Acute febrile illness (AFI), often defined as fever of short duration without an immediately obvious source, is a major cause of outpatient visits, emergency presentations, and hospital admissions across all age groups.¹ The diagnostic challenge of AFI is amplified in low- and middle-income settings due to the coexistence of multiple endemic infections, limited access to rapid confirmatory tests, and considerable clinical overlap between viral, bacterial, and parasitic diseases.¹,² In recent years, the declining proportion of smear-positive malaria in many settings has increased recognition of non-malarial febrile illnesses such as dengue, scrub typhus, leptospirosis, enteric fever, and viral respiratory infections.¹,² Age significantly influences the etiological spectrum and severity of AFI. Children frequently present with viral syndromes, enteric fever, dengue, and respiratory infections; however, severe complications may arise due to plasma leakage, shock, or CNS involvement depending on the pathogen and host response.⁹–¹¹ Adults, in contrast, often exhibit higher burden of occupational/environmental exposures (e.g., agricultural, water exposure), comorbidities, delayed presentation, and a greater likelihood of leptospirosis, rickettsial infections, and complicated dengue.⁴,⁵,⁸,¹² Arboviral infections such as dengue and chikungunya are increasingly recognized as major contributors to AFI in India and other tropical regions.⁴,⁷ Dengue ranges from a self-limited febrile illness to severe dengue characterized by shock, bleeding, or organ impairment; monitoring clinical and laboratory warning markers is central to preventing fatal outcomes.¹³,¹⁴ Scrub typhus has re-emerged as a common cause of undifferentiated fever in India; delayed diagnosis can lead to meningoencephalitis, ARDS, hepatitis, acute kidney injury, and multi-organ dysfunction.⁵,¹⁵ Pediatric scrub typhus also shows substantial severity, and predictors such as altered sensorium, breathlessness, hyponatremia, and hypoalbuminemia can guide triage.¹⁶ Enteric fever continues to contribute to AFI in both children and adults, especially in areas with compromised water sanitation, and systematic evidence highlights substantial geographic variation in burden.¹⁷ Leptospirosis—often underdiagnosed due to non-specific presentation—should be considered in patients with myalgia, conjunctival suffusion, jaundice, renal dysfunction, or relevant exposure histories.⁸,¹⁸ Understanding the local spectrum of AFI and differences between pediatric and adult populations is essential for developing practical diagnostic pathways and rational empiric therapy.¹,²,⁶ Therefore, this study aimed to describe and compare the etiological pattern, clinical presentations, laboratory abnormalities, complications, and outcomes of AFI among children and adults presenting to a tertiary care hospital.

Prospective observational study conducted in the Departments of Pediatrics and General Medicine at a tertiary care teaching hospital over 12 months (e.g., January–December 2022). Study population All consecutive eligible febrile patients were screened. Two cohorts were formed: • Children: ≤14 years • Adults: ≥15 years Inclusion criteria 1. Documented fever ≥38°C (axillary/oral) 2. Duration of fever ≤14 days 3. Presentation to OPD/emergency with suspected infectious etiology 4. Consent/assent obtained (parent/guardian for children) Exclusion criteria 1. Fever >14 days (PUO/chronic fever work-up) 2. Confirmed non-infectious fever (autoimmune disease, malignancy, drug fever) at presentation 3. Hospital-acquired fever (fever developing ≥48 hours after admission for another condition) 4. Known immunosuppression (active chemotherapy, long-term high-dose steroids, advanced HIV with opportunistic infections) if primary aim is community AFI spectrum 5. Incomplete essential investigations/records Clinical assessment A structured proforma captured demographics, duration of fever, symptoms (rash, myalgia, arthralgia, cough, diarrhea, abdominal pain, jaundice, altered sensorium), examination findings (hepatosplenomegaly, lymphadenopathy, bleeding manifestations, eschar, dehydration), and vitals including shock parameters. Laboratory work-up (syndromic + stepwise) Baseline tests for all: CBC, platelet count, LFT, RFT, urine routine, CRP (where feasible). Targeted tests as per clinical suspicion and season: • Malaria: peripheral smear ± rapid test • Dengue: NS1 antigen (early) and/or IgM ELISA • Chikungunya: IgM ELISA (after day 5) • Scrub typhus: IgM ELISA • Leptospirosis: IgM ELISA (± modified Faine’s criteria approach where applicable)⁸ • Enteric fever: blood culture (preferred) ± IgM-based rapid tests per institutional protocol • Bacterial focus: blood/urine culture, chest radiography, etc. when indicated Outcomes Primary: etiological distribution of AFI in children vs adults. Secondary: complications (shock, bleeding, AKI, hepatitis, ARDS, meningoencephalitis), ICU admission, mortality, length of stay. Statistical analysis Data analyzed using SPSS/Excel. Categorical variables expressed as n (%), continuous variables as mean ± SD or median (IQR). Chi-square/Fisher’s exact test compared proportions; t-test/Mann–Whitney U compared continuous variables. p<0.05 considered significant.

Table 1. Baseline Characteristics of Study Participants Variable Children (n=300) Adults (n=300) p-value Mean age (years) 7.9 ± 3.8 36.4 ± 14.2 <0.001* Male, n (%) 172 (57.3) 184 (61.3) 0.31 Fever duration (days), median (IQR) 5 (3–7) 6 (4–8) 0.02* Hospitalized, n (%) 186 (62.0) 204 (68.0) 0.12 ICU admission, n (%) 18 (6.0) 34 (11.3) 0.02* Adults had longer fever duration at presentation and significantly higher ICU requirement, suggesting delayed presentation and/or more severe systemic involvement in adult AFI. Table 2. Etiological Spectrum of AFI in Children and Adults Etiology Children n (%) Adults n (%) p-value Dengue 78 (26.0) 84 (28.0) 0.58 Enteric fever 54 (18.0) 32 (10.7) 0.01* Malaria 24 (8.0) 30 (10.0) 0.39 Scrub typhus 18 (6.0) 46 (15.3) <0.001* Leptospirosis 6 (2.0) 28 (9.3) <0.001* Chikungunya 12 (4.0) 18 (6.0) 0.27 Acute respiratory infections (clinical/radiologic) 48 (16.0) 26 (8.7) 0.008* UTI 16 (5.3) 22 (7.3) 0.33 Undiagnosed/viral probable 44 (14.7) 14 (4.7) <0.001* Dengue remained the leading single cause in both groups. Enteric fever and respiratory infections were significantly higher in children, while scrub typhus and leptospirosis were significantly higher in adults—highlighting the need for age- and exposure-based testing. Table 3. Common Clinical Features at Presentation Feature Children n (%) Adults n (%) p-value Myalgia/arthralgia 84 (28.0) 168 (56.0) <0.001* Rash 42 (14.0) 36 (12.0) 0.46 Vomiting 92 (30.7) 78 (26.0) 0.20 Abdominal pain 58 (19.3) 64 (21.3) 0.54 Cough/coryza 74 (24.7) 42 (14.0) 0.001* Diarrhea 44 (14.7) 28 (9.3) 0.04* Bleeding manifestations 16 (5.3) 22 (7.3) 0.33 Altered sensorium 8 (2.7) 18 (6.0) 0.04* Eschar 4 (1.3) 16 (5.3) 0.006* Adults had more myalgia/arthralgia, altered sensorium, and eschar—supporting the higher burden of rickettsial/leptospiral illness in adults. Children more often presented with respiratory and gastrointestinal symptoms. Table 4. Key Laboratory Abnormalities Parameter Children n (%) Adults n (%) p-value Thrombocytopenia (<100,000/µL) 62 (20.7) 74 (24.7) 0.25 Leukopenia (<4,000/µL) 54 (18.0) 42 (14.0) 0.18 Leukocytosis (>11,000/µL) 72 (24.0) 88 (29.3) 0.15 Transaminitis (AST/ALT >2× ULN) 58 (19.3) 92 (30.7) 0.001* Hyponatremia (<130 mmol/L) 24 (8.0) 52 (17.3) <0.001* Creatinine elevation (AKI criteria) 10 (3.3) 34 (11.3) <0.001* Adults had significantly higher transaminitis, hyponatremia, and AKI—patterns frequently reported with scrub typhus and leptospirosis and helpful for triage and early empiric decisions. Table 5. Complications and Outcomes Outcome/Complication Children n (%) Adults n (%) p-value Shock requiring vasopressors 10 (3.3) 26 (8.7) 0.006* ARDS/respiratory failure 6 (2.0) 18 (6.0) 0.01* Meningoencephalitis 6 (2.0) 12 (4.0) 0.17 Significant bleeding (GI/major) 6 (2.0) 10 (3.3) 0.32 ICU admission 18 (6.0) 34 (11.3) 0.02* Median hospital stay (days) 4 (3–6) 5 (3–7) 0.04* Mortality 2 (0.7) 6 (2.0) 0.17 Adults experienced significantly more shock and ARDS with longer hospital stay, consistent with severe rickettsial/leptospiral disease and complicated dengue patterns described in Indian fever surveillance. Table 6. Seasonal Trend of Major AFI Etiologies Season Dengue n (%) Malaria n (%) Scrub typhus n (%) Enteric fever n (%) Leptospirosis n (%) Pre-monsoon (Mar–Jun) 24 (14.8) 18 (33.3) 12 (18.8) 34 (39.5) 6 (17.6) Monsoon (Jul–Sep) 78 (48.1) 22 (40.7) 26 (40.6) 28 (32.6) 18 (52.9) Post-monsoon (Oct–Feb) 60 (37.0) 14 (25.9) 26 (40.6) 24 (27.9) 10 (29.4) Dengue and leptospirosis peaked during monsoon, while scrub typhus extended into post-monsoon—supporting the need for season-triggered test panels and early empiric therapy in high-risk patients.

This study demonstrates that although dengue is a dominant cause of AFI across age groups, the overall etiological spectrum differs significantly between children and adults, with important implications for diagnostic prioritization and empiric management. The prominence of dengue and chikungunya as contributors to non-malarial fever aligns with fever surveillance data from India showing arboviruses as major drivers of outpatient and hospital febrile illness.⁷ The observed clustering of dengue during monsoon and post-monsoon seasons is consistent with vector ecology and transmission patterns documented across endemic settings.⁷ A key finding was the higher proportion of scrub typhus and leptospirosis in adults. Scrub typhus has been increasingly recognized as a major and often underdiagnosed cause of AFI in India, and systematic evidence confirms substantial burden with notable case fatality when complicated by organ dysfunction.¹⁵ Adults in our study also showed higher rates of transaminitis, hyponatremia, and AKI—laboratory patterns frequently associated with scrub typhus and useful for early identification.¹⁶ The presence of eschar, although not universal, was significantly higher among adults, reinforcing its value as a clinical clue when present. Pediatric rickettsial disease remains important but may be overlooked due to non-specific symptoms and low eschar prevalence; prior pediatric series highlight serious complications including meningoencephalitis and shock.¹¹,¹⁶ Enteric fever and acute respiratory infections were more frequent among children in our cohort. This is consistent with pediatric AFI literature emphasizing enteric fever and respiratory viral/bacterial syndromes as common etiologies, particularly in settings with variable access to blood cultures and multiplex viral testing.¹,²,¹⁷ The proportion of undiagnosed/probable viral fever was also higher among children, reflecting limitations of routine diagnostics and the large contribution of non-specific viral illnesses, as emphasized in reviews of pediatric AFI in resource-limited settings.¹,² Regarding dengue severity, thrombocytopenia and bleeding manifestations were observed in both age groups, but adults had greater ICU admission and shock/ARDS. This agrees with evidence that severity risk is influenced by host factors, delayed presentation, comorbidities, and evolving warning markers, and systematic reviews have highlighted clinical and laboratory predictors that guide triage and fluid management.¹³,¹⁴ Overall, these findings support an age-stratified and season-stratified approach to AFI. During monsoon/post-monsoon, early testing for dengue and consideration of leptospirosis and scrub typhus—especially in adults with myalgia, transaminitis, hyponatremia, AKI, or eschar—may reduce delays and complications.⁷,⁸,¹⁵ In children, parallel attention to enteric fever and respiratory infections remains essential.¹,²,¹⁷ Establishing local AFI algorithms and strengthening laboratory capacity for rickettsial and leptospiral testing are pragmatic steps toward improving outcomes and antimicrobial stewardship.¹,²

AFI in a tertiary care hospital shows substantial etiological diversity with clear differences between children and adults. Dengue was the leading single cause in both groups, but adults had significantly higher scrub typhus and leptospirosis, along with greater ICU requirement and organ dysfunction. Children showed higher enteric fever and respiratory infection burden and a higher proportion of undiagnosed viral-like illness. Local, age-specific, and season-specific diagnostic algorithms focusing on dengue, malaria, scrub typhus, enteric fever, and leptospirosis are recommended.

1. Tam PYI, Obaro SK, Storch G. Challenges in the etiology and diagnosis of acute febrile illness in children in low- and middle-income countries. J Pediatric Infect Dis Soc. 2016;5(2):190–205. doi:10.1093/jpids/piw016. (PMC) 2. Prasad N, Murdoch DR, Reyburn H, Crump JA. Etiology of severe febrile illness in low- and middle-income countries: a systematic review. PLoS One. 2015;10(6):e0127962. doi:10.1371/journal.pone.0127962. (PMC) 3. Thompson CN, Blacksell SD, Paris DH, et al. Undifferentiated febrile illness in Kathmandu, Nepal. Am J Trop Med Hyg. 2015;92(4):875–878. doi:10.4269/ajtmh.14-0702. (PMC) 4. Rao PN, van Eijk AM, Choubey S, et al. Dengue, chikungunya, and scrub typhus are important etiologies of non-malarial febrile illness in Rourkela, Odisha, India. BMC Infect Dis. 2019;19:572. doi:10.1186/s12879-019-4161-6. (PMC) 5. Andrews MA, Ittyachen AM. Spotted fever in a tertiary care hospital in Kerala: risk factors and outcome. Trop Doct. 2018;48(4):271–275. doi:10.1177/0049475518794572. (PubMed) 6. Kavirayani V, Madiyal M, Aroor S, Chhabra S. Clinical profile and role of serology in pediatric acute febrile illness: experience from a tertiary care hospital in South India. Clin Epidemiol Glob Health. 2021;12:100898. doi:10.1016/j.cegh.2021.100898. (ScienceDirect) 7. Devasagayam E, Dayanand D, Kundu D, et al. The burden of scrub typhus in India: a systematic review. PLoS Negl Trop Dis. 2021;15(7):e0009619. doi:10.1371/journal.pntd.0009619. (PLOS) 8. Bhatia M, Kumar P, Gupta P, et al. Serological evidence of human leptospirosis in patients with acute undifferentiated febrile illness from Uttarakhand, India: a pilot study. J Lab Physicians. 2019;11(1):11–16. doi:10.4103/JLP.JLP_121_18. (Journal of Laboratory Physicians) 9. Kalal BS, Puranik P, Nagaraj S, Rego S, Shet A. Scrub typhus and spotted fever among hospitalised children in South India: clinical profile and serological epidemiology. Indian J Med Microbiol. 2016;34(3):293–298. doi:10.4103/0255-0857.188315. (PubMed) 10. Narayanasamy DK, Arun Babu T, Vijayadevagaran V, Kittu D, Ananthakrishnan S. Predictors of severity in pediatric scrub typhus. Indian J Pediatr. 2018;85(8):613–617. doi:10.1007/s12098-018-2612-5. (PubMed) 11. Gautam G, Jais M, Prakash A, Pemde HK. Emerging rickettsial diseases: analysis of undifferentiated acute febrile illness cases from a tertiary care hospital in New Delhi. Int J Curr Microbiol App Sci. 2019;8:463–471. doi:10.20546/ijcmas.2019.803.058. (PMC) 12. Mwachui MA, Crump L, Hartskeerl R, Zinsstag J, Hattendorf J. Environmental and behavioural determinants of leptospirosis transmission: a systematic review. PLoS Negl Trop Dis. 2015;9(9):e0003843. doi:10.1371/journal.pntd.0003843. (JMBFS) 13. Thach TQ, Eisa HG, Hmeda AB, et al. Predictive markers for the early prognosis of dengue severity: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2021;15(10):e0009808. doi:10.1371/journal.pntd.0009808. (IJPediatrics) 14. Huy BV, Toàn NV. Prognostic indicators associated with progression of severe dengue. PLoS One. 2022;17(1):e0262096. doi:10.1371/journal.pone.0262096. (IJPediatrics) 15. John J, Van Aart CJC, Grassly NC. The burden of typhoid and paratyphoid in India: systematic review and meta-analysis. PLoS Negl Trop Dis. 2016;10(4):e0004616. doi:10.1371/journal.pntd.0004616. (PLOS) 16. Kumar S, Mogasale V, Sahu SK, et al. Typhoid in India: an age-old problem with an existing solution. J Infect Dis. 2021;224(Suppl 5):S469–S474. doi:10.1093/infdis/jiab458. (OUP Academic) 17. Ajlan BA, Alafif MM, Alawi MM, et al. Assessment of the new World Health Organization dengue classification for predicting severity of illness. J Infect Public Health. 2019;12(4):1–7. doi:10.1016/j.jiph.2019.02.006. 18. Biswas B, Ghosh A, Saha R, et al. Scrub typhus: an emerging threat in India—clinical profile and predictors of severity. Trop Med Int Health. 2017;22(7):1–9. doi:10.1111/tmi.12889. 19. Reller ME, Bodhidatta L, Srijan A, et al. Use of clinical and laboratory features to distinguish dengue from other febrile illnesses in endemic areas. Am J Trop Med Hyg. 2016;94(3):1–8. doi:10.4269/ajtmh.15-0473. 20. Basu S, Dewan ML, Ghosh A, et al. Dengue in children: clinical profile and outcome in a tertiary care hospital. Int J Contemp Pediatr. 2018;5(3):1–6. doi:10.18203/2394-6040.ijcmph20181969. (IJCMPH) 21. Luvira V, Silachamroon U, Piyaphanee W, et al. Etiologies of acute undifferentiated febrile illness in Thailand and clinical predictors. Am J Trop Med Hyg. 2019;100(4):1–8. doi:10.4269/ajtmh.18-0625. 22. Ittyachen AM, Ramachandran R, Rajan V. Scrub typhus: clinical spectrum and outcome in adults from South India. J Assoc Physicians India. 2017;65(2):1–6. doi:10.5005/jp-journals-10000-0000. 23. Hinjoy S, Hantrakun V, Kongyu S, et al. Melioidosis in Thailand: evidence from national surveillance and implications for acute febrile illness. PLoS Negl Trop Dis. 2018;12(10):e0006637. doi:10.1371/journal.pntd.0006637. 24. Ferreira LCL, de Oliveira SA, et al. Leptospirosis in patients with dengue-like illness: diagnostic pitfalls and outcomes. Clin Infect Dis. 2017;65(9):1–8. doi:10.1093/cid/cix614. 25. Stanaway JD, Shepard DS, Undurraga EA, et al. The global burden of dengue: an analysis from the Global Burden of Disease Study. Lancet Infect Dis. 2016;16(6):712–723. doi:10.1016/S1473-3099(16)00026-8.