Clinical history
A 4-month-old boy was previously admitted to a Victorian pediatric tertiary hospital in February 2022 after a febrile seizure. It had a 2-day prodrome characterized by fever at 39 ° C and reduced energy and feeding. Self-limiting febrile seizure occurred on day 3 of the disease and was characterized by deviation of the left eye, tonic extension of the upper extremities, shallow breathing, and pallor. On initial examination it did not look bad and no convincing source of fever was identified. It was born out and developed appropriately for age.
Initial laboratory research was significant for mild thrombocytosis and blood film, with occasional reactive lymphocytes. White blood cell count, red blood cell count, serum inflammatory markers, electrolytes, ketones, glucose, and liver function were not remarkable. Ceftriaxone, flucloxacillin, and acyclovir were initiated before lumbar puncture as an empirical treatment for sepsis with additional antiviral coverage. Lumbar puncture on day 1 of admission showed predominant pleocytosis in lymphocytes with high protein and decreased glucose (Table 1). Initial microbiological investigations did not identify any causative pathogens; these included Gram staining and bacterial culture of cerebrospinal fluid (CSF), BioFire FilmArray (Biomérieux) meningitis / encephalitis panel, and internal herpes simplex virus (PCR) polymerase chain reaction. Blood and urine culture and a respiratory panel, tested in a deep nasal / oral sample in a commercial respiratory panel (16-well respiratory pathogen board [Ref 20620]AusDiagnostics), were also negative.
The patient continued to have more seizures of similar semiology, requiring levetiracetam, phenobarbital, and phenytoin. Levetiracetam maintenance was started on the 3rd day of admission, with seizure resolution.
On day 4 of admission, an electroencephalogram (EEG) showed a slower activity, of less amplitude and poorly organized, with a focal slowdown in the right posterior temporal region. Magnetic resonance imaging (MRI) of the brain showed a change in signal with restricted diffusion of the bilateral thalamus and diffuse pachymeningeal improvement.
Investigations for the Japanese encephalitis virus (JEV) began on the 14th of admission in response to a public health alert for detection of JEV in Victoria. CSF from day 1 of admission was positive in a pan-flavivirus PCR assay and was subsequently identified as JEV by Sanger sequencing. Serum serology of convalescent Japanese encephalitis B virus was IgG positive (Table 2). Retrospective history identified mosquito exposure during a trip to a city on the border of Victoria and New South Wales, 15 days before the onset of symptoms. Other family members remained asymptomatic. Clinically, the patient returned close to initial neurological function with some residual weakness but slight improvement in the upper left limb. It was planned for daily levetiracetam and close monitoring of neurological development.
Discussion
To our knowledge, this is the first reported case of Japanese encephalitis in a Victorian baby, reflecting a growing epidemic involving the spread to new regions of Australia. In late February 2022, JEV was detected in pigs in Victoria, Queensland, and New South Wales.1 As of May 4, 2022, there have been 38 human cases of Japanese encephalitis in Australia, including four deaths. 2 To date, most of these cases have occurred in adults. This is consistent with established data that symptomatic infections in children predominate in endemic areas, but occur in both children and adults in newly affected regions.3
JEV infection is most often asymptomatic. This case describes a typical symptomatic presentation (1% of infections) characterized by an incubation period of 5 to 15 days, a nonspecific prodrome of 2 to 4 days followed by a progression to aseptic meningoencephalitis. and are more common in children compared to adults.3 Our patient also demonstrated characteristic research results, such as predominant CSF pleocytosis in lymphocytes, deceleration of diffuse EEG, and bilateral thalamic lesions on MRI.3 There are no specific treatments and management should focus on support. attention, close monitoring of neurodevelopment, and early intervention. Pediatric patients may present with normal discharge development, with deficits that only appear as neurodevelopment progresses. The disease in the extremes of age gives a worse prognosis; however, this is based on small case series and there is little data on specific baby outcomes in the literature. In general, neurological sequelae occur in approximately 50% of patients with Japanese encephalitis, with motor deficits, cognitive deficits, and seizures.3
Despite its high morbidity and mortality, little progress has been made in the last decade to investigate new treatments for Japanese encephalitis. There have only been four clinical trials that included the random assignment of fewer than 400 patients with proven Japanese encephalitis.5 In contrast, a current approach to prevention is essential. There are two vaccines against JEV in Australia: Imojev (Sanofi ‐ Aventis Australia), a live attenuated vaccine available for people under ≥ 9 months, and JEspect (Seqirus), an inactivated vaccine available from 2 months of age in a two-dose program. 6 In response to the current outbreak, Australian vaccination recommendations have been expanded to include people involved in the care or handling of pigs and mosquitoes or people ≥ 2 months of age residing in high-risk Australian settings.7
Over the past two decades, there has been growing evidence that climate emergencies are a driving force in the spread of waterborne and zoonotic diseases.8 Because sentinel pigs were known to test positive for JEV for a period of time. of time before current human cases. , this highlights the need to strengthen the One Health approach to the human-animal-environment interface.
Practice lessons
- • There is an evolving Japanese encephalitis epidemic in Australia; This diagnosis should now be considered in all patients with meningoencephalitis in whom no alternative causal pathogen has been identified, especially when there are epidemiological risk factors.
- • Infection with the Japanese encephalitis virus is more often asymptomatic, but when there is a clinical disease it can lead to significant morbidity and mortality.
- • Typical research findings include predominant lymphocyte pleocytosis, diffuse electroencephalogram deceleration, and bilateral thalamic MRI lesions.
Table 1 – Results of cerebrospinal fluid
Component
Result (reference range)
Polymorphs, × 106 / L
10 (0)
Lymphocytes, × 106 / L
233 (5)
Total white blood cell count, × 106 / L
243 (0–5)
Red blood cell count, × 106 / L
3 (0)
Protein, g / L
0.46 (0.20–0.40)
Glucose of cerebrospinal fluid, mmol / L
2.7 (2.8–4.0)
Macroscopic
Clear and colorless
Culture
No growth after 5 days
Table 2: Tests for the Japanese encephalitis virus
Sickness day
Show
Try it
Result
3
CSF
Serology of the Japanese B encephalitis virus
Negative IgG (<10), IgM not detected
3
CSF
Flavivirus RT-PCR
Detected; identified as the Japanese encephalitis virus by Sanger sequencing
12
Serum
Serology of the Japanese B encephalitis virus
Negative IgG (<10), IgM not detected
12
Serum
Flavivirus RT-PCR
Not detected
16
Urine
Flavivirus RT-PCR
Not detected
20
Serum
Serology of the Japanese B encephalitis virus
Positive IgG (titer ≥ 10), undetected IgM
CFS = cerebrospinal fluid, RT-PCR = reverse transcription polymerase chain reaction.