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Abstract

A 12-year-old boy, the eldest child of a non-consanguineous couple from a lower socio-economic background, was brought with a history of fever for four days, headache for five days, and four episodes of vomiting associated with giddiness over the last three days. His immunizations were up to date, and his developmental milestones were normal. There was no relevant antenatal, perinatal, or past medical history. He was initially managed at Haveri District Hospital and later referred to Karnataka Medical College and Research Institute for further evaluation. Family history was unremarkable, and his nutritional intake was reported to be adequate. On admission, his vital parameters were stable. General examination showed no gross abnormalities, though anthropometry suggested undernutrition. Neurological assessment revealed meningeal signs, including neck stiffness, positive Kernig’s sign, and positive Brudzinski’s sign. Other systemic examinations were within normal limits. Laboratory investigations demonstrated leukocytosis on complete blood count, while renal and liver function tests and serum electrolytes were normal. Cerebrospinal fluid analysis showed lymphocytic predominance, and confirmatory testing established the diagnosis of Japanese Encephalitis.

Keywords

Japanese Encephalitis, Acute Febrile Encephalopathy, Pediatric Neurology, Meningeal Signs, Cerebrospinal Fluid Analysis

Introduction

Japanese encephalitis (JE) continues to pose a major health challenge across Asia [1]. The disease is caused by the Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that has been recognized as the leading cause of viral encephalitis in the region [2,3]. Historical records show that outbreaks were noted as early as the late 19th century in Japan, and in 1935, the Nakayama strain of JEV was first isolated from a fatal case, later becoming the standard reference strain [4]. JEV belongs to the Flavivirus genus, which also includes important human pathogens such as dengue, yellow fever, Murray Valley encephalitis, West Nile virus, Zika virus, St. Louis encephalitis, and tick-borne encephalitis viruses [5,13].

Globally, JE is responsible for a significant burden of illness and mortality. WHO has estimated that tens of thousands of cases occur each year, with mortality rates ranging between 20–30%. In 2015, the number of reported cases exceeded 100,000, with up to 30,000 deaths [6]. Children under 15 years of age remain the most vulnerable group, particularly newborns and young children, who are more likely to develop severe neurological complications [7]. Clinical presentation often includes fever, headache, muscle pain, and altered mental status, with seizures observed in the majority of patients [14].

As there is no antiviral treatment specifically for JE, vaccination remains the cornerstone of prevention and control [8]. The most widely used vaccines are based on JEV genotype III and have been deployed across endemic areas with proven effectiveness [9]. However, surveillance data suggest that the true burden of disease is underestimated due to misdiagnosis, a problem common to several rare neurological and metabolic disorders [11]. At present, it is estimated that more than two billion people live in areas at risk of JEV transmission, and increasing mosquito populations may further expand its geographic range.

Transmission occurs primarily through the bite of infected female Culex tritaeniorhynchus mosquitoes [10]. The main amplifying hosts are pigs and certain bird species, particularly herons and egrets from the Ardeidae family [12].

Case report

Demographic details and chief complaints

A 12-year-old male child, the first-born of a non-consanguineously married couple, presented to the Karnataka Medical College and Research Institution (KMCRI), Hubballi, and was admitted on 15th February 2024 with the following chief complaints:

  • Headache for the past 5 days
  • Multiple episodes of vomiting for the past 5 days
  • Fever for the past 4 days
  • Giddiness and imbalance for the past 3 days

The child was apparently well until 5 days prior to admission, when he developed a diffuse, continuous headache of moderate to severe intensity. The headache was not relieved by over-the-counter analgesics and progressively worsened over the following days. It was associated with nausea and multiple episodes of non-projectile, non-bilious vomiting, occurring 3–4 times per day.

A low-grade intermittent fever developed on the fourth day of illness, without chills or rigors. It was not associated with rash, seizures, or altered sensorium. The child also began to complain of giddiness, described as a feeling of light-headedness and imbalance while walking, leading to general discomfort and reduced physical activity.

There was no history of trauma, visual disturbances, ear discharge, neck stiffness, loss of consciousness, or any recent travel. There is no known history of tuberculosis exposure, and no significant past medical or surgical history. Immunizations are up to date for age.

Family history is non-contributory, and there is no known consanguinity between the parents.

Past History:

Prior to admission at KMCRI, the child was evaluated and admitted at a district hospital in Haveri for the same complaints—headache, vomiting, fever, and giddiness. Due to persistent symptoms and lack of significant clinical improvement, he was referred to Karnataka Medical College and Research Institution, Hubballi, for further evaluation and management.

Past Medical History:

During his stay at the district hospital, the child was treated empirically for a suspected infection. The following medications were administered:

  • Inj. Ceftriaxone 1.2 g BD (intravenously)
  • Inj. Amikacin 150 mg OD (intravenously)

A CT scan of the brain was performed, which was reported as normal, ruling out gross structural abnormalities, intracranial hemorrhage, or space-occupying lesions at that point.

There is no prior history of chronic illness, hospitalization, neurological disorders, or known drug allergies. Growth and developmental milestones have been age-appropriate.

Family history

Figure:1

The patient is the first-born child of a non-consanguineously married couple. The family consists of two male children—the patient, aged 12 years, and a younger sibling aged 6 years. The second child, an 11-year-old male, is reported to be in good health with no significant medical history. There is no known history of hereditary or genetic disorders, neurological illnesses, or chronic diseases in the immediate or extended family.

Birth and Perinatal History:

The patient was delivered at full term through normal vaginal delivery (FTVD) with a birth weight of 2.5 kg. The antenatal, perinatal, and intrapartum periods were uneventful, with no maternal or fetal complications reported. The child did not require neonatal intensive care, and the neonatal period was smooth. There was no history of birth asphyxia, delayed cry, or neonatal seizures.

Clinical findings

Vital Signs:

On examination, the child was alert and oriented. Vital parameters were assessed as follows:

  • Temperature: 98.9°F – slightly elevated, though not meeting the clinical threshold for fever
  • Heart Rate: Within normal limits for age
  • Respiratory Rate: Normal
  • Blood Pressure: Within age-appropriate range
  • Oxygen Saturation (SpO?): Normal on room air

Overall, vital signs were stable at the time of examination, with mildly elevated body temperature being the only notable finding.

Systemic Examination

Head-to-Toe Examination:

  • Head: Normal shape and size; no signs of trauma, swelling, or tenderness
  • Scalp: Clean; no lesions or abnormalities
  • Face: Symmetrical; no craniofacial anomalies
  • Eyes: Normal; conjunctiva and sclera appear healthy, pupils equal and reactive to light; no signs of icterus or pallor
  • Ears: Normal; no discharge, inflammation, or tenderness noted
  • Nose: Patent; no nasal congestion or discharge
  • Mouth and Throat: Mucosa moist; no ulcers or inflammation; no signs of dehydration

Neck:

    • No lymphadenopathy
    • Trachea centrally positioned
    • No neck stiffness or rigidity
    • Thyroid not palpable

Anthropometry

Table: 1 Anthropometric Measurements of the Patient

Parameter

Observed Value

Expected Value

Centile

Interpretation

Weight

21 kg

39.0 kg

< 3rd

Underweight

Height

101 cm

114.4 cm

3rd–10th

Stunted growth (mild)

BMI

11.1 kg/m²

17.7 kg/m²

< 3rd

Severe undernutrition

Overall Interpretation: The child demonstrates chronic undernutrition, with weight and BMI both below the 3rd centile and height between the 3rd–10th centile, predisposing to increased susceptibility and complications from infections like Japanese Encephalitis.

Systemic Examination (continued):

Respiratory System:

  • Trachea: Central in position with no deviation.
  • Chest Expansion: Bilateral chest movements were symmetrical and adequate.
  • Air Entry: Equal and adequate on both sides.
  • Breath Sounds: Normal vesicular breath sounds were heard throughout the lung fields.
  • Adventitious Sounds: No added sounds such as wheeze, crepitation’s, or crackles were detected.
  • Chest Wall: No scars, sinuses, deformities, or abnormal visible movements were present.

Cardiovascular System:

  • Precordium: Normal in contour and appearance; no abnormal visible pulsations, heaves, or chest wall deformities noted.
  • Apex Beat: Localized in the 4th intercostal space along the midclavicular line, well-defined and not displaced.
  • Heart Sounds: Both first (S1) and second (S2) heart sounds were clearly audible, normal in intensity and character.
  • Murmurs/Added Sounds: No pathological murmurs, rubs, or additional heart sounds were detected on auscultation.
  • Peripheral Pulses: All peripheral pulses were palpable, present, and equal bilaterally with no delay or asymmetry.

Central Nervous System Examination:

Neurological Examination

On admission, a detailed neurological evaluation was performed:

  • Consciousness and Orientation: The child was conscious, alert, and oriented to time, place, and person, with no alteration in higher mental functions at the time of examination.
  • Cranial Nerves:
    • CN I (Olfactory): Not assessed.
    • CN II (Optic): Pupils equal, round, and reactive to light bilaterally (BERL +); visual acuity grossly normal. Fundoscopy was not performed at admission.
    • CN III, IV, VI (Oculomotor, Trochlear, Abducens): Extraocular movements were full and intact in all directions of gaze, with no evidence of diplopia or nystagmus.
    • CN V (Trigeminal): Bilateral facial sensations were intact across ophthalmic, maxillary, and mandibular divisions. Corneal reflex was preserved.
    • CN VII (Facial): Symmetrical facial movements were observed, with no evidence of facial weakness.
    • CN VIII (Vestibulocochlear): Hearing was normal for conversational voice; no vertigo or balance disturbance reported.
    • CN IX, X (Glossopharyngeal and Vagus): Gag reflex present and normal; palatal movements were symmetrical. No dysphonia or dysphagia noted.
    • CN XI (Accessory): Shoulder shrug and head rotation against resistance were normal bilaterally.
    • CN XII (Hypoglossal): Tongue was midline with normal movements, no fasciculations or atrophy noted.
  • Cerebellar Functions: Coordination and balance were preserved. Finger-to-nose and heel-to-shin tests were normal. No signs of ataxia, intention tremor, or dysmetria were detected. Gait was steady for age.
  • Signs of Meningeal Irritation:
    • Neck rigidity: Positive.
    • Kernig’s sign: Positive.
    • Brudzinski’s sign: Positive.

Developmental History:

  • The child is currently attending school and is reported to be performing well academically.
  • There is no history of developmental delay or regression noted at any point.

Diet history

Table: 2 Diet history

Timimgs

Food

Calories

Protein

Morning

Milk

Idli

Sambar

60

41

162

6

2

4

Afternoon

Chapati

Curry

Egg

54

172

60

3

3

6

Evening

Milk

60

6

Night

Chapati

Rice

Curry

54

162

172

3

4

3

 

Required

Deficient

937

10%

40

9%

Nutritional Assessment:

  • Total calories consumed: 937 kcal/day
  • Total protein consumed: 40 g/day

According to the Indian Council of Medical Research (ICMR) guidelines, the child’s estimated caloric requirement is 1037 kcal/day.

This indicates a caloric deficit of approximately 10%, suggesting the child is currently undernourished and not meeting the recommended energy intake for his age and activity level.

Investigations

Laboratory Investigations

Table: 3 Laboratory Investigations

Parameter

Observed Value

Reference Range

Interpretation

Hemoglobin (Hb)

11.4 g/dL

12–16 g/dL

Mild anemia

Total Leukocyte Count (TLC)

4300 cells/cmm

4000–11000 cells/cmm

Within normal limits; slightly on the lower side

Platelet Count

1.75 lakh/cmm

1.5–4.5 lakh/cmm

Normal

RBC Count

4.76 million/cmm

4.5–5.5 million/cmm

Normal

Packed Cell Volume (PCV)

35%

36–46%

Slightly low

Differential Leukocyte Count (DLC)

43% Neutrophils / 46% Lymphocytes

Neutrophils 40–70%, Lymphocytes 20–45%

Mild relative lymphocytosis

Sodium (Na?)

129 mEq/L

135–145 mEq/L

Mild hyponatremia

Potassium (K?)

3.9 mEq/L

3.5–5.0 mEq/L

Normal

Interpretation in Context of Japanese Encephalitis:

  • Mild anemia and slightly reduced PCV are consistent with nutritional status (underweight/undernourished child) rather than the acute infection.
  • TLC is within normal limits, but the relative lymphocytosis may suggest a viral etiology, which aligns with the confirmed diagnosis of Japanese Encephalitis.
  • Mild hyponatremia could be due to systemic infection or early syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is sometimes observed in viral encephalitis.
  • Platelets and other hematological parameters are within normal range, indicating no significant hematologic involvement.

Renal Function Tests (RFTs)

Table: 4 Renal Function Tests

Parameter

Observed Value

Reference Range

Interpretation

Blood Urea

16 mg/dL

15–40 mg/dL

Normal

Serum Creatinine

0.8 mg/dL

0.5–1.0 mg/dL

Normal

Interpretation: The renal function tests were within normal limits, indicating preserved kidney function. There is no evidence of renal involvement in this child presenting with Japanese Encephalitis.

Diagnosis:

Cerebrospinal Fluid (CSF) Analysis:

  • Cell Count: 900 cells/mm³
  • Cell Type: Predominantly lymphocytes (90%), with few monocytes (10%)

Impression: Smear shows a predominance of lymphocytes against a proteinaceous background; Japanese Encephalitis (JE) positive

  • CSF Glucose: 41 mg/dL
  • CSF Protein: 78 mg/dL (elevated)
  • CSF Chloride: 115 mmol/L
  • CSF Gram Stain: Normal (no bacteria visualized)
  • CSF Ziehl-Neelsen Stain: Negative for acid-fast bacilli (no evidence of tuberculosis)

Treatment

Table :5 Treatment chart

Drug names

Dose

R. O. A

Frequency

Days

IVF DNS

60ml

IV

Per hour

3days

Inj Ceftriaxone

2.1g

IV

1-0-1

17days

Inj Amikacin

160mg

IV

1-0-1

17days

Inj Ranitidine

40mg

IV

QD

10days

Inj Dexamethasone

1mg

IV

0-1-0

7days

Inj Acyclovir

400mg

IV

1-1-1

5days

Syp Multivitamin

5ml

PO

1-0-1

6days

Syp Calcium

5ml

PO

1-0-1

4days

Inj pantoprazole

40mg

IV

1-0-1

6days

There is no specific antiviral therapy for JE and vaccination is the only reliable option for its prevention and control. In the available vaccine, most common vaccine against JEV genotype III (GIII) is used across endemic countries. The clinical management mainly focuses on supportive care and symptomatic relief.13

The patient was treated with the following medications from the first day of admission to the thirteenth day of discharge: Ceftriaxone injection 2.1 g twice daily, Amikacin injection 160 mg twice daily, and Ranitidine injection 40 mg twice daily from the first day to the tenth day. Dexamethasone injection 1 mg four times daily was administered from the second day to the seventh day, and Acyclovir injection 400 mg three times daily was given from the third day to the seventh day. Supportive care included intravenous fluids (DNS) at 660 ml/hour for three days, oral rehydration solution (ORS) for seven days, multivitamin syrup 5 ml once daily for six days, and calcium syrup 5 ml three times daily for six days were given. The danger signs were explained, and the patient was advised to seek immediate medical attention if there was any elevation in body temperature (fever spike) and to visit the pediatric outpatient department for a follow-up after one week.

DISCUSSION:

The diagnosis of Japanese encephalitis virus (JEV) infection posed significant challenges due to the rarity of detecting JEV RNA in blood or cerebrospinal fluid (CSF) samples. Typically, serological tests formed the basis for diagnosis, but their interpretation was often complicated by non-specific reactivity, cross-reactivity with other flaviviruses, and persistence of antibodies from prior infections or immunizations. In many cases, patients sought medical attention only after neurological symptoms emerged, by which time the acute phase of the infection had often passed, and viral clearance had occurred. However, in the reported case, analysis of the patient’s CSF revealed the presence of JEV, with a smear showing predominantly lymphocytes, a few monocytes, and a proteinaceous background, confirming a positive JEV diagnosis.

The patient, a previously healthy child, presented with a history of headache, nausea, vomiting, mild to moderate fever, and giddiness that began five days prior to admission. These symptoms, including bilateral diurnal variation and giddiness exacerbated by standing or walking, aligned with clinical manifestations of JEV infection. Initial treatment at a district hospital in Haveri with ceftriaxone and amikacin did not fully resolve the symptoms, particularly giddiness, prompting transfer to KMCRI in Hubli. There, physicians considered differential diagnoses of Japanese encephalitis and viral meningoencephalitis. Based on a provisional diagnosis of viral meningoencephalitis, the patient received ceftriaxone (100 mg/kg/dose) and amikacin (150 mg/kg/dose), which led to a gradual reduction in symptoms, although giddiness persisted.

A similar case occurred in rural West Bengal, India, involving an 11-year-old girl who initially experienced high-grade fever, chills, severe headache, neck stiffness, and vomiting. Her parents sought treatment from an unqualified practitioner, but the intervention failed to alleviate her symptoms. On the third day of illness, the patient developed seizures and lapsed into unconsciousness, leading to her hospitalization and subsequent diagnosis of JEV infection.

Japanese encephalitis remained one of the most severe viral infections endemic to Asia, causing significant morbidity and mortality. The absence of specific antiviral treatments for JEV underscored the critical importance of prevention. Preventive strategies primarily included vector control, pig immunization, and human immunization. In India, vector control served as the cornerstone of prevention efforts, but vaccination offered the most effective long-term protection against JEV. As no therapies directly targeted the virus, clinical management focused on addressing symptoms and complications. The ongoing lack of specific antiviral drugs highlighted the urgent need for continued research to develop targeted treatments for JEV infection.

CONCLUSION:

This case underscores the clinical complexity and public health importance of Japanese encephalitis (JE), especially among pediatric populations in endemic areas. The early signs of fever, headache, vomiting, and giddiness in the patient progressed to classical meningeal signs, highlighting the need for high clinical suspicion and timely diagnostic evaluation. Despite the lack of specific antiviral therapy, supportive management—including antibiotics, antiviral, corticosteroids, and nutritional support—played a crucial role in the patient's recovery. The diagnosis was confirmed through cerebrospinal fluid analysis revealing lymphocytic Pleocytosis and JE positivity. This case reiterates the urgent need for increased awareness, early diagnosis, and above all, preventive measures such as vaccination and vector control strategies to mitigate the burden of JE, especially in vulnerable, underserved populations.

REFERENCE

  1. Rajaiah P, Kumar A. Japanese encephalitis virus in India: An update on virus genotypes. Indian J Med Res 2022;156:588-97.
  2. Burke DS, Leake CJ. Japanese encephalitis. In: Arboviruses. CRC Press; 2019. p. 63-92.
  3. Simmonds P, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff S, Pletnev A, Rico-Hesse R, Smith DB, Stapleton JT. ICTV virus taxonomy profile: Flaviviridae. J Gen Virol 2017;98:2-3.
  4. Mackenzie JS, Williams DT, van den Hurk AF, Smith DW, Currie BJ. Japanese encephalitis virus: the emergence of genotype IV in Australia and its potential endemicity. Viruses 2022;14:2480.
  5. Billoir F, de Chesse R, Tolou H, de Micco P, Gould EA, de Lamballerie X. Phylogeny of the genus Flavivirus using complete coding sequences of arthropod-borne viruses and viruses with no known vector. J Gen Virol 2000;81:781-90.
  6. Quan TM, Thao TT, Duy NM, Nhat TM, Clapham H. Estimates of the global burden of Japanese encephalitis and the impact of vaccination from 2000-2015. Elife 2020;9:e51027.
  7. Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, Marfin AA, Solomon T, Tsai TF, Tsu VD, Ginsburg AS. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ 2011;89:766-74.
  8. Schiøler KL, Samuel M, Wai KL. Vaccines for preventing Japanese encephalitis. Cochrane Database Syst Rev 2007;CD004263.
  9. Jn H. Japanese encephalitis in north Queensland, Australia, 1998. Med J Aust 1999;170:533-6.
  10. Pearce JC, Learoyd TP, Langendorf BJ, Logan JG. Japanese encephalitis: the vectors, ecology and potential for expansion. J Travel Med 2018;25:S16-26.
  11. Adarsh GS, Wari PK, Kulkarni PV, Ratageri V, Shivanand I, Siddappa FD. Acid Sphingomyelinase Deficiency: A Review. Eur J Pharm Med Res 2024;11:520–525.
  12. Ricklin ME, García-Nicolás O, Brechbühl D, Python S, Zumkehr B, Nougairede A, Charrel RN, Posthaus H, Oevermann A, Summerfield A. Vector-free transmission and persistence of Japanese encephalitis virus in pigs. Nat Commun 2016;7:10832.

Reference

  1. Rajaiah P, Kumar A. Japanese encephalitis virus in India: An update on virus genotypes. Indian J Med Res 2022;156:588-97.
  2. Burke DS, Leake CJ. Japanese encephalitis. In: Arboviruses. CRC Press; 2019. p. 63-92.
  3. Simmonds P, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff S, Pletnev A, Rico-Hesse R, Smith DB, Stapleton JT. ICTV virus taxonomy profile: Flaviviridae. J Gen Virol 2017;98:2-3.
  4. Mackenzie JS, Williams DT, van den Hurk AF, Smith DW, Currie BJ. Japanese encephalitis virus: the emergence of genotype IV in Australia and its potential endemicity. Viruses 2022;14:2480.
  5. Billoir F, de Chesse R, Tolou H, de Micco P, Gould EA, de Lamballerie X. Phylogeny of the genus Flavivirus using complete coding sequences of arthropod-borne viruses and viruses with no known vector. J Gen Virol 2000;81:781-90.
  6. Quan TM, Thao TT, Duy NM, Nhat TM, Clapham H. Estimates of the global burden of Japanese encephalitis and the impact of vaccination from 2000-2015. Elife 2020;9:e51027.
  7. Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, Marfin AA, Solomon T, Tsai TF, Tsu VD, Ginsburg AS. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ 2011;89:766-74.
  8. Schiøler KL, Samuel M, Wai KL. Vaccines for preventing Japanese encephalitis. Cochrane Database Syst Rev 2007;CD004263.
  9. Jn H. Japanese encephalitis in north Queensland, Australia, 1998. Med J Aust 1999;170:533-6.
  10. Pearce JC, Learoyd TP, Langendorf BJ, Logan JG. Japanese encephalitis: the vectors, ecology and potential for expansion. J Travel Med 2018;25:S16-26.
  11. Adarsh GS, Wari PK, Kulkarni PV, Ratageri V, Shivanand I, Siddappa FD. Acid Sphingomyelinase Deficiency: A Review. Eur J Pharm Med Res 2024;11:520–525.
  12. Ricklin ME, García-Nicolás O, Brechbühl D, Python S, Zumkehr B, Nougairede A, Charrel RN, Posthaus H, Oevermann A, Summerfield A. Vector-free transmission and persistence of Japanese encephalitis virus in pigs. Nat Commun 2016;7:10832.

Photo
Adarsh G. S.
Corresponding author

Soniya Education Trust’s College of Pharmacy, Dharwad, Karnataka, India.

Photo
Tanuja S. L.
Co-author

Soniya Education Trust’s College of Pharmacy, Dharwad, Karnataka, India.

Photo
Siddappa Dandinavar
Co-author

Department of Pediatrics, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India.

Photo
Preeti V. Kulkarni
Co-author

Soniya Education Trust’s College of Pharmacy, Dharwad, Karnataka, India.

Photo
Venkatrao H. Kulkani
Co-author

Soniya Education Trust’s College of Pharmacy, Dharwad, Karnataka, India.

Photo
Thrinesh B. R.
Co-author

Soniya Education Trust’s College of Pharmacy, Dharwad, Karnataka, India.

Tanuja S. L., Adarsh G. S.*, Siddappa Dandinavar, Preeti V. Kulkarni, Venkatrao H. Kulkani, Thrinesh B. R., A Rare Pediatric Case of Japanese Encephalitis Presenting with Acute Febrile Encephalopathy, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 10, 465-474 https://doi.org/10.5281/zenodo.17276839

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