Japońskie zapalenie mózgu
Diagnostyka i diagnoza

Japońskie zapalenie mózgu (JE) jest główną przyczyną wirusowego zapalenia mózgu u dzieci w Azji i regionie zachodniego Pacyfiku, a jego diagnostyka opiera się na ocenie klinicznej oraz badaniach laboratoryjnych. Podejrzenie JE powinno być rozważane u pacjentów z objawami zapalenia mózgu, zapalenia opon mózgowo-rdzeniowych lub wiotkiego porażenia, którzy przebywali na terenach endemicznych. Diagnostyka laboratoryjna bazuje przede wszystkim na wykrywaniu przeciwciał IgM przeciwko wirusowi JE w płynie mózgowo-rdzeniowym (CSF) lub surowicy za pomocą testu MAC-ELISA, z czułością około 70% w pierwszym tygodniu i 95% po 10 dniach od początku objawów. Analiza CSF typowo wykazuje umiarkowaną limfocytarną pleocytozę, podwyższone białko oraz prawidłowy lub nieznacznie obniżony stosunek glukozy w CSF do osocza. Metody molekularne, takie jak RT-PCR i RT-LAMP, choć mniej czułe z powodu krótkotrwałej wiremii, stanowią uzupełnienie diagnostyki, a badania obrazowe (MRI, CT) wskazują na charakterystyczne zmiany w obrębie wzgórza, jąder podstawy i hipokampa.

Diagnostyka japońskiego zapalenia mózgu

Japońskie zapalenie mózgu (JE) jest wiodącą przyczyną wirusowego zapalenia mózgu u dzieci w Azji i regionie zachodniego Pacyfiku. Diagnoza tego schorzenia może być wyzwaniem ze względu na niespecyficzne objawy, szczególnie w początkowej fazie choroby. Właściwa diagnostyka jest kluczowa dla potwierdzenia zakażenia i wykluczenia innych przyczyn zapalenia mózgu.12

Badania kliniczne i podejrzenie JE

Podejrzenie japońskiego zapalenia mózgu powinno być wysunięte u pacjentów z objawami zapalenia mózgu, zapalenia opon mózgowo-rdzeniowych lub wiotkiego porażenia, którzy mieszkają lub przebywali na terenach endemicznych.34 Diagnoza początkowo opiera się na ocenie klinicznej, przy uwzględnieniu informacji o miejscu zamieszkania pacjenta oraz ewentualnych podróżach do obszarów występowania wirusa.56

Według definicji Światowej Organizacji Zdrowia (WHO), przypadek podejrzany o JE to osoba, która mieszka lub podróżowała do obszaru endemicznego JE i doświadcza objawów zapalenia mózgu. Definicja kliniczna ostrego zespołu zapalenia mózgu (AES) obejmuje ostrą gorączkę oraz przynajmniej jedną z następujących cech: zmiana stanu psychicznego (dezorientacja, splątanie, śpiączka lub niezdolność do mówienia) lub nowe napady drgawkowe (z wyłączeniem prostych drgawek gorączkowych).78

Badania laboratoryjne

Diagnoza laboratoryjna JE opiera się głównie na badaniach serologicznych, które polegają na wykrywaniu przeciwciał przeciwko wirusowi, zwłaszcza immunoglobulin klasy M (IgM).19

Test MAC-ELISA (IgM Antibody Capture Enzyme-Linked Immunosorbent Assay) jest najbardziej powszechnie stosowaną metodą diagnostyczną, rekomendowaną przez WHO.27 Test ten wykrywa przeciwciała IgM specyficzne dla wirusa JE w płynie mózgowo-rdzeniowym (CSF) lub surowicy krwi. Badanie CSF jest preferowane, ponieważ bezpośrednio potwierdza zajęcie ośrodkowego układu nerwowego i zmniejsza ryzyko wyników fałszywie dodatnich związanych z wcześniejszym zakażeniem lub szczepieniem.110

Przeciwciała IgM przeciwko wirusowi JE są zazwyczaj wykrywalne w CSF już 3-4 dni po wystąpieniu objawów, a w surowicy po 4-7 dniach. Czułość wykrywania IgM w CSF wynosi około 70% w pierwszym tygodniu i około 95% po 10 dniach od początku choroby.711 Przeciwciała te utrzymują się w organizmie przez 30-90 dni, choć odnotowano przypadki dłuższego utrzymywania się.912

Badanie PŁCR i cechy diagnostyczne

Badanie płynu mózgowo-rdzeniowego jest kluczowe dla diagnostyki JE. Punkcja lędźwiowa powinna być wykonana u wszystkich pacjentów z podejrzeniem zapalenia mózgu, o ile nie ma przeciwwskazań.13 W JE, analiza PŁCR typowo wykazuje:148

1415

Warto zaznaczyć, że opisano przypadki JE z prawidłowym wynikiem badania PŁCR, gdzie diagnoza została potwierdzona metodą PCR. Podkreśla to znaczenie utrzymania wysokiego stopnia podejrzenia klinicznego w obszarach endemicznych, nawet przy braku typowych zmian w PŁCR.15

Testy molekularne

Metody molekularne, takie jak reakcja łańcuchowa polimerazy z odwrotną transkryptazą (RT-PCR), mogą być stosowane do wykrywania materiału genetycznego wirusa JE, chociaż ich czułość jest ograniczona ze względu na krótkotrwałą wiremię i niskie miano wirusa we krwi.716

RT-PCR może być wykonany na próbkach krwi, PŁCR, a także na innych płynach ustrojowych, jak wymazy z gardła.1718 Wykrycie RNA wirusa JE jest wysoce specyficzne dla potwierdzenia zakażenia JE.17

Nowsze techniki molekularne, jak izotermalna amplifikacja pośredniczona przez pętlę z odwrotną transkryptazą (RT-LAMP), zapewniają czułość porównywalną z real-time RT-PCR, a przy tym są prostsze i mniej czasochłonne.19

Badania obrazowe

Badania obrazowe, szczególnie rezonans magnetyczny (MRI), odgrywają istotną rolę w diagnostyce JE, choć nie są specyficzne dla tego schorzenia.420

Charakterystyczne zmiany w obrazie MRI w JE to:218

  • Obustronne hiperintensywne zmiany w obrębie wzgórza, często symetryczne
  • Zajęcie jąder podstawy, śródmózgowia lub hipokampa
  • W ciężkich przypadkach mogą być widoczne zmiany krwotoczne

21

Tomografia komputerowa (CT) może wykazywać obszary zmniejszonej gęstości w podobnych lokalizacjach lub powikłania, takie jak obrzęk mózgu czy wodogłowie.8

Diagnostyka różnicowa

Jednym z wyzwań w diagnostyce JE jest reaktywność krzyżowa przeciwciał z innymi flawiwirusami, takimi jak wirus dengi czy wirus Zachodniego Nilu, które mogą współwystępować na tych samych obszarach geograficznych.222

Do rozstrzygnięcia reaktywności krzyżowej stosuje się test neutralizacji redukcji łożyska (PRNT), który jest najbardziej specyficznym testem serologicznym.2324 Czterokrotny wzrost miana przeciwciał neutralizujących specyficznych dla wirusa JE, wykryty w dwóch próbkach surowicy pobranych w odstępie 14 dni, potwierdza niedawne zakażenie JE.24

Opracowano również algorytmy diagnostyczne, które łączą różne testy, np. sekwencyjne testowanie z użyciem zestawów JE Detect i DEN Detect, co zwiększa specyficzność dla JE w surowicy.2525

Dodatkowe metody diagnostyczne

W przypadkach śmiertelnych, diagnoza może być potwierdzona poprzez:10

  • Amplifikację kwasów nukleinowych z tkanek pobranych podczas autopsji
  • Histopatologię z immunohistochemią
  • Hodowlę wirusa z tkanek mózgu

1012

Antygeny wirusowe można wykryć w tkankach za pomocą barwienia metodą immunofluorescencji pośredniej.9

Wyzwania diagnostyczne

Diagnostyka JE napotyka na szereg wyzwań:1326

  • Reaktywność krzyżowa z przeciwciałami przeciwko innym flawiwirusom, zwłaszcza wirusowi dengi
  • Możliwość fałszywie dodatnich wyników u osób szczepionych przeciwko JE lub zainizywanych innymi flawiwirusami
  • Ograniczona czułość testów PCR ze względu na krótkotrwałą wiremię
  • Negatywne wyniki badań w początkowych dniach choroby
  • Ograniczona dostępność zaawansowanych testów diagnostycznych w obszarach endemicznych

227

Postępowanie diagnostyczne

Optymalny protokół diagnostyczny dla podejrzenia JE powinien obejmować:2829

  • Pobranie próbek surowicy i PŁCR w ostrej fazie choroby
  • Wykonanie testu MAC-ELISA na obecność przeciwciał IgM w PŁCR
  • W przypadku negatywnego wyniku – powtórzenie badania na próbce pobranej w fazie zdrowienia (2-4 tygodnie od początku objawów)
  • Przeprowadzenie testów RT-PCR na próbkach PŁCR, krwi lub wymazach z gardła, szczególnie we wczesnej fazie choroby
  • W przypadku wykrycia przeciwciał IgM – wykonanie testów potwierdzających (PRNT)
  • Równoległe badania w kierunku innych możliwych przyczyn zapalenia mózgu

2829

Podsumowanie

Diagnostyka japońskiego zapalenia mózgu wymaga połączenia oceny klinicznej, badań laboratoryjnych i obrazowych. Test MAC-ELISA wykrywający przeciwciała IgM w płynie mózgowo-rdzeniowym pozostaje metodą z wyboru, jednak ze względu na ograniczenia tej metody, wskazane jest stosowanie dodatkowych testów potwierdzających, takich jak PRNT czy techniki molekularne. Ważne jest również wykonywanie badań różnicowych w kierunku innych przyczyn zapalenia mózgu, szczególnie innych infekcji flawiwirusowych.208

Mimo postępów w diagnostyce, japońskie zapalenie mózgu pozostaje wyzwaniem diagnostycznym, szczególnie w regionach o ograniczonym dostępie do zaawansowanych metod laboratoryjnych. Szczepienia przeciwko JE są nadal najskuteczniejszą metodą zapobiegania infekcji, zwłaszcza w obszarach endemicznych.2030

Kolejne rozdziały

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Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

  1. 17.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1
    https://www.who.int/news-room/fact-sheets/detail/japanese-encephalitis
    Individuals who live in or have travelled to a JE-endemic area and experience encephalitis are considered a suspected JE case. Initial diagnosis of JE can be made by clinical examination followed by a lumbar puncture. A laboratory test is required to confirm JEV infection and to rule out other causes of encephalitis. WHO recommends testing for JEV-specific IgM antibody in a single sample of cerebrospinal fluid (CSF) or serum, using an IgM-capture ELISA. If tested negative, a convalescent sample may be tested. Testing of CSF sample is preferred to reduce false-positivity rates from previous infection or vaccination. […] Surveillance of the disease is mostly syndromic for acute encephalitis syndrome. Confirmatory laboratory testing is often conducted in dedicated sentinel sites, and efforts are undertaken to expand laboratory-based surveillance. Case-based surveillance is established in countries that effectively control JE through vaccination.
  • #2 Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4824224/
    Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. […] The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JE Detect and DEN Detect and were classified as JE (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JE Detect and DEN Detect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF.
  • #2 Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4824224/
    There is considerable cross-reactivity in the CDC JEV and DENV MAC-ELISA, which is why the PRNT is an essential confirmatory test in the CDC differential diagnostic testing algorithm. […] However, because the numbers of DEN IgM+ CSF samples in these evaluations was small and the DEN Detect kit is not intended for CSF testing, further investigation is warranted before any conclusions can be made on the usefulness of the DEN Detect kit for differential diagnosis of JEV infections with CSF samples.
  • #3 Japanese Encephalitis | Encephalitis International
    https://www.encephalitis.info/types-of-encephalitis/infectious-encephalitis/japanese-encephalitis/
    The symptoms of Japanese encephalitis are not specific for this illness. People living/travelling in the endemic areas should be suspected and tested for JEV if they present with symptoms of encephalitis (fever, seizures, a change in consciousness level or neurological signs). Diagnosis can be confirmed, usually, by finding specific antibodies in the cerebrospinal fluid (CSF) following a lumbar puncture (LP or spinal tap) or in the blood.
  • #4 Japanese encephalitis clinical update: Changing diseases under a changing climate
    https://www1.racgp.org.au/ajgp/2023/may/japanese-encephalitis-clinical-update
    JE should be suspected in cases of encephalitis, meningitis or flaccid paralysis. […] Diagnosis of JEV is challenging due to limitations in the sensitivity and specificity of diagnostic tests. Polymerase chain reaction (PCR) tests for JEV can be performed on cerebrospinal fluid (CSF) or other samples (whole blood, urine, serum) and, if positive, are confirmatory. […] The detection of JEV IgM in CSF is considered to be the gold standard for diagnosis, and, if present, is consistent with a diagnosis of JE. […] A diagnosis of JE can also be confirmed by the demonstration of seroconversion or a rising IgG titre on serial blood samples. […] The interpretation of serological testing is complicated by the fact that antibodies against JE and other flaviviruses are highly cross-reactive. […] Testing should be discussed with the relevant laboratory or infectious diseases service before ordering.
  • #4 Japanese encephalitis clinical update: Changing diseases under a changing climate
    https://www1.racgp.org.au/ajgp/2023/may/japanese-encephalitis-clinical-update
    Although not diagnostic, abnormalities may be seen on magnetic resonance imaging, whereby JE causes parenchymal inflammation, which classically affects the bilateral thalami and can also involve the basal ganglia and brain stem. […] Investigations should also seek to identify alternative causes of meningoencephalitis and/or flaccid paralysis, as reviewed in detail elsewhere.
  • #5 Japanese encephalitis: Symptoms, treatment, transmission, and more
    https://www.medicalnewstoday.com/articles/181418
    To diagnose Japanese encephalitis, the doctor will examine any symptoms, verify where the individual lives, and ask about the destinations of any recent visits from which the infection could have emerged. […] If a doctor suspects encephalitis, the patient will undergo tests, such as a CT or MRI scan of the brain. […] The physician might use a lumbar puncture or spinal tap to draw fluid from the spine. The results can show which virus is causing the encephalitis. […] Immunofluorescence tests can detect human antibodies. The antibodies show up after the doctor tags them with a fluorescent chemical.
  • #6 Diagnosing Japanese encephalitis | Hospital Clínic Barcelona
    https://www.clinicbarcelona.org/en/assistance/diseases/japanese-encephalitis/diagnosis
    The diagnosis is based on clinical suspicion, based on compatible symptoms and history of travel to a risk zone. […] Additional examinations consist of: Patient undergoing a lumbar puncture […] Lumbar puncture to analyse the cerebrospinal fluid, which tends to show signs of inflammation. […] Blood analysis to detect specific antibodies against the virus.
  • #7 Prevention, diagnosis, and management of Japanese encephalitis in chil | PHMT
    https://www.dovepress.com/prevention-diagnosis-and-management-of-japanese-encephalitis-in-childr-peer-reviewed-fulltext-article-PHMT
    Attempts at isolating the virus from blood are mostly unsuccessful due to the very short period of viremia. […] Detection of JEV genome by reverse transcriptase polymerase chain reaction techniques is being employed in the diagnosis of JE. […] Blood (serum) and CSF specimens should be collected for JE diagnosis. […] All attempts should be made to collect CSF samples for confirmation of diagnosis. […] WHO case definition […] Clinically, AES is defined as: a person of any age, at any time of year with acute onset of fever and at least one of; a) change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk); b) new onset of seizures (excluding simple febrile seizures). […] The WHO has laid down criteria for laboratory confirmation of JE.
  • #7 Prevention, diagnosis, and management of Japanese encephalitis in chil | PHMT
    https://www.dovepress.com/prevention-diagnosis-and-management-of-japanese-encephalitis-in-childr-peer-reviewed-fulltext-article-PHMT
    Japanese encephalitis is the single largest cause of viral encephalitis in the world today. […] The mainstay of laboratory diagnosis is the antibody capture enzyme-linked immunosorbent assay technique in cerebrospinal fluid. […] A clinical diagnosis of JE is usually made on the basis of clinical features consistent with encephalitis occurring in the context of an epidemic or outbreak in rural areas in monsoon and post-monsoon season in an endemic area. […] Serological tests for JE include the neutralization test, agar gel diffusion test, single radial hemolysis, complement fixation test, and the hemagglutination inhibition test. […] The mainstay for diagnosis now is the Immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay test in CSF or serum. […] Detection of IgM in CSF is about 70% in the first week and about 95% after 10 days from onset of illness.
  • #8 Japanese encephalitis (JE): Sign and Symptoms, Causes, Risk factors, Diagnosis, Complications, Treatment and Prevention – MedicoInfo
    https://medicoinfo.org/japanese-encephalitis-je-sign-and-symptoms-causes-risk-factors-diagnosis-complications-treatment-and-prevention/
    Japanese Encephalitis (JE) is a serious viral disease that primarily affects the central nervous system (CNS). Accurate diagnosis is crucial for timely treatment and preventing complications. Diagnosis is typically made through a combination of clinical assessment, epidemiological context, laboratory investigations, and imaging studies. While laboratory investigations provide definitive confirmation, careful clinical evaluation remains the cornerstone of diagnosis in resource-limited settings. Timely identification and differentiation from other causes of encephalitis are essential for effective management, reducing mortality, and mitigating long-term complications. […] Diagnosis begins with clinical suspicion based on symptoms and the patients exposure history. Japanese encephalitis is endemic in parts of Southeast Asia, the Indian subcontinent, and the Western Pacific, with outbreaks peaking during monsoon and post-monsoon seasons. Patients with a history of living in or traveling to these regions, especially those near paddy fields or pig farms (reservoirs for JEV), are at increased risk.
  • #8 Japanese encephalitis (JE): Sign and Symptoms, Causes, Risk factors, Diagnosis, Complications, Treatment and Prevention – MedicoInfo
    https://medicoinfo.org/japanese-encephalitis-je-sign-and-symptoms-causes-risk-factors-diagnosis-complications-treatment-and-prevention/
    CSF analysis is a critical component of Japanese encephalitis diagnostics, offering direct evidence of CNS infection. Lumbar puncture reveals typical findings such as lymphocytic pleocytosis, elevated protein levels, and normal or slightly reduced glucose concentrations, differentiating JE from bacterial meningitis. Importantly, CSF samples are also analyzed using MAC-ELISA to detect JEV-specific IgM antibodies, providing definitive confirmation of CNS involvement. […] Imaging plays a supportive role in Japanese encephalitis. MRI is particularly useful, showing characteristic findings such as bilateral thalamic hyperintensities, often symmetrical, and sometimes involving the basal ganglia, midbrain, or hippocampus. In severe cases, hemorrhagic changes may be visible. CT scans may reveal hypodensities in similar regions or complications such as cerebral edema or hydrocephalus. Imaging findings combined with clinical and epidemiological data strongly suggest JE.
  • #8 Japanese encephalitis (JE): Sign and Symptoms, Causes, Risk factors, Diagnosis, Complications, Treatment and Prevention – MedicoInfo
    https://medicoinfo.org/japanese-encephalitis-je-sign-and-symptoms-causes-risk-factors-diagnosis-complications-treatment-and-prevention/
    Japanese encephalitis must be differentiated from other encephalitic and meningitic conditions. Viral encephalitis caused by HSV, West Nile virus, or dengue can mimic JE but have distinct features like rash or temporal lobe involvement (in HSV). Bacterial meningitis typically presents with marked neck stiffness, purulent CSF, and higher mortality without antibiotics. Non-infectious causes such as autoimmune encephalitis or metabolic disorders should also be considered.
  • #9 Japanese encephalitis – Wikipedia
    https://en.wikipedia.org/wiki/Japanese_encephalitis
    Japanese encephalitis is diagnosed by commercially available tests detecting JE virus-specific IgM antibodies in serum and/or cerebrospinal fluid, for example by IgM capture ELISA. […] JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. Patients with JE virus IgM antibodies should have confirmatory neutralizing antibody testing. […] Confirmatory testing in the US is available only at the CDC and a few specialized reference laboratories. In fatal cases, nucleic acid amplification and virus culture of autopsy tissues can be useful. Viral antigens can be shown in tissues by indirect fluorescent antibody staining.
  • #10 Diagnostic Testing | Japanese Encephalitis | CDC
    http://medbox.iiab.me/modules/en-cdc/www.cdc.gov/japaneseencephalitis/healthcareproviders/healthcareproviders-diagnostic.html
    Japanese encephalitis (JE) should be considered in a patient with evidence of a neurologic infection (e.g., meningitis, encephalitis, or acute flaccid paralysis) who has recently traveled to or resided in an endemic country in Asia or the western Pacific. […] Laboratory diagnosis of JE is generally accomplished by testing of serum or cerebrospinal fluid (CSF) to detect virus-specific IgM antibodies. JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. […] Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. For patients with JE virus IgM antibodies, confirmatory neutralizing antibody testing should be performed.
  • #10 Diagnostic Testing | Japanese Encephalitis | CDC
    http://medbox.iiab.me/modules/en-cdc/www.cdc.gov/japaneseencephalitis/healthcareproviders/healthcareproviders-diagnostic.html
    In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of autopsy tissues can also be useful. […] Diagnostic testing for JE virus IgM antibodies is commercially-available. Confirmatory testing is only available at CDC and a few specialized reference laboratories. Healthcare providers should contact their state or local health department or the CDC Arboviral Diseases Branch (telephone: 970-221-6400) for assistance with diagnostic testing.
  • #11 Indian Pediatrics – Editorial
    https://www.indianpediatrics.net/nov2001/nov-1252-1264.htm
    Japanese encephalitis virus infection results in nonspecific symptoms necessitating laboratory studies in an individual case. The diagnosis at the primary health center (PHC) level is based on clinical symptoms only. Therefore, there is a need to develop simple tests for use at the peripheral level both for diagnosis and for epidemiological surveys. The clinical suspicion of encephalitis can be supported with CSF analysis. A serology report requires more than a week and so this test is not useful immediately for the management of a critically ill patient. Serology, therefore, is useful only for retrospective confirmation of diagnosis and epidemic management. The recommended diagnostic method is IgM capture enzyme linked immunosorbent assay (ELISA). Specific IgM antibodies can be detected in CSF, serum or both in approximately 75% of the patients by the 3rd day of onset of disease and nearly all patients are positive 7 days after onset of the disease. Sero-confirmation is desirable in the initial phase of an outbreak and in sporadic cases. In outbreak situations, it is neither required nor is it feasible for laboratory to confirm all the cases. Only a representative number of samples to clinch the diagnosis is sufficient. CSF IgM antibodies detection is more reliable than IgM antibodies in serum for arriving at the diagnosis of JE, since antibodies in blood may not indicate CNS involvement. The sensitivity of CSF IgM is about 80-90% as compared to 10% of serum IgM. Detection of viral genome by polymerase chain reaction is easier to perform and highly reliable with 100% sensitivity but is expensive.
  • #12 Japanese Encephalitis Virus – Creative Diagnostics
    https://www.creative-diagnostics.com/Japanese-Encephalitis-Virus.htm
    Individuals who live in or have travelled to a JE-endemic area and experience encephalitis are considered a suspected JE case. […] To confirm JEV infection and to rule out other causes of encephalitis requires a laboratory testing of serum or, preferentially, cerebrospinal fluid. […] Laboratory diagnosis of JE is generally accomplished by testing of serum or cerebrospinal fluid (CSF) to detect virus-specific IgM antibodies. […] JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. […] Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. […] Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. […] For patients with JE virus IgM antibodies, confirmatory neutralizing antibody testing should be performed. […] In fatal cases, nucleic acid amplification, histopathology with immunohistochemistry, and virus culture of autopsy tissues can also be useful.
  • #13 Diagnostics in infectious encephalitis | Encephalitis International
    https://www.encephalitis.info/diagnosis-of-encephalitis/diagnostics-in-infectious-encephalitis/
    The diagnosis of infectious encephalitis aims to establish that there is inflammation within the brain, and secondly to find the cause of the inflammation. […] Although the identification of the pathogens causing encephalitis remains challenging, and in many cases the cause is still unknown, there have been many advances in the diagnosis of encephalitis over the past few years. […] Diagnostic tests used in encephalitis can be split into two broad categories: Laboratory tests, which analyse samples from patients such as cerebrospinal fluid, blood, urine and other body fluids. […] This is the vital test to establish a diagnosis of encephalitis. […] All patients suspected of encephalitis should have a lumbar puncture as soon as possible unless there is a clear reason preventing it from taking place.
  • #13 Diagnostics in infectious encephalitis | Encephalitis International
    https://www.encephalitis.info/diagnosis-of-encephalitis/diagnostics-in-infectious-encephalitis/
    Various laboratory tests are performed on CSF. […] Diagnosing encephalitis can be challenging and there is no single test which will give patients and doctors an answer. […] The diagnostic test can help to confirm a diagnosis when a direct cause is found (there is evidence the pathogen has caused the inflammation), can make a probable diagnosis (when all tests and clinical features suggest a cause and treatment seems to be efficient) or a diagnosis of encephalitis with an unknown cause. […] Some of these tests may be negative in the first few days after the onset of the illness. […] There are many factors which make establishing an encephalitis diagnosis challenging.
  • #14 Diagnosis of Japanese Encephalitis infection – GPnotebook
    https://gpnotebook.com/en-GB/pages/infectious-disease/japanese-b-encephalitis/diagnosis-of-japanese-encephalitis-infection
    Laboratory diagnosis of JEV infection includes: […] measurement of JEV-specific IgM can be carried out in CSF of most patients by 4 days after onset of symptoms and in serum by 7 days after onset […] in lumbar puncture CSF typically has a mild to moderate pleocytosis with a lymphocytic predominance […] slightly elevated protein […] normal ratio of CSF to plasma glucose.
  • #15
    https://journals.lww.com/pidj/fulltext/2015/12000/japanese_encephalitis_presenting_without.35.aspx
    Japanese encephalitis virus (JEV) is a neurotropic virus that predominately affects the thalamus, anterior horns of the spinal cord, cerebral cortex, and cerebellum and is one of the important causes of viral encephalitis in Southeast Asia. The diagnosis is made based on the epidemiologic clues along with lumbar puncture to confirm the diagnosis. The initial cerebrospinal fluid (CSF) analysis in JEV encephalitis shows lymphocytic pleocytosis, and the etiology is confirmed by CSF polymerase chain reaction (PCR), CSF JEV immunoglobulin M (IgM) or serum JEV IgM. […] We report 5 cases of JEV infection presenting with normal CSF findings but subsequently confirmed by PCR. […] These cases highlight that a high index of suspicion is required in endemic areas for the diagnosis of JE and the importance of JEV PCR in CSF, even if the initial CSF analysis shows the absence of pleocytosis. Although the treatment of JE is symptomatic, confirmatory diagnosis is important for prognosis, parenteral counseling and public health issues.
  • #16 Japanese encephalitis: a review of the Indian perspective | The Brazilian Journal of Infectious Diseases
    https://bjid.org.br/en-japanese-encephalitis-review-indian-perspective-articulo-S1413867012002073
    IgM capture enzyme-linked immunosorbent assay (ELISA) has been the most widely used diagnostic methods for JEV antibody detection. […] Real-time polymerase chain reaction (PCR) assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible.
  • #17 Detection of Japanese Encephalitis Virus RNA in Human Throat Samples in Laos – A Pilot study | Scientific Reports
    https://www.nature.com/articles/s41598-018-26333-4
    Japanese encephalitis virus (JEV) is the most commonly identified cause of acute encephalitis syndrome (AES) in Asia. The WHO recommended test is anti-JEV IgM-antibody-capture-enzyme-linked-immunosorbent-assay (JEV MAC-ELISA). However, data suggest this has low positive predictive value, with false positives related to other Flavivirus infections and vaccination. JEV RT-PCR in cerebrospinal fluid (CSF) and/or serum is highly specific, but is rarely positive; 0.25% of patients that fulfil the WHO definition of JE (clinical Acute Encephalitis Syndrome (AES) and JEV MAC-ELISA positive). Testing other body fluids by JEV RT-qPCR may improve the diagnosis. […] We suggest that testing patients throat swabs for JEV RNA is performed, in combination with molecular and serological CSF and serum investigations, on a larger scale to investigate the epidemiology of the presence of JEV in human throats. Throat swabs are an easy and non-invasive tool that could be rolled out to a wider population to improve knowledge of JEV molecular epidemiology.
  • #17 Detection of Japanese Encephalitis Virus RNA in Human Throat Samples in Laos – A Pilot study | Scientific Reports
    https://www.nature.com/articles/s41598-018-26333-4
    We provide strong evidence of JEV RNA detection in throat swab from two patients with clinical presentation of AES. […] Therefore, the use of throat swabs in addition to serum and CSF increased JEV molecular detection. In contrast to JEV MAC-ELISA, the detection of JEV RNA is highly specific for confirming JEV infection. Throat swabs are non-invasive samples, which may be useful to improve diagnosis, especially in patients in whom a lumbar puncture (LP) is not possible or where LP facilities are not available.
  • #18 Japanese Encephalitis Virus – Certest Biotec – Raw Materials | Diagnostics | Pharma
    https://www.certest.es/products/japanese-encephalitis-virus/
    VIASURE Japanese encephalitis virus Real Time PCR Detection Kit is designed for detection of Japanese encephalitis virus in blood or CSF from patients with signs and symptoms of Japanese encephalitis virus infection. […] This test is intended for use as an aid in the diagnosis of the Japanese encephalitis virus in combination with clinical and epidemiological risk factors. […] The diagnosis of Japanese encephalitis infection relies on the detection of specific IgM antibodies which are present in cerebrospinal fluid (CSF) and serum specimens from patients after 4-7 days post onset clinical symptoms. […] Viral direct detection by RT-PCR could be performed on blood or CSF in early stage of the disease and on cerebral biopsies from deceased patients.
  • #19 Japanese encephalitis: a review of the Indian perspective | The Brazilian Journal of Infectious Diseases
    https://www.bjid.org.br/en-japanese-encephalitis-review-indian-perspective-articulo-S1413867012002073
    IgM capture enzyme-linked immunosorbent assay (ELISA) has been the most widely used diagnostic methods for JEV antibody detection. […] Real-time polymerase chain reaction (PCR) assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible. […] Another study described and evaluated a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detecting JEV. The sensitivity of the JEV RT-LAMP assay was in concordance with that real-time RT-PCR, and it was more sensitive than that of conventional RT-PCR. The JEV RT-LAMP assay was highly specific; no cross-reactivity was found with dengue-2 virus, rabies virus, norovirus, astrovirus, and human enterovirus 71. The JEV RT-LAMP assay was simpler and less time-consuming compared to the conventional RT-PCR and real-time RT-PCR. The results suggest that the RT-LAMP assay can be applied as a practical molecular diagnostic tool for JEV infection and surveillance.
  • #20 How Is Japanese Encephalitis Diagnosed In A Clinical Setting? – Klarity Health Library
    https://my.klarity.health/how-is-japanese-encephalitis-diagnosed-in-a-clinical-setting/
    If a person does have japanese encephalitis virus, this testing will confirm if the person is positive for JEV antibodies and does in fact have the virus. […] A PCR test is also commonly done, using cerebral spinal fluid. This can identify if a sample is positive for DNA of the japanese encephalitis virus and subsequently determine if a person does have JEV or not. […] These types of molecular testing furthermore have the ability to accurately differentiate between viruses, for a specific and accurate diagnosis. […] Brain scans can be performed in order to support a laboratory diagnosis or a clinical examination diagnosis. […] Though these brain scans support laboratory investigations, they often are not able to differentiate between the flaviviruses that have caused the lesions. […] A combination of various factors including clinical information, laboratory findings and neuroimaging are all essential for the most accurate diagnosis.
  • #20 How Is Japanese Encephalitis Diagnosed In A Clinical Setting? – Klarity Health Library
    https://my.klarity.health/how-is-japanese-encephalitis-diagnosed-in-a-clinical-setting/
    While initial symptoms may be mild and non specific to the disease, more severe symptoms can prove more identifiable to the disease and ultimately help identify the disease. […] Although diagnostic methods, which include various laboratory tests, are both specific and accurate, vaccination remains the most effective way to prevent infection.
  • #21 MR Imaging in Biphasic Japanese Encephalitis | American Journal of Neuroradiology
    https://www.ajnr.org/content/29/3/e3
    Japanese encephalitis (JE) is usually a monophasic disease characterized by fever, altered sensorium with or without seizures, and other focal neurologic symptoms. […] MR imaging helps in establishing an early diagnosis and shows lesions in the thalami, substantia nigra, basal ganglia, hippocampi, cerebral cortex, brain stem, and cerebellum. […] CSF immunoglobulin capture enzyme-linked immunosorbent assay (MAC-ELISA) result was 250 U, establishing a diagnosis of JE. […] MR imaging shows fresh JE lesions in the second phase, in addition to JE lesions in the first. […] In conclusion, JE may rarely present as a biphasic illness. MR imaging shows typical JE lesions in the first phase, with fresh areas of involvement in the second phase.
  • #22 Japanese Encephalitis Virus antigens & antibodies – The Native Antigen Company
    https://thenativeantigencompany.com/japanese-encephalitis-virus/
    Diagnosis of JEV infection is achieved by serological testing for JEV specific IgM antibodies in the patients cerebrospinal fluid or serum. […] However, cross-reactivity of JEV specific antibodies with other Flaviviruses that co-circulate with JEV, such as Dengue virus, can be a challenge and can prevent accurate diagnosis.
  • #23 Investigation procedures for Japanese encephalitis (JE) in horses | Information for veterinarians and epidemiologists | Emergency animal diseases | Animal diseases | Biosecurity | Agriculture Victoria
    https://agriculture.vic.gov.au/biosecurity/animal-diseases/emergency-animal-diseases/investigation-procedures-for-japanese-encephalitis-je-in-horses
    Laboratory diagnosis for Japanese Encephalitis Virus (JEV) is achieved by serological tests. […] There is a high degree of serological cross-reactivity between flaviviruses, so care must be taken in interpreting results in areas where related flaviviruses co-circulate. […] Of the antibody tests available, the plaque-reduction neutralisation test (PRNT) is the most specific and may resolve cross-reactions. […] Molecular tests (reverse transcriptase-PCR) are available but have very low sensitivity. […] Infection with JEV can also be detected in fixed tissues using immunohistochemistry diagnosis. […] Japanese encephalitis is a notifiable disease throughout Australia. […] If SDI funding support is approved, PRNT testing at ACDP can occur following receipt of a complete set of samples (initial and convalescent serum samples).
  • #24 Japanese Encephalitis – Viral Diseases – Infectious Diseases – Diseases – McMaster Textbook of Internal Medicine
    https://empendium.com/mcmtextbook/chapter/B31.II.18.1.21.
    1. Identification of the etiologic agent: […] 1) Serologic studies: Detection of IgM antibodies in cerebrospinal fluid (CSF) or in serum (enzyme-linked immunosorbent assay [ELISA]). In most patients, JEV-specific IgM is detectable in CSF 4 days after symptom onset, and 7 days in serum (sensitivity 95% if 10 days after symptom onset). Because of the potential cross-reactions with antibodies against other flaviviruses (eg, dengue virus [DENV] or West Nile virus [WNV]), a plaque reduction neutralization test (PRNT) is performed: a 4-fold increase in the JEV-specific IgG titer detected through a PRNT in 2 serum samples collected 14 days apart (ie, acute and convalescent phases) confirms recent JEV infection. Past infection (ie, IgM may be persistently detectable for 30-90 days) or vaccination may also impact the interpretability of serologic studies. […] 2) Molecular studies (reverse transcriptasepolymerase chain reaction [RT-PCR], reverse transcription loop-mediated isothermal amplification [RT-LAMP]; material: CSF, blood, brain tissue) are not commonly used due to small viremic load in JE and sufficient diagnostic utility of serologic tests. […] 3) Detection of viral antigens in brain tissue (immunohistochemical or immunofluorescent method). […] 4) Virus isolation (by culture) from blood, CSF, or brain tissue (eg, in autopsy).
  • #25 Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits in: The American Journal of Tropical Medicine and Hygiene Volume 94 Issue 4 (2016)
    https://www.ajtmh.org/view/journals/tpmd/94/4/article-p820.xml
    The JEV MAC-ELISA is recommended by the World Health Organization (WHO) to diagnose acute JEV infections and has been used by the WHO Japanese encephalitis (JE) laboratory network since 2006 for laboratory-based surveillance of JE and other causes of AES/AMES. […] However, it was observed at the Centers for Disease Control and Prevention (CDC) that the DEN Detect kit had high specificity when JEV IgM+ samples were included. […] A JEV differential testing algorithm was developed in which samples tested by JE Detect with positive results were subsequently tested with the DEN Detect kit, and results of both tests used to make the final interpretation. […] The testing algorithm and final interpretations are illustrated in Figure 1. Briefly, all samples were tested first by the JE Detect. Samples with JEV+ results and those with JEV EQ results that remained EQ upon retesting were tested by DEN Detect.
  • #25 Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits in: The American Journal of Tropical Medicine and Hygiene Volume 94 Issue 4 (2016)
    https://www.ajtmh.org/view/journals/tpmd/94/4/article-p820.xml
    The 200 serum specimens were classified by reference laboratory testing as JE+ (N = 60) or JE (N = 140); reference DENV IgM+ (N = 24) and WNV IgM+ (N = 5) samples were included in the JE subset. […] The 75 CSF samples were classified by reference laboratories as JE+ (N = 24) and JE (N = 51), including nine CSF that had been confirmed as DENV IgM+ by PRNT at CDC, but which were not tested by the other reference laboratories for DENV IgM. […] The majority of serum specimens in the well-characterized reference panel were correctly identified by testing initially with the non-JE-specific JE Detect, then with the more specific DEN Detect. […] Although there are some common components, the dilution buffers are different and cannot be substituted for the other, they have been calibrated separately, and they have different cutoff values. […] The other eight CDC DENV IgM+ CSF with JEV results by JE Detect would not be tested by DEN Detect. However, to determine the sensitivity of DEN Detect for CSF samples, all the CDC DENV IgM+ CSF were tested by DEN Detect and all had negative results.
  • #26 Japanese Encephalitis Virus (JEV) Immunoassays – Creative Diagnostics
    https://www.creative-diagnostics.com/ivd-materials/support/japanese-encephalitis-virus-jev-immunoassays.html
    Rapid and accurate diagnosis of JEV infections aids clinicians in providing timely and appropriate medical interventions. […] Immunoassays play a crucial role in monitoring the prevalence of JEV in populations and geographic regions. […] Immunoassays are used to assess the immune response to JEV vaccines. […] In regions where JEV is endemic, screening blood donations for the presence of JEV-specific antibodies is essential to prevent the transmission of the virus through blood transfusions. […] Cross-reactivity with antibodies from related flaviviruses, especially Dengue virus, can lead to false-positive results. […] Achieving the right balance between sensitivity and specificity is crucial. […] Rapid ICTs provide a valuable solution in such settings, offering quick results without the need for specialized equipment. […] Immunoassays, with their versatility and applicability, play a pivotal role in the diagnosis and surveillance of JEV infections.
  • #27 Japanese encephalitis virus (JEV) infection for health professionals | Australian Centre for Disease Control
    https://www.cdc.gov.au/topics/JEV-infection-health-professionals
    JEV infection is usually diagnosed through laboratory testing of a sample of cerebrospinal fluid or blood to detect the JEV nucleic acid. A serum sample is necessary for serological diagnosis. […] Laboratories need extensive experience in diagnostic testing for flaviviruses, as cross-reactivity with other flaviviruses is common in serological tests. […] If JEV infection is part of a differential diagnosis, it’s important to specifically request JEV testing when referring patients to pathologists. […] There is no specific antiviral treatment for JEV infection. Clinical management consists of supportive care. […] People with suspected JEV infection are generally referred to hospital for management and further investigation.
  • #28 Japanese encephalitis virus
    https://www.health.vic.gov.au/infectious-diseases/japanese-encephalitis
    Most JE virus infections are asymptomatic. Less than one percent of people with JE virus infection develop clinical disease. […] Confirmation of JE is made by isolating or detecting the virus from a clinical sample or by a rising antibody titre in conjunction with compatible clinical evidence. […] The usual investigations for common causes of encephalitis or meningoencephalitis should be conducted concurrently, including CSF sampling if safe and appropriate. […] Recommended laboratory testing for JE includes all of the following: […] Collect acute and convalescent (2 to 4 weeks post symptom onset) serology samples. This is essential as antibodies may not be detectable at symptom onset. […] Cross reaction of antibodies to other flaviviruses is possible. […] Samples should be sent urgently to the Victorian Infectious Diseases Reference Laboratory (VIDRL) which performs testing for MVE virus and other flaviviruses in Victoria. […] JE vaccination is not part of the National Immunisation Program schedule.
  • #29 Submitting samples for Japanese encephalitis testing | Business Queensland
    https://www.business.qld.gov.au/industries/service-industries-professionals/service-industries/veterinary-surgeons/japanese-encephalitis/submitting-samples
    Submit samples from clinically consistent cases directly to the Biosecurity Sciences Laboratory (BSL), using these advice sheets: […] Laboratory testing of pigs and horses with signs consistent with clinical Japanese encephalitis (JE), where appropriate samples have been submitted, will be fully subsidised by the Queensland Government. […] Complete and suitable samples support a thorough diagnostic work-up and improves the likelihood of reliable and meaningful results. […] A confirmed diagnosis of JEV infection can be made through these methods: isolation and identification of JEV, detection of JEV by nucleic acid testing, seroconversion or a significant increase in JEV-specific antibody level by testing paired serum samples in a virus neutralisation test, detection of elevated levels of JEV-specific IgM antibody in CSF.
  • #30
    https://www.health.nsw.gov.au/Infectious/factsheets/Pages/japanese_encephalitis.aspx
    If you have the symptoms listed above a doctor may run a test to detect a virus or measure levels of antibodies to Japanese encephalitis in samples of blood or spinal fluid. […] There is no specific treatment for Japanese encephalitis. Patients with symptoms often need hospital support and sometimes intensive care. […] The Japanese encephalitis vaccine is safe and effective. People aged 2 months and older can get the vaccine. Vaccination against Japanese encephalitis is recommended for those at the highest risk of getting Japanese Encephalitis.