Clinical and laboratory profile of patients with presumptive clinical diagnosis of acute bacterial meningitis and its short-term complications

Abstract

Background:

Worldwide, one million cases of bacterial meningitis are estimated to occur and 200,000 of them die annually. Case fatality rates vary with age at the time of illness and the species of bacterium causing infection. In view of variable clinical features and complication rates in various studies, the present study was planned to assess the clinical and laboratory profile of patients with acute bacterial meningitis and analyze the therapeutic response and short-term sequelae.

Materials:

This study was conducted in the department of pediatrics at Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak. A total of 50 pediatric patients with signs and symptoms of acute bacterial meningitis who satisfied the inclusion or selection criteria were enrolled in the study. Appropriate statistical tests were applied for analysis and trial registry was done with PGIMS.

Results:

In the present study, slightly more males (54%) were found than females (46%). The sequelae and mortality were 33.3%, 26.1% and 7.4%, 8.7% in males and females, respectively. There were higher chances of sequelae or mortality in males as compared to females (OR 1.289, 95% CI 0.073–6.11, P > 0.05). Predominant cells were polymorphonuclear (PMN) cells except in >120 months age group where both PMN (50%) and mononuclear (50%) cells were equally visualized. Mean CSF protein was slightly higher in 2–24 months age group.

Conclusion:

We compared the group with sequelae with the group with no sequelae and found neurological deficit (P < 0.01), and presence of complications (P < 0.01) were significantly associated with sequelae.

Introduction

Meningitis is an infectious disease characterized by infection of leptomeninges and underlying subarachnoid cerebrospinal fluid (CSF). Depending on the onset and symptoms, meningitis may be classified into acute (<1 day), subacute (1–7 days) or chronic (>7 days) categories.[1] Acute bacterial meningitis (ABM) is an important disease of early childhood (0–5 years) with high case fatality and risk of neurological handicaps.[1]

Worldwide, one million cases of bacterial meningitis are estimated to occur and 200,000 of them die annually. Case fatality rates vary with age at the time of illness and the species of bacterium causing infection. Case fatality ranges form 3%–19% in developed countries and 37%–60% in developing countries. Up to 54% of survivors are left with disability due to bacterial meningitis.

In a multicentric survey in India, ABM constituted 1.5% of admissions in pediatric wards and the mean case fatality was 16%.[2] Approximately 30% of newborns with clinical sepsis have associated bacterial meningitis. Since the initiation of intrapartum antibiotics in 1996, a decrease has occurred in the national incidence of early-onset group B streptococcus (GBS) infection from approximately 1.8 cases per 1000 live births in 1990 to 0.32 case per 1000 live births in 2003.[1]

Predisposing factors include respiratory infection, otitis media, mastoiditis, head trauma, hemoglobinopathy, human immunodeficiency virus (HIV) infection, and other immune deficiency states. S. epidermidis and other coagulase-negative staphylococci frequently cause meningitis and cerebrospinal shunt infection in patients with hydrocephalus or following neurosurgical procedures. Immunocompromised children can develop meningitis caused by species of Pseudomonas, Serratia, Proteus, and diphtheroids. Reports from developing countries indicate that a sizeable proportion of cases presumed to be bacterial in nature fail to demonstrate any pathogen.[3,4]

To diagnosis bacterial meningitis, CSF examination is mandatory. CSF culture is considered to be the gold standard for diagnosis, and it is obligatory to obtain the in vitro susceptibility of the causative microorganism and to rationalize treatment.

Mortality rates vary with age and pathogen, with the highest being for S. pneumoniae. Despite effective antimicrobial and supportive therapy, mortality rates among neonates remain high, with significant long-term sequelae in survivors. Bacterial meningitis also causes long-term sequelae and results in significant morbidity beyond the neonatal period. Mortality rates are highest during the first year of life, decreasing in mid-life and increasing again in elderly persons. Despite advances in care for patients with bacterial meningitis, the overall case fatality remains steady at approximately 10%–30%.

In view of variable clinical features and complication rates in various studies, the present study was planned to assess the clinical and laboratory profile of patients with ABM and analyze the therapeutic response and short-term sequelae.

Purpose of study: Knowledge about factors associated with poor prognosis could be valuable in selecting patients for more intensive monitoring and treatment in order to further improve outcome. Several risk factors associated with sequelae in childhood BM have been identified in some studies and needs to be emphasized for future course of management.

Material and Methods

This study was conducted in the department of pediatrics at Pt. B. D. Sharma PGIMS, Rohtak. A total of 50 pediatric patients with signs and symptoms of acute bacterial meningitis who satisfied the inclusion or selection criteria were enrolled in the study.

Inclusion criteria

1. Children 2 months to 14 years of age presented with clinical signs and symptoms of meningitis (fever, vomiting, altered behavior, bulging fontanelle, seizure, meningeal signs)

2. CSF picture:

• CSF leucocytes 100–10,000 per cmm (Usually 300–2000) predominantly neutrophils

• CSF protein 100–500 mg/dl

• CSF sugar <50% of blood sugar.

Exclusion criteria

1. Patient with partially treated meningitis

2. Post-traumatic meningitis including meningitis developing after cranial surgery.

3. Patients already with neurological deficits.

4. Patients with neural tube defects, i.e., meningocele or meningomyelocele

5. Immunocompromised patient including patients with neutropenia

6. Patient with stroke, brain-hypoxia or anoxia

7. Tubercular or fungal meningitis

8. Meningoencephalitis (viral).[5]

Method

A total of 50 patients who satisfied the selection criteria were enrolled in the study. Informed consent was taken from the parents of all participants. The nature of the process and trial was explained to the parents of participants. Baseline data was collected including name, age, sex, date of admission, telephone number, housing, socioeconomic status, clinical sign and symptoms. Trial registry was with PGIMS, Rohtak Haryana.

Investigations

Basic investigations included complete blood count (CBC), chest X-ray, serum electrolytes and blood culture and sensitivity (C/S), C-reactive protein (CRP). Radiological investigation like ultrasound skull was done in infants with open anterior fontanelle. Contrast enhanced computed tomography (CECT) head or MRI brain was considered in patients with (i) signs of increased intracranial tension, (ii) focal neurological deficits, (iii) prolonged fever during therapy, (iv) recurrent or focal seizures, (v) prolonged depression of consciousness, and (vi) increased head circumference.[6] Serum glucose was measured simultaneously just before LP. Sample for blood sugar was taken in fluorinated vial. Lumbar puncture was done of all enrolled patients. Under all aseptic conditions, 3 ml of CSF was taken in three sterile vials and was analyzed for

1. biochemical examination for protein and sugar

2. total and differential cell count

3. microbiological assays including Gram staining, microscopic examination and culture sensitivity

Follow-up

Patients who recovered were regularly followed up in the outpatient department (OPD) at 1 and 6 months. Evaluation on follow-up included detailed neurological examination, audiometry, brainstem evoked response audiometry (BERA), vision testing, test for development quotients (Denver Developmental Screening Test),[7] and intelligence quotients. Data were prepared regarding patient’s condition at discharge, at 1 month and 6 months for response to antibiotic therapy and short-term complications and sequelae, if any.

Statistical analysis

Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS®) version 16. Data on children developing sequelae were compared with data on children with no sequelae to identify the variables having significant association with sequelae. The Chi-squared test with 0.05 level of significance and Fischer’s t test were applied for qualitative analysis of variables.

Results

This study was conducted in the department of pediatrics at Pt. B. D. Sharma PGIMS, Rohtak. A total of 50 pediatric patients with signs and symptoms of acute bacterial meningitis who satisfied the inclusion or selection criteria were enrolled in the study.

Table 1 shows that there were 27 children (54%) who developed complications, of which persistent seizures (37%) and peripheral circulatory failure (37%) were most common followed by hemi/quadriparesis, cranial nerve palsy, hearing loss and hydrocephalus. The sequelae and mortality in children with persistent seizures and peripheral circulatory failure were 30%, 20% and 10%, 40%, respectively. Development of any complications (OR 9.7, 95% CI 2.3–40.8) during hospital stay was strongly associated with development of sequelae or mortality as final outcome. This association was found to be statistically significant (P = 0.001).

Table 1.

Complications (n=27)

Complications	No. of cases n (%)	Sequelae	Mortality
Persistent seizure	10 (37%)	5	1
Extra-axial fluid collection	0	0	0
Cranial nerve palsy	3 (11.1%)	2	0
Hearing loss	3 (11.1%)	3	0
Hydrocephalus	3 (11.1%)	2	0
Hemi/Quadriparesis	4 (14.8%)	3	0
Peripheral circulatory failure	10 (37%)	2	4
DIC	2 (7.4%)	0	2
SIADH	0	0	0
Arthritis	0	0	0
Cortical blindness	1 (3.7%)	1	0

Most common abnormal findings were low hemoglobin (Hb) (60%), high total leukocyte count (TLC) (50%) and neutrophilia (46%). There were only two children (4%) with hyponatremia and one child (2%) with abnormal PTI/PTTK. The association of sequelae and mortality with low Hb, high TLC and neutrophilia were 40%, 32%, 34.8% and 13.3%, 8%, 8.7%, respectively.

Table 2 shows that therapeutic response in CSF examination at 48 hours was evident in terms of decrease in total cell count, decrease in polymorphonuclear cells with increase in mononuclear cells and lymphocytes, decrease in proteins and increase in sugar. The response at the end of therapy was seen in terms of disappearance of cells in 50% of children, and in the rest, very few number of cells, fall of proteins within normal range and increase in sugar were seen. However, Gram staining and culture sensitivity was negative in all children in our study.

Table 2.

CSF examination at admission, at 48 hours and at discharge

CSF Examination	At admission n=50	At 48 Hours n=47	At discharge n=46
Increased pressure	16 (32%)	0	0
Total cell count/cmm (mean±SD)	902.1±1465.8	642.5±1053.2	2.5±3.2
No cells/cmm	0	2 (4.26%)	23 (50%)
<100 cells/cmm	0	0	23 (50%)
100-500 cells/cmm	34 (68%)	33 (70.2%)	0
500-1000 cells/cm	5 (10%)	1 (2.13%)	0
>1000 cells/cmm	11 (22%)	11 (23.4%)	0
Predominant cells
PMN	33 (66%)	21 (44.7%)	1 (2.17%)
MN	13 (26%)	19 (40.4%)	9 (19.56%)
L	4 (8%)	5 (10.6%)	13 (28.26%)
Gram Staining Positive	No	No	No
Culture Sensitivity
Positive	No	No	No
Proteins (mean±SD)	197.4±94.8	138.6±68.1	47.2±14.7
Sugar (mean±SD)	59.2±25	65.4±25.5	75.2±18.1

In our study, 10 children showed abnormal CT findings, of which hydrocephalus and infarct were common. There was only one child with abnormal MRI finding and no child with abnormal ultrasonography (USG) examination. The sequelae and mortality were 50%, 100% and 10%, 0% in children with abnormal CT and MRI, respectively. There were high chances of poor outcome in relation to abnormal CT or MRI findings (OR 3.12, 95% CI 0.75–13). This association was not statistically significant (P = 0.15). The case fatality was 8% while sequelae were present in 30% of children. There were 62% of children who survived without any sequelae and with complete recovery. There were seven children with secondary nosocomial infection, of which malaria and lower respiratory tract infection were common. The sequelae were seen in only one child with secondary nosocomial infection (malaria), while there was no associated mortality. There was no association of secondary nosocomial infection (OR 0.23, 95% CI 0.03–2.1). There were 15 children with sequelae, of which resistant seizure and sensorineural hearing loss were common followed by visual impairment and motor deficit.

There were 25 children (50%) with Glasgow coma scale (GCS) of <15 in our study, of which five children (10%) were with GCS score of <8. Complications were present in 90% children with GCS score of <8 and in 65% of children with GCS score of 8–14.

As discussed in Table 3, there was male predominance in 2–24-month and >120-month age groups. Abnormalities belonged to rural background (80%) (OR 1.88, CI 0.52–6.85) in 2–24 months as compared to other two groups. At admission, seizure was the main presenting complaint in 2–24-month (92%) and 25–120-month (84.2%) group, whereas seizure (50%) and altered consciousness were leading presenting complaints in age group >120 months. Motor deficit (15.8%) and malnutrition (21%) were more evident in 24–120-month age group as compared to other age groups. Sick general condition on admission (83.3%), abnormal neurological examination and presence of meningeal signs (83.3%) were more commonly encountered in >120-month age group. Focal neurological deficits and raised intracranial pressure (33.3%) were also more frequent in this group. Complications (63.16%) during hospital course were more evident in 25–120-month age group. Mean TLC was slightly lower in the >120-month group. Hyponatremia (8%) was more frequent in 2–24-month group (OR 5.43, CI 0.25–119.05). Also, there were more radiological abnormalities (31.6%) in the 24–120-month age group.

Table 3.

Comparison of demographic profile, sign/symptoms, complications and laboratory findings of three different age groups

Factors	2–24 months (n=25)	25-120 months (n=19)	> 120 months (n=6)	Odds ratio (95% CI)	P
Male gender	14 (56%)	9 (47.4%)	4 (66.7%)	1.18 (0.39-3.58)	1.00
Rural background	20 (80%)	13 (68.42%)	4 (66.7%)	1.88 (0.52-6.85)	0.52
At admission
Seizures	23 (92%)	16 (84.2%)	3 (50%)	3.63 (0.66-20.1)	0.25
Altered consciousness	2 (8%)	5 (26.3%)	3 (50%)	0.19 (0.04-0.98)	0.07
Motor deficit	0	3 (15.8%)	0	0.13 (0.01-2.58)	0.24
Severe malnutrition	1 (4%)	4 (21%)	1 (16.7%)	0.17 (0.02-1.55)	0.19
GPE - Sick	8 (32%)	8 (42.1%)	5 (83.3%)	0.43 (0.14-1.37)	0.25
GCS <8	1 (4%)	2 (10.53%)	2 (33.3%)	0.22 (0.02-2.12)	0.35
Abnormal pupils	7 (28%)	6 (31.6%)	3 (50%)	0.69 (0.2-2.29)	0.76
Abnormal fundus	0	3 (15.8%)	2 (33.3%)	0.07 (0.004-1.4)	0.05
Abnormal tone	5 (20%)	7 (36.84%)	3 (50%)	0.38 (0.11-1.33)	0.22
Abnormal power	1 (4%)	10 (52.6%)	3 (50%)	0.04 (0.005-0.33)	0.0003
Abnormal reflexes	8 (32%)	4 (21%)	4 (66.7%)	1.00 (0.31-3.28)	1.00
Meningeal signs	7 (28%)	15 (79%)	5 (83.3%)	0.1 (0.03-0.36)	0.0005
During hospitalization
Cranial nerve involvement	1 (4%)	2 (10.53%)	1 (16.7%)	0.31 (0.03-3.16)	0.61
Focal neurological deficit	1 (4%)	5 (26.3%)	2 (33.3%)	0.11 (0.01-0.95)	0.049
Raised intracranial pressure	5 (20%)	4 (21%)	2 (33.3%)	0.79 (0.21-3.03)	1.00
Complications	12 (48%)	12 (63.16%)	3 (50%)	0.62 (0.2-1.9)	0.57
During hospitalization
Blood total leucocyte counts/cmm (mean±SD)	12548±5231.7	12457.9±4184.5	10450±2001.7	0.59
Hyponatremia	2 (8%)	0	0	5.43 (0.25-119.05)	0.49
Hypocalcemia	1 (4%)	1 (5.26%)	0	1.00 (0.06-16.94)	1.00
Abnormal PTI/PTTK	1 (4%)	0	0	3.12 (0.12-80.5)	1.00
Abnormal CT	3 (12%)	6 (31.6%)	1 (16.7%)	0.35 (0.08-1.55)	0.29

Mean TLC was higher in the 2–24-month age group. A majority of cases, that is, 17 (68%), 12 (63.12%) and 5 (83.3%) cases in age groups of 2–24 months, 24–120 months and >120 months, respectively, had cell count in the range of 100–500 cells/cmm. Predominant cells were polymorphonuclear (PMN) cells except in >120-month age group where both PMN (50%) and mononuclear (50%) cells were equally visualized. Mean CSF protein was slightly higher in 2–24-month age group. Mean CSF sugar and CSF/blood sugar ratio were also low in 2–24-month age group as compared to other groups.

Discussion

Bacterial meningitis is a serious, often disabling and potentially fatal infection resulting in 170,000 deaths worldwide each year.[1] Young children are particularly vulnerable to bacterial meningitis and when exposed poor outcomes may occur due to the immaturity of their immune systems. Two thirds of meningitis deaths in low-income countries occur among children under 15 years of age.[1] Serious, long-term neuropsychological sequelae further increase the population impact of pediatric meningitis. Sequelae comprise a range of findings with implications for child development and functioning and include such deficits as hearing loss, vision loss, cognitive delay, speech or language disorder, behavioral problems, motor delay or impairment, and seizures.[8,9]

The spectrum of neurological sequelae in our study was resistant seizure, sensorineural hearing loss, motor deficit, visual impairment and cranial nerve palsy. Most common neurological sequelae seen in the present study was resistant seizures (33.3%). Namani et al.[10] also found resistant seizures (66.7%) as the most common neurological sequelae in their study followed by hydrocephalus, deafness, neuropsychiatric impairment and motor deficit. But Singhi et al. found severe mental retardation (21.1%) as most common sequelae. Incidence of severe sensorineural hearing loss (26.1%) seen in our study was within the range which had been reported earlier (5.6%–30%).[6,9,10,11,12] Cherian B et al.[13] from Ludhiana reported 21.8% of sensorineural hearing loss, which is similar to our study.

In our study, the presence of cranial nerve palsy, focal neurological deficit and development of complications during hospital stay were independent predictors of sequelae in children with acute bacterial meningitis. Pelkonen et al.[14] found presence of symptoms for more than three days (P = 0.02), impaired consciousness (P < 0.01) and convulsions during hospitalization (P < 0.01) as independent predictors of sequelae at follow-up. Singhi et al.[11] found GCS < 8 (P < 0.01), presence of cranial nerve palsy (P < 0.01) and abnormal deep tendon reflexes (P < 0.01) as independent predictors of sequelae at follow-up.

In our study, when we divided the study group into three different age groups (2–24 months, 25–120 months and > 120 months), we found that abnormal power (P < 0.01), presence of meningeal signs (P < 0.01) and focal neurological deficit (P = 0.049) were significantly associated with acute bacterial meningitis in the age group of 2–24 months as compared to other age groups. Presence of seizures at admission (OR = 3.6) and hyponatremia (OR = 5.43) were found to be highly associated with ABM in the 2–24-month age group but not statistically significant. Vasilopoulou et al.[15] showed that infants less than one year of age presented more commonly with seizures, bulging fontanelle, grunting and poor feeding, while children above two years of age manifested more often with meningeal signs, headache, vomiting and hemorrhagic rash. Fever was common for all age groups.

We compared the group with sequelae with the group with no sequelae and found that neurological deficit (P < 0.01) and presence of complications (P < 0.01) were significantly associated with sequelae. We also found that age <24 months (OR = 2.13), presence of fever (OR = 3.8), seizure (OR = 6.43), malnutrition (OR = 3.63), abnormal tone (OR = 3.65), cranial nerve involvement (OR = 4.6) and abnormal CT (OR = 3.38) were highly associated with sequelae at follow-up. Singhi et al.[11] found seizures (P = 0.015), GCS <8 (P = 0.044), presence of cranial nerve palsy (P < 0.01), abnormal reflexes (P < 0.01), positive CSF culture (P = 0.019), abnormal USG head (P = 0.011) and abnormal CT (P < 0.01) to be significantly associated with sequelae at follow-up. Pelkonen et al.[14] found that long duration of illness (P = 0.04), seizures (P = 0.01), very low weight for age (P = 0.02), poor general condition (P = 0.04), impaired consciousness (P < 0.01) and GCS <8 (P < 0.01) were significantly associated with sequelae at follow-up. Chao et al.[16] found seizures and focal neurological signs associated with higher rate of sequelae. Vasilopoulou et al.[15] found that seizures, absence of petechiae, low CSF glucose, high CSF protein and a positive blood culture had a significantly increased risk for sequelae.

Summary and Conclusion

Out of the 50 children enrolled in our study, half were in the age group of 2–24 months (50%) while only 6 children were in >120 months age group. The sequelae and mortality were 40%, 26.3%, 0% and 0%, 5.26%, 50% in 2–24 months, 25–120 months and >120 months, respectively. Mean age at presentation was 50.35 ± 7.162 m, and median age was 27 months. There was higher association of development of sequelae in age group of 2–24 months as compared to other age groups (OR 1.19, 95% CI 0.38–3.72). However, this association was not statistically significant (P = 1.00).

In the present study, slightly more males (54%) were found than females (46%). The sequelae and mortality were 33.3%, 26.1% and 7.4%, 8.7% in males and females, respectively. There were higher chances of sequelae or mortality in males as compared to females (OR 1.289, 95% CI 0.073–6.11, P > 0.05).

There were three-fourth children (74%) who came from rural area, while the rest 26% came from urban area. The sequelae and mortality were 29.7%, 30.8% and 5.4%, 15.4% in rural and urban area, respectively. Although number of cases were more from rural background, it did not affect the development of sequelae depicted by odds ratio 0.632 difference was statistically insignificant (P = 0.5213).

Almost half of the children came in the winter season followed by rainy and summer. The sequelae and mortality were 39.1%, 31.6%, 0% and 8.7%, 0%, 25% in winter, rainy and summer seasons, respectively. There were higher chances of development of sequelae when presentation was during winter season (OR 2.177). This relation was found to be statistically significant (P = 0.010).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.