) 2-5(2015).
18. Davies N, Brown L, Gonde J, Irsih D, Robinson R, Swan A, Banatvala J, Howard R, Sharief M, Muir P. Factors infleuncing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections. J Neurol Neurosurg Psychiatry, 2005; 76(1): pp 82-87.
19. Committee on Infectious Diseases American Academy of Pediatrics In. Kimberlin DW, Brady MT, Jackson MA, Long SS. Red Book: Report of the Committee on Infectious Diseases 30th edition. American Academy of Pediatrics, 2015.
20. Vasanthapuram R, Hameed S, Desai A, Mani R, Reddy V. Dengue virus is an under-recognised causative agent of acute encephalitis syndrome (AES): Results from a four year AES surveillance study of Japanese encephalitis in selected states of India. International Journal of Infectious Diseases 845(2019): S19-S24.
21. Samanta M, Kundu CK, Guha G, Chatterjee S. Unique Neurological Manifestations of Dengue Virus in Pediatric Population: A Case Series. Journal of Tropical Pediatrics, 2012; Vol 58(5): pp 398-401.
22. Chokephaibulkit K, Kankirawatana P, Apintanapong S, Pongthapisit V, Yoksan S, Kositanont U, Puthavathana P. Viral etiologies of encephalitis in Thai children. Pediatr Infect Dis J. 2001: 20(2): pp 216-8.
23. Adhikary M, Chatterjee RN. Laboratory evaluation of cases of meningitis attending a tertiary care hospital in India: An observational study. Int J NutrPharmacol Neurol Dis 2013; 3:282-8.