Epidemiological trends and neurological outcomes of pediatric central nervous system infections in rural part of western India

Abstract

BACKGROUND

Central nervous system (CNS) infections remain a leading cause of morbidity, mortality, and disability among children in low-income and middle-income countries. In India, regional variations in etiology and outcomes are influenced by vaccination uptake, environmental conditions, and healthcare access. Data from rural western India remains limited.

AIM

To evaluate the epidemiological trends, clinical spectrum, etiological distribution, and short-term outcomes of pediatric CNS infections, and to identify factors associated with adverse neurological outcomes.

METHODS

This retrospective study included 278 children (1 month to 12 years) admitted with CNS infections between January 2021 and April 2025. Cases were classified as bacterial meningitis, viral encephalitis, tuberculous meningitis (TBM), brain abscess, or undetermined etiology, based on clinical, laboratory, and neuroimaging criteria. Outcomes were categorized as recovery, neurological sequelae, or death. Data were analyzed for demographic distribution, seasonal patterns, and temporal trends.

RESULTS

The mean age was 5.8 years; 51.1% were < 5 years old, and males accounted for 58.3%. Viral encephalitis was the leading etiology (39.9%), followed by bacterial meningitis (30.9%), TBM (15.1%), brain abscess (2.2%), and undetermined (11.9%). Seasonal clustering occurred during monsoon/post-monsoon months (41.7%). Mortality was 9.4% overall, highest in TBM (21.4%) and bacterial meningitis (12.8%), while viral encephalitis had the lowest (2.7%). Neurological sequelae affected 14.0% of children, predominantly after TBM and bacterial meningitis. Over time, bacterial meningitis declined (31%-21%), while viral encephalitis increased (34%-42%). Children aged < 5 years were more likely to have poor outcomes (P = 0.03). Mortality was highest in TBM (21.4%, P = 0.01), followed by bacterial meningitis (11.4%).

CONCLUSION

Pediatric CNS infections in rural India show shifting trends, with viral encephalitis surpassing bacterial meningitis. Strengthening vaccination coverage, early diagnosis, and hospital preparedness can reduce morbidity and mortality associated with pediatric CNS infection.

Key Words: Pediatric central nervous system infections; Meningitis; Encephalitis; Tuberculous meningitis; Rural India; Epidemiology; Neurological sequelae

Core Tip: This study from the rural part of western India provides an analysis of pediatric central nervous system infections from resource limited setting. Viral encephalitis has overtaken bacterial meningitis as the leading cause, while tuberculous meningitis remains fatal with high disability. Seasonal clustering during the monsoon highlights environmental influences on transmission of disease. The findings emphasize the need for improved vaccination, vector control, rapid diagnostics, and rural neurocritical and rehabilitation services to reduce mortality and long-term sequelae.

INTRODUCTION

Infections of the central nervous system (CNS) – such as meningitis, encephalitis, brain abscess, and tuberculous meningitis (TBM) – continue to be major causes of illness and death among children worldwide. Despite progress in antimicrobial treatments, vaccination efforts, and neurocritical care, these diseases result in significant hospitalizations, fatalities, and lasting neurological impairments, especially in low and middle-income countries (LMICs)[1,2].

Worldwide, acute bacterial meningitis remains a major cause of morbidity and mortality among children under five years of age, particularly in regions where routine immunization against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis has not yet been fully implemented in national programs. In such settings, limited vaccine coverage, delayed diagnosis, and restricted access to tertiary care contribute substantially to the high case-fatality rates and long-term neurological sequelae associated with these infections[3,4].

Globally and in India, the principal bacterial pathogens causing paediatric meningitis include Escherichia coli, Hib, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus, Staphylococcus aureus, and Listeria monocytogenes[3]. The relative frequency varies by age and geographic region, and meningococcal disease can account for a substantial proportion of cases during outbreaks; pooled estimates from India report meningococcal meningitis prevalence of approximately 12.1% (95%CI: 5.2-21.4) when epidemic and endemic settings are combined[5].

Bacterial meningitis is associated with a significant number of child deaths. Outbreaks of viral encephalitis, including Japanese encephalitis (JE), enteroviruses, and other arboviruses, are common in low- and middle income countries. In countries like India, where tuberculosis (TB) is common, TBM is a big challenge due to delayed diagnosis, high mortality rates, and permanent neurological damage. Although less common, brain abscesses can develop due to untreated or inadequately treated conditions such as otitis media or sinusitis[6,7].

Within India, diverse geography and socioeconomic heterogeneity lead to regional variations in disease epidemiology. Multiple multicenter studies in urban and semi urban centers have described bacterial meningitis burden, yet data from rural western India are limited. Rural areas often face poorer sanitation, lower vaccination uptake, delayed care seeking, nutritional deficits, and limited access to diagnostics and neuroimaging, all contributing to worse outcomes[8,9].

Epidemiological surveillance is very critical in CNS infections. Documentation of changes in etiologic patterns – particularly after the introduction of Hib, pneumococcal conjugate vaccine (PCV-13), and JE vaccination – is a must to modify prevention strategies, including immunization. Also, monitoring seasonal and temporal trends helps in anticipating healthcare demands and deciding vector control efforts. Third, recognizing clinical predictors of poor outcomes of the CNS infection supports effective management[10,11].

Over the past two decades, India has observed shifts in CNS infections. The Hospital-Based Sentinel Surveillance for Bacterial Meningitis showed Streptococcus pneumoniae and Hib as leading bacterial pathogens in children under-five, with many serotypes covered by PCV1. Studies have documented that JE/AES cases display strong seasonality and high case fatality, particularly in rural areas. TBM studies show consistently high mortality and sequelae, especially among those with delayed diagnosis or severe disease stage[12,13].

This study was conducted in the rural western region of India, an agrarian population with monsoon-linked disease patterns and limited access to tertiary care. The area represents a true epidemiological cross-section of rural pediatric illness, making it suitable for evaluating temporal and etiological trends in CNS infections.

Given this background, the current study was designed to analyze epidemiologic trends, clinical profiles, etiologies, and short-term outcomes of pediatric CNS infections in a cohort of 278 children admitted to a tertiary care hospital in rural western India during January 2021 and April 2025. The goal was to generate data to inform clinical and public health strategies in similar settings.

MATERIALS AND METHODS

Study design and setting

The present study was a retrospective analysis carried out at the Department of Pediatrics, NAMO Medical Education and Research Institute and NAMO Hospital, a tertiary care teaching hospital in the rural part of western India. This is the referral center for various pediatric patients, delivering care to about 12 Lakh people across surrounding villages and semi-urban areas. The study was conducted from January 1, 2021 to April 30, 2025. A total of 278 pediatric patients who met the eligibility criteria were included.

Ethical approval

The research protocol obtained approval from the Institutional Ethics Committee under letter number NAMOMERI-SVBCH/IEC/2023-24/218. Given the retrospective nature of record review and anonymized data handling, the committee granted a waiver of informed consent.

Inclusion and exclusion criteria

Children included in this study were between the ages of 1 month and 12 years and carried a clinical diagnosis of CNS infection. To ensure diagnostic accuracy, eligibility required at least one supporting criterion. These criteria included cerebrospinal fluid (CSF) findings suggestive of infection, such as pleocytosis, altered protein or glucose levels, or positivity on culture or polymerase chain reaction (PCR). In other cases, neuroimaging evidence consistent with meningitis, encephalitis, or brain abscess was accepted. Where advanced diagnostic testing was unavailable, children were included if there was a strong clinical suspicion of CNS infection based on the overall presentation and the treating physician’s judgment.

Certain patients were excluded from the analysis. These included neonates with meningitis, as such cases were managed separately by the neonatal services. Children with CNS manifestations attributable to non-infectious causes, such as trauma, metabolic encephalopathy, malignancy, or toxin exposure, were also excluded. In addition, cases with incomplete or missing essential clinical and laboratory data were not considered for inclusion.

Laboratory investigations

Microbiological tests included CSF Gram stain and culture, CSF cell count, CSF protein and glucose level, and viral PCR or serology when available. Multiplex CSF PCR panels were not available for the study period; results were recorded, and their effect on antimicrobial/antiviral therapy was evaluated. Due to resource-limited settings, molecular testing coverage was incomplete and is acknowledged as a limitation.

Etiology classification

On the bases of clinical, laboratory, and imaging findings, cases were categorized into etiological groups as follows: (1) Bacterial meningitis (either culture-positive or consistent CSF biochemistry with clinical response); (2) Viral encephalitis [paracoccidioidomycosis/serology positive or fulfilling World Health Organization (WHO) clinical criteria]; (3) TBM (combining CSF findings, imaging, and therapeutic response); (4) Brain abscess (based on neuroimaging); and (5) Undetermined (when no firm etiology could be assigned).

Acute encephalitis syndrome classification

Acute encephalitis syndrome (AES) was defined according to WHO criteria (acute onset of fever with change in mental status and/or new onset seizures). AES cases were classified as: (1) Neurologic AES – where CSF PCR/serology or neuroimaging supported a primary neurotropic viral etiology (e.g., herpes simplex virus, JE, West Nile virus); and (2) Systemic AES – where laboratory testing suggested a systemic infectious cause with secondary CNS involvement (e.g., scrub typhus, malaria, dengue, chikungunya). Diagnostic tests used included CSF viral PCR (where available), serum/CSF immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) for JE and dengue, blood smear/antigen testing for malaria, and rickettsial serology for scrub typhus.

Treatment and outcome assessment

Therapeutic interventions were recorded, including empirical antibiotic therapy, antiviral agents, anti-tubercular therapy, and intensive care unit (ICU) admission where needed. The clinical outcome at discharge was classified as complete recovery, in-hospital death, or survival with neurological sequelae (persistent seizures, motor deficits, or cognitive impairment).

Statistical analysis

Using a standardized proforma, trained investigators extracted relevant data from the hospital records. Demographic variables included age, sex, residence, and socioeconomic status. The month of admission was used to analyze seasonal distribution. Clinical presentations – such as fever, seizures, altered sensorium, headache, vomiting, meningeal signs, and focal neurological deficits – were recorded. Laboratory investigations comprised hematology, biochemistry, CSF analysis (including cell count, protein, glucose), microbiological cultures, viral PCR or serology when available, and neuroimaging (computed tomography or magnetic resonance imaging of the brain).

Cases were classified as having an undetermined etiology when both CSF culture/PCR and neuroimaging were inconclusive, but clinical features strongly suggested CNS infection. Missing or incomplete datasets were excluded from inferential analysis; no imputation was performed. Binary logistic regression using the backward stepwise method (variables with P < 0.1 in univariate analysis or of clinical relevance) was performed to identify independent predictors of mortality or neurological sequelae. Statistical analysis was done using software SPSS, version 25.0.

RESULTS

As shown in Table 1, the mean age of children affected by CNS infections was 5.8 ± 3.2 years, with more than half of the cases (51.1%) occurring in children under the age of five. A male predominance was noted, accounting for 58.3% of the study population. Seasonal distribution revealed a distinct pattern, with the highest proportion of cases (41.7%) presenting during the monsoon and post-monsoon months (July-October). Winter contributed 29.9% of admissions, while summer months (March-June) accounted for 28.4%. These findings suggest that younger children, particularly males, were disproportionately affected, and environmental factors such as rainfall and seasonal variation played a significant role in disease burden.

Table 1 Demographic and seasonal characteristics of pediatric central nervous system infections in children (n = 278), n (%)/mean ± SD.

Variable
Mean age (years)	5.8 ± 3.2
Age < 5 years	142 (51.1)
Male sex	162 (58.3)
Monsoon/post-monsoon (July-October)	116 (41.7)
Winter (November-February)	83 (29.9)
Summer (March-June)	79 (28.4)

Table 2 indicates that viral encephalitis was most the common cause of pediatric CNS infections, accounting for 39.9% of all cases. Bacterial meningitis was the second most common etiological cause, contributing to 30.9% of cases, followed by TBM, which was responsible for 15.1% cases. Brain abscesses were relatively less common, representing only 2.2% of the cases. 11.9% of cases remained undetermined despite all available investigations, reflecting the diagnostic challenges in resource-limited rural settings.

Table 2 Etiological spectrum of pediatric central nervous system infections.

Etiology	Cases (n)	Percentage, %
Viral encephalitis	111	39.9
Bacterial meningitis	86	30.9
Tuberculous meningitis	42	15.1
Brain abscess	6	2.2
Undetermined	33	11.9
Total	278	100.0

Values represent the number of cases and their corresponding percentages of the total cohort.

Table 3 summarizes the clinical outcomes for different causes of pediatric CNS infections. Overall, 76.6% of the children recovered without any long-term effects, whereas 14.0% developed lasting neurological issues, and 9.4% died (a total of 26 deaths). The outcomes varied significantly based on the etiology. Viral encephalitis showed the best prognosis, with 88.3% recovery and a low death rate of 2.7%. Conversely, bacterial meningitis had higher rates of death (12.8%) and neurological sequelae (11.6%). TBM had the poorest outlook, with only 57.1% recovering and high rates of both sequelae and mortality at 21.4%. Brain abscesses had relatively good survival, with no reported deaths, though 16.7% experienced sequelae. For cases with unknown causes, outcomes were intermediate, with 63.6% recovering, 27.3% developing sequelae, and 9.1% dying (Figure 1).

Figure 1 Clinical outcomes by etiology among children with central nervous system infections. Stacked bar chart presenting outcome categories – full recovery, neurological sequelae, and mortality – for each major etiology. Viral encephalitis shows the highest recovery rate, while tuberculous meningitis is associated with the highest proportions of sequelae and mortality. CNS: Central nervous system; TBM: Tuberculous meningitis.

Table 3 Outcomes by etiology of pediatric central nervous system infections, n (%).

Etiology	Recovered	Neurological sequelae	Deaths
Viral encephalitis	98 (88.3)	10 (9.0)	3 (2.7)
Bacterial meningitis	65 (75.6)	10 (11.6)	11 (12.8)
Tuberculous meningitis	24 (57.1)	9 (21.4)	9 (21.4)
Brain abscess	5 (83.3)	1 (16.7)	0 (0.0)
Undetermined	21 (63.6)	9 (27.3)	3 (9.1)
Total	213 (76.6)	39 (14.0)	26 (9.4)

Values represent the n (%) of children in each outcome category according to infection etiology. Percentages are based on the total within each etiological group.

Table 4 summarizes the neurological sequelae observed among survivors of pediatric CNS infections. Neurological sequelae were identified in 39 of 213 survivors (18.3%). Post-infectious epilepsy was the most frequent sequela (15 cases; 7.0%), followed by hemiparesis (9 cases; 4.2%), cognitive impairment (8 cases; 3.8%), and cerebral palsy (5 cases; 2.3%). Spinal deformities were infrequent (2 cases; 0.9%). These sequelae primarily represented post-meningitis and post-encephalitic complications detected at hospital discharge.

Table 4 Neurological sequelae among survivors of pediatric central nervous system infections (n = 213), n (%).

Neurological sequelae	Cases
Post-infectious epilepsy	15 (7.0)
Hemiparesis	9 (4.2)
Cognitive impairment	8 (3.8)
Cerebral palsy	5 (2.3)
Spinal deformities	2 (0.9)
Total neurological sequelae	39 (18.3)

Percentages are calculated using the total number of survivors at discharge (n = 213).

Table 5 presents the results of the univariate analysis examining clinical and demographic factors associated with mortality and neurological sequelae in children with CNS infections. Younger age (< 5 years) was significantly associated with higher mortality (12.6% vs 6.2%, P = 0.04), although the difference in sequelae rates did not reach statistical significance (16.9% vs 11.1%, P = 0.09). Sex was not a significant determinant of outcome, with comparable mortality (8.6% in males vs 10.3% in females, P = 0.64) and sequelae rates (13.0% vs 15.5%, P = 0.55). The presence of altered sensorium at admission was a strong predictor of poor prognosis, with markedly higher mortality (18.9% vs 4.8%, P = 0.002), although its association with sequelae did not reach significance (17.1% vs 11.4%, P = 0.12). Seizures, while not significantly linked to mortality (11.3% vs 8.0%, P = 0.28), were strongly associated with an increased risk of sequelae (21.7% vs 8.3%, P = 0.01).

Table 5 Univariate analysis of factors associated with mortality and neurological sequelae in pediatric central nervous system infections.

Variable	Deaths	Neurological sequelae (%)
Age < 5 years	12.6a	16.9
Age ≥ 5 years	6.2	11.1
Male sex	8.6	13.0
Female sex	10.3	15.5
Altered sensorium present	18.9b	17.1
No altered sensorium	4.8	11.4
Seizures present	11.3	21.7a
Seizures absent	8.0	8.3

^aP < 0.05 (χ² test).

^bP < 0.01 (χ² test).

Values represent the percentage of deaths and neurological sequelae among each subgroup. Data with P > 0.05 are not indicated.

Over the four-year study period, a clear shift in the etiological trends of pediatric CNS infections was observed. The proportion of bacterial meningitis cases demonstrated a steady decline, dropping from 31% in 2021 to 21% by 2025, likely reflecting the impact of improved vaccine coverage and preventive measures. In contrast, viral encephalitis cases showed a gradual rise, increasing from 34% in 2021 to 42% in 2025, highlighting the growing recognition and burden of viral pathogens, particularly arboviruses, in this region. TBM remained relatively stable at around 15% throughout the study period, underscoring its persistent contribution to morbidity and mortality despite ongoing TB control programs (Figure 2).

Figure 2 Trends in etiological distribution of pediatric central nervous system infections. Line graph showing annual proportions of major etiological categories, including bacterial meningitis, viral encephalitis, tuberculous meningitis, brain abscess, and undetermined cases. Viral encephalitis shows a rising trend over the study period, whereas bacterial meningitis demonstrates a gradual decline. CNS: Central nervous system.

As shown in Figure 3, the seasonal distribution of pediatric CNS infections demonstrated a clear clustering during the monsoon and post-monsoon months, which together contributed 41.7% of cases. Winter accounted for 29.9% of admissions, while summer contributed the remaining 28.4%. This seasonal trend suggests a strong influence of climatic factors on disease transmission, particularly vector-borne viral encephalitis, which tends to surge during periods of heavy rainfall and waterlogging.

Figure 3 Seasonal distribution of pediatric central nervous system infection cases. Bar chart depicting the distribution of cases across three seasonal categories: (1) Monsoon/post-monsoon (July-October); (2) Winter (November-February); and (3) Summer (March-June). The highest concentration of cases occurred during monsoon and post-monsoon months. CNS: Central nervous system.

Multivariate logistic regression analysis identified several independent predictors of poor outcomes among children with CNS infections (Table 6). Age below five years, altered sensorium at presentation, and a diagnosis of TBM were significantly associated with increased risk of either death or neurological sequelae.

Table 6 Independent predictors of poor outcomes (death or neurological sequelae) among children with central nervous system infections.

Variable	Adjusted odds ratio (95%CI)	P value
Age < 5 years	2.31 (1.10-4.89)	0.026
Altered sensorium at admission	3.84 (1.75-8.41)	0.001
Tuberculous meningitis	4.97 (1.92-12.81)	0.001
Bacterial meningitis	2.15 (0.96-4.84)	0.062
Seizures at presentation	1.39 (0.69-2.81)	0.350
Male sex	1.12 (0.53-2.33)	0.770

Multivariate binary logistic regression was performed using the backward stepwise method, including variables with P < 0.1 on univariate analysis or of clinical relevance. Odds ratios are presented with 95%CI. P < 0.05 was considered statistically significant.

Children aged < 5 years had 2.3 times higher odds of poor outcome compared to older children [adjusted odds ratio (aOR) of 2.31; 95%CI: 1.10-4.89; P = 0.026]. The presence of altered sensorium on admission was an even stronger predictor, with an aOR of 3.84 (95%CI: 1.75-8.41; P = 0.001), emphasizing the critical role of early neurological status in outcome determination. Among etiological categories, TBM carried the highest risk, with an aOR of 4.97 (95%CI: 1.92-12.81; P = 0.001) for mortality or sequelae compared to viral encephalitis. In contrast, viral encephalitis had a relatively favorable prognosis with the lowest case-fatality rate (2.7%). Bacterial meningitis showed an intermediate risk (aOR of 2.15; 95%CI: 0.96-4.84; P = 0.062), suggesting a borderline but clinically relevant association.

DISCUSSION

This four-year retrospective study provides valuable insights into the epidemiological trends, clinical spectrum, etiologies, and short-term outcomes of pediatric CNS infections in a rural population of western India. By analyzing 278 children admitted between January 1, 2021 and April 30, 2025, our study contributes to the limited body of literature from rural Indian settings and highlights important shifts in etiological trends, seasonal clustering of cases, and the persistently high mortality and neurological sequelae that accompany these infections. Despite significant advances in diagnostic techniques and therapeutic approaches, pediatric CNS infections continue to impose a heavy burden on resource-constrained rural hospitals.

In this study, etiological classification relied on pragmatic diagnostic criteria reflecting real-world practice in resource-limited, high-burden settings. Viral or aseptic meningitis was diagnosed when a pathogen was identified on CSF PCR testing, acknowledging the limited availability of comprehensive viral panels. TBM was diagnosed in children presenting with focal neurological deficits such as hemiplegia and/or cranial nerve palsy in conjunction with supportive radiological or laboratory findings, with or without a documented TB contact history, given India’s high TB burden. Encephalitis was defined by the presence of fever and altered sensorium, with or without seizures, in the absence of an alternative diagnosis; characteristic magnetic resonance imaging findings, when available, were used to further support the diagnosis.

Serological assays are widely used for diagnosing arboviral and other systemic causes of AES. Common tests include plaque-reduction neutralization test (PRNT), haemagglutination inhibition test, indirect immunofluorescence assay, and ELISA (typically IgM/IgG). PRNT is the gold standard for distinguishing flavivirus cross-reactivity, while IgM ELISA is commonly used in clinical laboratories for rapid JE and dengue diagnosis. In our setting, JE IgM ELISA was available for selected patients, but PRNT and broad immunofluorescence assay panels were not routinely performed due to resource constraints; this limited definitive arboviral identification in several cases.

One of the most striking findings in this dataset is the changing profile of etiologies. Viral encephalitis emerged as the predominant cause of CNS infections, accounting for approximately 40% of the cases, whereas bacterial meningitis accounted for just over one-fourth. TBM remained stable, accounting for approximately 15% of the total burden. These findings align with national and international studies, which have shown a decline in bacterial meningitis incidence following the introduction of effective conjugate vaccines, as reported by Brouwer et al[14] and Kyaw et al[15].

The inclusion of the Hib vaccine in India’s Universal Immunization Programme in 2011, followed by the phased introduction of PCV-13 from 2017 onward, has been associated with a substantial decline in invasive bacterial diseases among Indian children, as demonstrated by Jayaraman et al[12] and Rajkumar et al[13]. Similar reductions in bacterial meningitis have been reported from multicenter surveillance networks across Asia and Africa by Oordt-Speets et al[16].

In contrast, viral encephalitis is increasingly recognized in routine hospital settings. Our study identified confirmed etiologies such as JE virus (JEV), herpes simplex virus, and enteroviruses, although a significant proportion of cases remained undifferentiated. This aligns with existing reports highlighting diagnostic challenges in LMICs, where the lack of molecular diagnostic facilities limits etiological confirmation, as noted by Easton and Solomon[17].

The rising proportion of viral encephalitis may reflect both ecological and diagnostic changes. Climatic shifts, extended monsoon seasons, and vector habitat expansion have enhanced arboviral transmission, particularly JEV. Improved awareness and adoption of PCR-based testing may also have contributed to increased recognition of viral causes. From a public-health perspective, this underscores the importance of sustaining JE vaccination, mosquito control, and early diagnostic access in rural hospitals.

The seasonal clustering of viral encephalitis cases during monsoon and post-monsoon months strongly supports the role of vector-borne arboviruses, particularly JEV, which is endemic in several Indian states. Other studies from Uttar Pradesh, Bihar, and Assam have also reported similar patterns, including Misra and Kalita[18] and Singh et al[19].

TBM, though less common in absolute numbers, contributed disproportionately to morbidity and mortality. The persistence of TBM as a stable etiological contributor reflects India’s high TB burden and highlights ongoing challenges in timely diagnosis, treatment initiation, and adherence, as described by Aulakh et al[20]. Despite the National TB Elimination Program’s renewed focus on pediatric TB, TBM outcomes remain poor, underscoring the urgent need for better diagnostics and integration of CNS-TB into national control strategies, as emphasized by Basu et al[21]. In countries like India, where the TB burden is high, early detection of TB and systematic contact tracing remain crucial strategies for reducing the incidence and severity of TBM in children. Early identification of exposed contacts and early initiation of anti-tubercular therapy can reduce progression to the severe category. In our study, the incidence of TBM remained relatively stable, with no significant year-to-year variation, suggesting the persistent burden of TB-related CNS infection despite ongoing national control programs. These findings highlight the continued need to strengthen TB surveillance in the pediatric age group, contact tracing, and early diagnostic pathways, particularly in rural and resource-limited settings.

The clinical features observed in our cohort were broadly consistent with established literature. Fever was nearly universal, while seizures and altered sensorium were prominent in viral encephalitis. Meningeal signs were seen in about one-third of cases, especially bacterial meningitis and TBM. Focal neurological deficits, although less frequent, were strongly predictive of adverse outcomes, as noted by Easton and Solomon[17].

A study by Goktug et al[22] suggested that Molecular diagnostics, such as multiplex CSF PCR panels, substantially increase etiological yield in meningitis/meningoencephalitis and have important implications for antimicrobial stewardship. Several studies report that CSF molecular results led to discontinuation of unnecessary antibiotics or antivirals in approximately one-third of cases, thereby shortening exposure to broad-spectrum therapy and guiding targeted treatment. In our cohort, routine molecular testing was limited; increased access to multiplex PCR at peripheral and tertiary centers could both improve pathogen detection and rationalize therapy in suspected CNS infections.

These findings reiterate the diagnostic complexity of pediatric CNS infections, as there is considerable clinical overlap between bacterial, viral, and tuberculous etiologies. In rural hospitals, where advanced neuroimaging or PCR-based assays are not readily available, clinicians often rely on clinical acumen supported by basic CSF analysis. The WHO case definitions for probable meningitis and AES remain valuable tools for surveillance and clinical decision-making in such contexts, as highlighted by WHO experts[23,24].

Despite a comprehensive evaluation, etiological confirmation was suboptimal. Only about one-third of bacterial meningitis cases were culture-positive, while less than half of viral encephalitis cases had virological confirmation. These limitations are consistent with other LMIC studies, such as those by Bumburidi et al[24] and Shen et al[25], where prior antibiotic exposure, limited laboratory sensitivity, and lack of advanced molecular panels reduce diagnostic yield.

An observation by Kumar et al[26], Neuroimaging abnormalities were noted in nearly 70% of children, proving to be valuable for clinical classification. Findings such as meningeal enhancement, cerebral edema, hydrocephalus, and ring-enhancing lesions were particularly useful for diagnosing TBM and brain abscesses. However, imaging facilities are not universally accessible in rural India, and referral delays can negatively affect outcomes.

Our study documented an overall mortality rate of 9.4%, with significant etiological differences. Mortality was highest in TBM (21.4%), followed by bacterial meningitis (11.4%), while viral encephalitis carried lower but non-negligible mortality (2.7%). These numbers are comparable to previous Indian and global studies, such as those by Attar et al[27], Afazel et al[28], which report mortality rates ranging between 5% and 15% for bacterial meningitis and up to 30% for TBM. The case-fatality rate observed in this study, particularly among children with TBM and bacterial meningitis, was comparable to rates reported in contemporary international series from tropical and resource-limited settings. Despite advances in antimicrobial therapy and supportive care, mortality associated with pediatric CNS infections remains substantial in such regions, reflecting delays in presentation, diagnostic limitations, and the severity of disease at admission.

The findings emphasize that an evidence-based, tiered diagnostic and treatment strategy can optimize resource use in rural settings. We recommend early clinical triage to identify high-risk children (age < 5 years, altered sensorium, seizures), prompt lumbar puncture where safe, concurrent initiation of empiric antibiotics (and antivirals when encephalitis is suspected), and targeted therapy once CSF culture/PCR or serology results are available. Wider availability of validated multiplex CSF PCR and rapid JE/dengue IgM testing can reduce unnecessary prolonged broad-spectrum antibiotic or antiviral exposure, allow earlier de-escalation, and shorten ICU stays; this both improves antimicrobial stewardship and conserves ICU and drug resources. For TBM, rapid molecular testing (e.g., GeneXpert) and early initiation of anti-tubercular therapy in suspected cases remain crucial to improve outcomes[14,28].

Neurological sequelae were observed in 18.3% of survivors. Post-infectious epilepsy emerged as the most frequent long-term complication, followed by motor deficits such as hemiparesis and cerebral palsy, as well as cognitive impairment. Such outcomes are consistent with global evidence, with Kvam et al[29] reporting that up to one in four survivors of pediatric bacterial meningitis or TBM sustain long-term disability. The psychosocial and economic burden of such sequelae is particularly pronounced in rural areas, where access to rehabilitation services such as physiotherapy, speech therapy, and neuropsychological support is limited, as highlighted by Kvam et al[29] and Nerkar et al[30]. Validated neurological screening questionnaires have demonstrated utility in detecting a broad spectrum of neurological impairments at the community level. Incorporating such tools into post-discharge follow-up programs may facilitate early identification of residual deficits and improve long-term outcomes, particularly in resource-limited rural settings.

The seasonal distribution of cases provides critical epidemiological insights. The clustering of encephalitis cases during the monsoon and post-monsoon months corresponds to vector abundance, flooding, and waterlogging conditions, which enhance arboviral transmission. Similar trends have been reported by Misra and Kalita[18] and Kakkar et al[31]. For hospitals in such regions, anticipating seasonal surges is essential for preparedness, including ensuring adequate bed strength, essential drugs, and trained staff.

Epileptiform activity on electroencephalography (EEG) in children is commonly attributable to CNS infections in endemic settings; several clinical series have identified CNS infection as the leading cause of new epileptiform discharges in children. This underscores the importance of infection-focused evaluation in children with new-onset seizures and abnormal EEGs[32]. Assessment of clinical, etiological, and EEG profiles aids in identifying infection-related epileptiform activity and guiding long-term management. Jagtap et al[33] reported that epileptiform EEG abnormalities were commonly associated with identifiable etiologies, particularly CNS infections, in children with seizures. These findings align with our observation of post-infectious epilepsy as a frequent sequela and support routine EEG assessment in children recovering from CNS infections.

Brain abscess etiology in children commonly follows contiguous spread from ear, mastoid, or paranasal sinus infections, hematogenous seeding from congenital cyanotic heart disease or systemic sepsis, or direct inoculation after trauma or neurosurgery. Typical pathogens include polymicrobial oral flora (anaerobes), Streptococcus species (including Streptococcus anginosus group), Staphylococcus aureus, and gram-negative bacilli. In our cohort (n = 5 brain abscesses), the majority followed contiguous otogenic infections.

Temporal trends during the four-year period showed a steady decline in bacterial meningitis cases (31% in 2021 to 21% in 2025), concurrent with a rise in viral encephalitis (34% in 2021 to 42% in 2025). TBM cases remained stable throughout. These opposing trajectories underscore the dynamic nature of CNS infection epidemiology and the need for continuous surveillance to guide preventive interventions.

Strengths and limitations

The major strength of this study lies in its relatively large sample size drawn over four years from a rural setting, an area often underrepresented in CNS infection research. The systematic evaluation of etiologies, seasonal patterns, and outcomes adds substantial epidemiological value.

Nonetheless, certain limitations must be acknowledged. Being retrospective, reliance on medical records may have introduced misclassification bias. Diagnostic confirmation in the present study was suboptimal, largely due to the limited availability and high cost of CSF PCR testing in a resource-constrained setting. Financial constraints restricted comprehensive virological evaluation in many cases, and although antigen detection tests were performed in selected patients, these often failed to identify a definitive pathogen. Long-term neurodevelopmental outcomes beyond discharge were not evaluated, restricting the assessment of true disability burden. Additionally, as a single-center study, caution is required in generalizing these findings to other rural populations. As a retrospective hospital-based study, long-term follow-up beyond discharge was unavailable, and a structured neurodevelopmental evaluation was not conducted. Consequently, the true burden of delayed or subtle sequelae may have been underestimated.

CONCLUSION

Pediatric CNS infections remain a significant cause of morbidity and mortality in rural western India. Strengthening vaccination programs (Hib, PCV-13, and JE), improving early referral and molecular diagnostic capacity, and integrating rehabilitation services can meaningfully improve outcomes. Future prospective multicentric studies should assess long-term neurodevelopmental sequelae to guide rural healthcare policy.