Acute febrile illness (AFI) in children—typically fever of sudden onset lasting up to 14 days—remains a dominant reason for pediatric outpatient attendance, emergency evaluation, and hospitalization in low- and middle-income countries.^1,2 The diagnostic challenge arises from the non-specific nature of early symptoms and the substantial overlap between viral, bacterial, and parasitic infections.^1–3 In tropical settings, dengue, malaria, enteric fever, scrub typhus, leptospirosis, and viral respiratory infections frequently coexist and may present with similar clinical patterns such as fever with myalgia, vomiting, headache, rash, and variable organ dysfunction.^2,4,5 Seasonal clustering further complicates decision-making because multiple pathogens surge simultaneously during and after monsoon months.^6 A significant proportion of children with AFI remain “undifferentiated” at first contact even after initial evaluation, delaying targeted therapy and increasing reliance on empirical antimicrobials.^1,7 This contributes to avoidable antimicrobial exposure and may miss time-sensitive infections (for example, severe dengue, complicated malaria, or scrub typhus with evolving organ failure) where early supportive care and disease-specific treatment alter outcomes.^5,8,9 For dengue, warning signs such as abdominal pain, persistent vomiting, mucosal bleeding, lethargy, hepatomegaly, and rising hematocrit with falling platelets indicate risk of progression to severe disease and need close monitoring or admission.^10,11 Similarly, scrub typhus—an increasingly recognized cause of pediatric AFI—may present without a visible eschar; thrombocytopenia, transaminitis, hypoalbuminemia, shock, and altered sensorium are markers of severe disease and poorer outcomes.^8,12 Because laboratory confirmation for every possible etiology is impractical, many guidelines advocate a structured syndromic approach: identify danger signs, evaluate for common treatable causes using point-of-care tests (e.g., malaria rapid test, dengue NS1/IgM), and tailor further testing based on clinical phenotype (respiratory focus, urinary symptoms, jaundice, CNS features, or bleeding tendency).^2,10,11 However, etiologic patterns and outcome predictors vary by geography, referral pathways, and local outbreaks.^4,6,8 Therefore, institution-based clinical profiling remains valuable for clinicians to refine local diagnostic algorithms, guide rational investigations, and anticipate complications. This study aimed to describe the clinical profile, etiologic spectrum, management patterns, and outcomes among children presenting with AFI to a tertiary-care hospital, and to identify clinical and laboratory predictors of severe outcomes (ICU admission and/or death).

Prospective observational study conducted in the Department of Pediatrics of a tertiary-care teaching hospital over 12 months. Study population Children aged 1 month to 12 years presenting with fever ≤14 days were screened in the emergency room and pediatric wards. Inclusion criteria 1. Documented fever (axillary/tympanic/rectal) ≥38.0°C or history of fever within the preceding 48 hours. 2. Fever duration ≤14 days. 3. No confirmed etiologic diagnosis at the time of triage (i.e., acute undifferentiated febrile illness or AFI pending work-up). 4. Parent/guardian consent. Exclusion criteria 1. Fever >14 days (evaluation aligned more with FUO work-up). 2. Known chronic conditions likely to confound presentation/outcomes: malignancy, primary immunodeficiency, chronic kidney disease, chronic liver disease, congenital heart disease with heart failure, long-term steroid/immunosuppressant therapy. 3. Proven non-infectious inflammatory disease at presentation (e.g., confirmed systemic JIA, SLE flare). 4. Hospitalization within the last 14 days for another acute illness. 5. Neonates <28 days (separate sepsis pathway). Clinical evaluation and investigations A standardized proforma captured demographics, nutritional status, vitals, and danger signs (shock, respiratory distress, altered sensorium, seizures, active bleeding). Baseline investigations included CBC with platelet count, hematocrit, random blood glucose, CRP (as per clinician discretion), liver function tests (AST/ALT, bilirubin), renal function tests (urea/creatinine), electrolytes, and urinalysis. Etiology-directed tests were ordered using a syndromic protocol: • Dengue: NS1 antigen and/or IgM/IgG based on day of illness. • Malaria: peripheral smear and/or rapid antigen test. • Scrub typhus: IgM ELISA when clinically suspected (hepatosplenomegaly, lymphadenopathy, thrombocytopenia, transaminitis, eschar, or non-response to beta-lactams). • Enteric fever: blood culture (preferred) and/or IgM rapid test where culture unavailable. • UTI: urine culture for pyuria/positive nitrite. • Lower respiratory infection: chest radiograph when indicated. Treatment and outcomes All children received supportive care. Antimicrobials/antimalarials were administered when clinically indicated. Primary outcomes were length of stay, ICU admission, shock requiring vasoactive support, need for ventilation, and in-hospital mortality. Severe outcome was defined as ICU admission and/or death. Statistical analysis Categorical variables were summarized as n (%), continuous variables as mean ± SD or median (IQR). Chi-square/Fisher’s exact tests compared proportions. Variables with p<0.10 on univariate analysis were entered into logistic regression to identify independent predictors of severe outcome; p<0.05 was considered significant.

Table 1. Baseline characteristics (N=240) Variable Value Age (years), mean ± SD 5.1 ± 3.2 Age group: <1 year 32 (13.3%) 1–5 years 98 (40.8%) 6–12 years 110 (45.8%) Male 138 (57.5%) Rural residence 146 (60.8%) Fever duration before presentation (days), median (IQR) 4 (3–6) Moderate/severe acute malnutrition 34 (14.2%) AFI predominantly affected preschool and school-aged children, with mild male predominance. Median fever duration suggested presentation around the “decision point” when warning signs often emerge in dengue and scrub typhus.^10,12 Table 2. Clinical features at presentation Feature n (%) Vomiting 96 (40.0) Cough/coryza 84 (35.0) Abdominal pain 62 (25.8) Headache/myalgia (age-appropriate) 58 (24.2) Rash 38 (15.8) Diarrhea 36 (15.0) Bleeding manifestations 18 (7.5) Altered sensorium/seizures 20 (8.3) Hepatomegaly 54 (22.5) Splenomegaly 42 (17.5) Lymphadenopathy 30 (12.5) Eschar 10 (4.2) Shock at arrival 22 (9.2) Gastrointestinal symptoms and respiratory symptoms were common, but a clinically important minority had shock/neurologic involvement—key markers of severe disease across dengue, malaria, sepsis, and rickettsial illness.^8,10,11 A treatable pathogen was identified in most children, with dengue leading. The low but present “undiagnosed” fraction is consistent with AFI literature where even with testing, a proportion remains without definitive etiology.^1,7 Table 3. Laboratory profile Parameter Finding (n, %) / Mean ± SD Hemoglobin (g/dL), mean ± SD 10.8 ± 1.6 Leukocytosis (>15,000/mm³) 52 (21.7%) Leukopenia (<4,000/mm³) 28 (11.7%) Thrombocytopenia (<150,000/mm³) 104 (43.3%) Severe thrombocytopenia (<50,000/mm³) 26 (10.8%) Hematocrit elevated (age-adjusted) 44 (18.3%) AST or ALT >2× ULN 78 (32.5%) Creatinine elevated (AKI as per age norms) 20 (8.3%) CRP elevated (>10 mg/L)* 88/190 (46.3%) *CRP performed when clinician suspected bacterial infection/sepsis. Thrombocytopenia and transaminitis were frequent—supporting dengue and scrub typhus as major contributors locally and highlighting the utility of CBC + LFT as early risk screens.^8,10,12 Table 4. Etiologic diagnosis Etiology n (%) Dengue (NS1/IgM positive) 64 (26.7) Enteric fever (culture/IgM supportive) 42 (17.5) Malaria (smear/RDT positive) 28 (11.7) Scrub typhus (IgM ELISA positive) 24 (10.0) Pneumonia (clinical + radiologic) 18 (7.5) UTI (culture positive) 8 (3.3) Viral URTI/viral fever (clinical) 40 (16.7) No etiology identified 16 (6.7) Table 5. Management and outcomes Outcome/Intervention n (%) / Value Received antibiotics 132 (55.0) Received antimalarial therapy 28 (11.7) Received doxycycline/azithromycin for suspected rickettsial illness 30 (12.5) IV fluids (bolus/resuscitation) 68 (28.3) Platelet transfusion 14 (5.8) ICU admission 28 (11.7) Ventilatory support 10 (4.2) Length of stay (days), median (IQR) 4 (3–6) Discharged improved 236 (98.3) Death 4 (1.7) Most children recovered with supportive care and targeted therapy. ICU need (~12%) underscores the importance of early danger-sign recognition and step-up monitoring pathways in AFI seasons.^10,11 Table 6. Predictors of severe outcome (ICU admission/death) (N=240) Variable Severe outcome n/N (%) Adjusted OR (95% CI) p-value Shock at presentation 16/22 (72.7) 9.8 (4.0–24.2) <0.001 Altered sensorium/seizures 12/20 (60.0) 5.1 (2.0–13.0) 0.001 Platelets <50,000/mm³ 14/26 (53.8) 3.6 (1.5–8.7) 0.005 AST/ALT >2× ULN 18/78 (23.1) 2.4 (1.1–5.0) 0.02 AKI (creatinine elevated) 10/20 (50.0) 3.9 (1.5–10.2) 0.006 Hemodynamic instability, neurologic involvement, severe thrombocytopenia, hepatic injury, and AKI independently predicted severe outcomes—consistent with severe dengue, complicated malaria, septic shock, and severe scrub typhus phenotypes.^8,10,12

This study describes the spectrum of AFI in children in a tertiary-care setting, demonstrating that dengue, enteric fever, malaria, and scrub typhus collectively accounted for a substantial proportion of identified etiologies. Similar hospital-based AFI studies in tropical regions report dengue and rickettsial infections as important drivers of pediatric admissions, especially during monsoon and post-monsoon months.^1,4,5 Scrub typhus, once considered geographically restricted, is increasingly recognized as a major cause of undifferentiated fever in India, frequently presenting without eschar and mimicking dengue or enteric fever.^8,12 In our cohort, eschar was uncommon, aligning with published pediatric scrub typhus series where eschar prevalence varies widely and absence does not exclude disease.^8,12,13 Clinically, gastrointestinal symptoms (vomiting, abdominal pain) and systemic signs (hepatosplenomegaly, lymphadenopathy) were frequent, reflecting the overlap between dengue and rickettsial disease.^10,12 The observed laboratory pattern—thrombocytopenia and transaminitis—also mirrors prior pediatric data in dengue and scrub typhus.^10,12,14 Importantly, severe thrombocytopenia (<50,000/mm³) independently predicted severe outcomes in our analysis, supporting its role as a pragmatic triage marker when combined with warning signs. National dengue guidance emphasizes admission and close monitoring when warning signs or evolving hemoconcentration with thrombocytopenia occurs, which is consistent with our finding that shock and organ dysfunction were dominant predictors of ICU care.^11 The proportion of children requiring ICU support (11.7%) and the low mortality (1.7%) suggest that early resuscitation, timely escalation, and targeted antimicrobials can yield favorable outcomes even in mixed-etiology AFI settings. Predictors of severe outcomes in our study—shock, altered sensorium, hepatic injury, and AKI—are also highlighted in severe scrub typhus cohorts and broader pediatric sepsis literature, where organ dysfunction at presentation correlates strongly with mortality and prolonged hospitalization.^12,15,16 These findings reinforce that AFI management should not focus solely on “naming the pathogen,” but equally on early identification of physiologic derangement and organ involvement. A syndromic approach is therefore practical: (i) screen for danger signs and treat shock promptly, (ii) run a minimal high-yield panel (CBC with hematocrit/platelets, LFT, creatinine), (iii) apply focused rapid tests/serology for dengue and malaria early, and (iv) maintain a low threshold for rickettsial testing/empiric therapy in appropriate clinical contexts, particularly when thrombocytopenia and transaminitis coexist or fever persists beyond 5 days.^8,11,12 Limitations: Single-center design may limit generalizability; not all children underwent uniform testing (e.g., CRP), and some “viral fever” diagnoses were clinical without PCR confirmation. Nevertheless, the study reflects real-world decision-making and provides locally useful predictors for early risk stratification.

AFI in children shows diverse etiologies with considerable clinical overlap. Dengue, enteric fever, malaria, and scrub typhus were leading causes in this cohort. Shock, altered sensorium, severe thrombocytopenia, transaminitis, and AKI predicted severe outcomes. A danger-sign–based triage combined with focused testing and timely escalation can improve outcomes and reduce missed severe disease.

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