Borelioza mózgu przenoszona przez kleszcze
Diagnostyka i diagnoza
Diagnostyka kleszczowego zapalenia mózgu (KZM) opiera się przede wszystkim na wykrywaniu swoistych przeciwciał IgM i IgG przeciwko wirusowi KZM (TBEV) w surowicy i/lub płynie mózgowo-rdzeniowym (PMR) za pomocą testu ELISA. Przeciwciała IgM pojawiają się zwykle w ciągu pierwszych 6 dni od początku objawów i są wykrywalne u prawie wszystkich hospitalizowanych pacjentów, jednak mogą utrzymywać się do 10 miesięcy u osób zaszczepionych lub po przebyciu infekcji. W PMR swoiste przeciwciała IgM stają się wykrywalne do 10 dnia choroby, a badanie PMR typowo wykazuje pleocytozę limfocytarną (≥5 x 10^6 komórek/L) oraz zwiększony stosunek albumin, wskazujący na uszkodzenie bariery krew-mózg. Diagnostyka molekularna metodą RT-PCR ma ograniczoną czułość ze względu na krótki okres wiremii, ale jest szczególnie przydatna u pacjentów z zaburzeniami odporności humoralnej oraz we wczesnej fazie gorączkowej KZM. Ze względu na możliwe reakcje krzyżowe przeciwciał IgG z innymi flawiwirusami, w diagnostyce różnicowej stosuje się testy neutralizacyjne, zwłaszcza u pacjentów wcześniej szczepionych przeciwko innym flawiwirusom (np. żółtej gorączce, japońskiemu zapaleniu mózgu, dengie).
Diagnostyka kleszczowego zapalenia mózgu (borelioza mózgu przenoszona przez kleszcze)
Diagnostyka kleszczowego zapalenia mózgu (KZM) stanowi istotne wyzwanie kliniczne ze względu na niespecyficzne objawy kliniczne tej choroby. Ponieważ KZM może manifestować się szerokim spektrum objawów, od łagodnych objawów grypopodobnych do ciężkiego zapalenia mózgu, prawidłowa diagnoza laboratoryjna jest kluczowa dla potwierdzenia zakażenia wirusem KZM (TBEV).12
Metody serologiczne jako podstawa diagnostyki
Diagnostyka serologiczna stanowi podstawową metodę rozpoznawania kleszczowego zapalenia mózgu. Polega ona głównie na wykrywaniu swoistych przeciwciał przeciwko wirusowi KZM w surowicy i/lub płynie mózgowo-rdzeniowym pacjenta.12
Najczęściej stosowaną metodą diagnostyczną jest test immunoenzymatyczny ELISA, służący do wykrywania przeciwciał klasy IgM i IgG skierowanych przeciwko wirusowi KZM. Przeciwciała IgM pojawiają się w ciągu pierwszych 6 dni od początku objawów i są zazwyczaj wykrywalne, gdy pojawiają się objawy neurologiczne.12 U prawie wszystkich pacjentów hospitalizowanych z powodu KZM przeciwciała te są wykrywalne w momencie przyjęcia do szpitala.1
Należy pamiętać, że swoiste przeciwciała IgM mogą utrzymywać się w organizmie nawet do 10 miesięcy u osób szczepionych lub tych, które przebyły naturalne zakażenie. Co więcej, przeciwciała IgG mogą wykazywać reakcje krzyżowe z innymi flawiwirusami.12
Diagnostyka płynu mózgowo-rdzeniowego
Punkcja lędźwiowa i badanie płynu mózgowo-rdzeniowego (PMR) są niezbędne w diagnostyce KZM.12 We wczesnej fazie choroby przeciwciała swoiste w PMR można wykryć tylko u około 50% pacjentów, ale do 10 dnia choroby stają się one prawie niezmiennie wykrywalne.1
Badanie PMR wykazuje zazwyczaj pleocytozę limfocytarną, jednak w pierwszych dniach fazy neuroinfekcji w płynie mózgowo-rdzeniowym mogą przeważać neutrofile.1 Obserwuje się również zwiększony stosunek albumin, co wskazuje na uszkodzenie bariery krew-mózg, charakterystyczne dla zapalenia opon mózgowo-rdzeniowych.1
Wykrycie przeciwciał IgG w PMR nie wskazuje przede wszystkim na ostre zakażenie TBEV. Natomiast wykrycie IgM w PMR może pomóc w odróżnieniu ostrego zakażenia TBEV od odpowiedzi przeciwciał wywołanej niedawnym szczepieniem.1
Diagnostyka molekularna
Izolacja wirusa lub wykrycie wirusowego RNA metodą reakcji łańcuchowej polimerazy z odwrotną transkrypcją (RT-PCR) w PMR lub surowicy może również służyć do diagnozowania KZM, ale testy te rzadko dają wynik pozytywny w rutynowej diagnostyce.12
Wirus może być wykryty we krwi podczas pierwszej fazy gorączkowej KZM, a także w tkance mózgowej (jeśli jest dostępna) podczas fazy obejmującej objawy ze strony ośrodkowego układu nerwowego.1 RT-PCR ma szczególne znaczenie w diagnostyce u pacjentów z zaburzeniami odporności, którzy mogą wymagać tych testów do rozpoznania choroby.1
Obecna technologia z wyboru do wykrywania TBEV to PCR, dostępna w kilku formatach. W przypadkach śmiertelnych wirus można wyizolować lub wykryć metodą RT-PCR z mózgu i innych narządów.12
Testy neutralizacji i potwierdzenie diagnozy
Z uwagi na możliwość reakcji krzyżowych z innymi flawiwirusami, szczególnie w przypadku przeciwciał IgG, do potwierdzenia diagnozy KZM stosuje się testy neutralizacyjne przeciwciał swoistych dla wirusa KZM.12
W przypadkach, gdy pacjent był wcześniej szczepiony przeciwko żółtej gorączce lub japońskiemu zapaleniu mózgu, bądź przebył infekcję wirusem dengi, wykonanie testu neutralizacji jest niezbędne do oceny odporności z powodu interferencji przeciwciał krzyżowo reagujących z flawiwirusami w testach ELISA i teście hamowania hemaglutynacji (HI).1
Kryteria diagnostyczne i problemy diagnostyczne
Według definicji Europejskiego Centrum Zapobiegania i Kontroli Chorób (ECDC), potwierdzony przypadek KZM wymaga zarówno objawów klinicznych KZM, jak i obecności przeciwciał IgM i IgG w surowicy lub IgM w PMR, lub IgM i IgG w PMR, lub wykrycia kwasu nukleinowego wirusa KZM w materiale klinicznym.1
Diagnostyka KZM może być trudna ze względu na niespecyficzne objawy kliniczne, które nie mogą być odróżnione od innych form wirusowego zapalenia mózgu czy innych chorób. Ostateczne potwierdzenie diagnozy KZM wymaga potwierdzenia zakażenia TBEV poprzez wykrycie wirusa lub wykazanie obecności swoistych przeciwciał w surowicy i/lub płynie mózgowo-rdzeniowym.1
Warto zauważyć, że badania obrazowe mózgu, takie jak tomografia komputerowa (TK) czy rezonans magnetyczny (MRI), mogą wykazać zmiany charakterystyczne dla zapalenia mózgu, ale nie mają specyficznych cech dla KZM i służą głównie do wykluczenia innych przyczyn objawów neurologicznych.12
Przypadki szczególne i wyzwania diagnostyczne
Pacjenci z niedoborami odporności
U pacjentów z zaburzeniami odporności humoralnej, takimi jak wcześniejsze leczenie przeciwciałami deplecyjnymi limfocyty B (np. rytuksymab), diagnostyka serologiczna może być zawodna. W tych przypadkach konieczne jest włączenie badania PCR TBEV do podejścia diagnostycznego.1
Przypadki zaszczepione
Diagnostyka KZM u osób wcześniej zaszczepionych przeciwko temu wirusowi stanowi szczególne wyzwanie. W Austrii, gdzie rocznie przeprowadza się 200 000–300 000 szczepień pierwotnych przeciwko KZM, przeciwciała IgM mogą utrzymywać się u szczepionych nawet przez 8 miesięcy, co może powodować problemy diagnostyczne.1
Zauważono wysoki odsetek wyników fałszywie dodatnich (57%) wśród zgłoszonych przypadków zaszczepionych, co sugeruje, że niektóre niezweryfikowane przypadki zaszczepione mogły być fałszywie dodatnie.1
Badania u dzieci
KZM należy podejrzewać u narażonych dzieci, które rozwijają wysoką gorączkę i ból głowy w okresie od kwietnia do listopada. Uzyskanie historii podróży dziecka do obszarów endemicznych jest ważne, a brak znanego ukąszenia kleszcza i brak objawów neurologicznych nie wykluczają tego schorzenia. KZM diagnozuje się za pomocą punkcji lędźwiowej i badań przeciwciał w surowicy.1
Algorytm postępowania diagnostycznego
Algorytm diagnostyczny KZM powinien obejmować następujące elementy:
- Rozpoznanie kliniczne oparte na objawach zapalenia ośrodkowego układu nerwowego oraz wywiadzie epidemiologicznym (pobyt na terenie endemicznym, ukąszenie kleszcza, spożycie niepasteryzowanego mleka)
- Badania laboratoryjne krwi, które mogą wykazać leukopenię i/lub trombocytopenię w pierwszej fazie choroby oraz nieprawidłowe wyniki testów wątrobowych
- Punkcja lędźwiowa i badanie PMR wykazujące pleocytozę (≥5 x 10^6 komórek/L)
- Badania serologiczne na obecność przeciwciał IgM i IgG przeciwko wirusowi KZM w surowicy i/lub PMR
- W przypadkach wątpliwych – potwierdzenie metodą RT-PCR lub testem neutralizacji
W przypadku podejrzenia KZM, lekarz prowadzący powinien skontaktować się z laboratorium referencyjnym w celu omówienia przypadku i zapewnienia, że odpowiednie próbki zostaną przesłane do badania.1
Wyzwania w diagnostyce i niedobadanie KZM
Badania wskazują, że pacjenci z typowymi objawami KZM są prawdopodobnie niedostatecznie badani, co prowadzi do niedodiagnozowania KZM w wielu krajach. Aby zapewnić odpowiednią identyfikację przypadków, testy na KZM powinny być bardziej konsekwentnie włączane do rutynowej praktyki dla wszystkich pacjentów, którzy zgłaszają się z odpowiednimi objawami i osób narażonych na typowe czynniki ryzyka, zwłaszcza ukąszenia kleszczy.1
Niedostateczne badanie i diagnozowanie KZM wpływa na nadzór nad tą chorobą, co wiąże się z niską świadomością i niedostatecznym badaniem, prowadząc do błędnego koła ciągłego niedodiagnozowania przypadków KZM.1
Podsumowanie diagnostyki KZM
Diagnoza kleszczowego zapalenia mózgu opiera się przede wszystkim na wykryciu swoistych przeciwciał przeciwko wirusowi KZM w surowicy i/lub płynie mózgowo-rdzeniowym pacjenta. Test ELISA jest główną metodą diagnostyczną, wykrywającą przeciwciała klasy IgM i IgG. Ze względu na możliwość reakcji krzyżowych z innymi flawiwirusami, w niektórych przypadkach konieczne jest przeprowadzenie testów neutralizacji.123
Wykrycie genomu wirusa metodą RT-PCR może być przydatne we wczesnej fazie choroby lub u pacjentów z niedoborami odporności, ale znaczenie kliniczne tej metody jest ograniczone ze względu na krótki okres wiremii.12
Diagnostyka KZM stanowi wyzwanie ze względu na niespecyficzny obraz kliniczny, podobny do innych neuroinfekcji. Prawidłowa diagnoza wymaga połączenia oceny objawów klinicznych, badań płynu mózgowo-rdzeniowego oraz testów serologicznych.12
Należy pamiętać, że wczesna i precyzyjna diagnostyka KZM jest kluczowa dla prawidłowego postępowania z pacjentem, mimo braku swoistego leczenia przeciwwirusowego dla tej choroby.12
Kolejne rozdziały
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Materiały źródłowe
- #1 Chapter 10: Diagnosis – TBE Bookhttps://tbenews.com/tbe/tbe10/
TBE appears with non-characteristic clinical symptoms, which cannot be distinguished from other forms of viral encephalitis or other diseases. […] Cerebrospinal fluid and neuro-imaging may give some evidence of TBE, but ultimately cannot confirm the diagnosis. […] Thus, proving the diagnosis TBE necessarily requires confirmation of TBEV-infection by detection of the virus or by demonstration of specific antibodies from serum and/or cerebrospinal fluid. […] During the phase of clinic symptoms from the CNS, the TBEV can only rarely be detected in the cerebrospinal fluid of patients. […] Most routinely used serological tests for diagnosing TBE (ELISA, HI, IFA) show cross reactions resulting from either infection with other flaviviruses or with other flavivirus vaccines. […] Due to the lack of specific symptoms, a definitive confirmation of the diagnosis requires taking the history of the patient with regard to a possible tick bite or ingestion of unpasteurized milk in a known or suspected endemic area, plus a positive result from a classical virological test that confirms TBEV-infection either directly by the detection of virus or indirectly via detection of specific anti-virus antibodies.
- #1 Clinical Testing and Diagnosis for Tick-borne Encephalitis | Tick-borne Encephalitis Virus | CDChttps://www.cdc.gov/tick-borne-encephalitis/hcp/diagnosis-testing/index.html
Serologic testing is the primary method for diagnosing tick-borne encephalitis (TBE). […] TBE virus-specific neutralizing antibody testing can be performed at CDC to confirm TBE. […] In the United States, diagnostic testing for TBE can be performed at CDC. Evidence of recent infection is typically based on detection of specific immunoglobulin (Ig) M in serum or cerebrospinal fluid (CSF). […] Therefore, testing for TBE virus-specific neutralizing antibodies is used to confirm a positive IgM result to diagnose TBE. […] Virus isolation or detection of viral RNA by reverse transcription-polymerase chain reaction (RT-PCR) in CSF or serum can also be used to diagnose TBE, but these are rarely positive. […] Patients who are immunocompromised might require these tests for diagnosis. […] To submit specimens for testing, please contact your state or local health department. They can assist you with determining if samples should be sent to the CDC Arbovirus Diagnostic Laboratory for further testing. Specimens should be submitted to CDC through state health departments. All results will be sent from CDC to the appropriate state health department.
- #1 Factsheet about tick-borne encephalitis (TBE)https://www.ecdc.europa.eu/en/tick-borne-encephalitis/facts/factsheet
The diagnosis of TBE is based on the detection of specific IgM antibodies in cerebrospinal fluid (intrathecal production) and/or serum, mainly by ELISA. TBE antibodies appear 06 days after onset and are usually detected when neurological symptoms are present. Specific IgM antibodies can persist for up to 10 months in vaccinees or individuals who acquired the infection naturally; IgG antibody cross-reaction is possibly observed with other flaviviruses. Detection by PCR methods could be valuable for an early differential diagnosis of TBE.
- #1 Diagnosis of tick-borne encephalitis – PubMedhttps://pubmed.ncbi.nlm.nih.gov/12628812/
The actual diagnosis of a tick-borne encephalitis (TBE) must be established in the laboratory because of the non-specific clinical features it presents. The method of choice is the demonstration of specific IgM- and IgG-serum antibodies by enzyme-linked immuno-sorbent assay (ELISA), since these antibodies are detectable in practically every case at the time of hospitalization. […] Early after onset of disease in the cerebrospinal fluid specific antibodies can only be found in 50% of the patients, but by the 10th day of illness they almost invariably become detectable. […] Virus isolation from the blood, or the detection of specific nucleic acid in the blood or the cerebrospinal fluid by reverse-transcriptase polymerase chain reaction (RT-PCR) usually is only successful during the first viremic phase of the disease before seroconversion.
- #1 Tick-borne encephalitis in children | Tidsskrift for Den norske legeforeninghttps://tidsskriftet.no/en/2023/09/clinical-review/tick-borne-encephalitis-children
The incidence of tick-borne encephalitis in Norway is increasing. […] Only a small number of cases of tick-borne encephalitis in children have been reported in Norway, and the condition may be underdiagnosed. […] The purpose of this article is to raise awareness and the level of knowledge about TBE in children. […] Recommended diagnostic criteria for a confirmed case of TBE are given in Box 1. In addition to clinical symptoms of infection in the central nervous system, inflammatory markers are usually present in the serum. […] A lumbar puncture is needed to make the diagnosis. […] Detection of antibodies in the serum is the cornerstone of microbiological diagnostics. […] The TBE virus RNA can be detected by PCR examination in blood during the initial phase of the illness, but the test has low sensitivity and is not routinely performed in spinal fluid.
- #1 Tick-Borne Encephalitis | IntechOpenhttps://www.intechopen.com/chapters/54912
In the second (meningoencphalitic) phase, platelet count is normal, whereas peripheral blood leukocyte count is normal or mildly elevated (rarely 15 109/L). […] A typical finding is lymphocytic pleocytosis; however, in the first few days of the meningoencephalitic phase of TBE, neutrophils may predominate in CSF. […] In the routine clinical practice, demonstration of antibodies to TBEV in serum (and in some cases also in CSF) by enzyme-linked immunosorbent assay (ELISA) is a standard microbiologic diagnostic approach with a high sensitivity and specificity. […] At the beginning of the meningoencephalitic phase, when patients are usually seen by their physicians and admitted to hospital, the large majority had specific serum IgM and IgG antibodies. […] In rare cases when only IgM antibodies to TBEV are found in the first serum sample, second sampling 12 weeks later reveals IgG seroconversion and enables a reliable diagnosis of (recent) TBEV infection. […] Knowledge in the understanding of TBE serology is required also in patients with meningitis or meningoencephalitis or who had been previously vaccinated against TBE.
- #1 Case Report: Tick-borne Encephalitis Virus Infection in Beneficiaries of the U.S. Military Healthcare System in Southern Germany | Health.milhttps://staging-mobile.health.mil/sitecore/content/MHSHome/News/Articles/2019/11/01/Tick-borne-Encephalitis-Virus-Infection?type=All&page=11
The patient was diagnosed with TBE on the basis of the compatible clinical presentation and positive serum TBE IgG and IgM antibodies. […] He was diagnosed with TBE based on his clinical presentation and positive serum TBE IgG and IgM antibodies. […] The patient’s CSF showed pleocytosis, leukocytosis, and an increased albumin ratio, indicative of a breakdown in the blood-brain barrier consistent with meningitis. […] The TBE IgG index is a diagnostic calculation that compares TBE IgG concentrations in the CSF to TBE IgG concentrations in the serum, controlling for total IgG concentrations in both the CSF and serum. […] The current report describes 3 cases of TBE that occurred among U.S. Military Health System beneficiaries living in Germany in 2017 and 2018. […] It is important for providers caring for military service members in Europe to be proficient in the recognition and treatment of TBE.
- #1 Chapter 10: Diagnosis – TBE Bookhttps://tbenews.com/tbe/tbe10/
The most common method of detecting TBEV infection nowadays is via serological assays, which have developed from complement fixation or hemagglutination inhibition tests through to modern immunoglobulin (Ig)-specific tests such as ELISAs and immunofluorescence (IF) assays. […] The current technology of choice for the detection of TBEV is PCR, and there are several formats available. […] However, TBEV can be detected in blood samples during the first febrile phase of TBE as well as in brain tissue (if available) during the phase involving CNS symptoms. […] Both IgM and IgG anti-TBEV antibodies can be detectable in CSF at the onset of CNS symptoms, and their detection can be important in special circumstances or for supporting the diagnosis of a TBEV infection. […] The detection of IgG in the CSF is therefore not primarily indicative of an acute TBEV infection. […] The detection of IgM in CSF may help to distinguish an acute TBEV infection from the antibody response induced by a recent vaccination. […] The degree of cross-reactions between different flavivirus antibodies is also dependent on the serological status of the patient resp. vaccinee.
- #1 Diagnosis of tick-borne encephalitis – PubMedhttps://pubmed.ncbi.nlm.nih.gov/12628812/
In fatal cases, the virus can be isolated or detected by RT-PCR from the brain and other organs. […] For testing immunity after a TBE virus infection or after vaccination, most often the IgG ELISA is used. However, in cases of other flavivirus contacts (e.g. vaccinations against yellow fever or Japanese encephalitis; dengue virus infections), the performance of a neutralization assay is necessary for assessing immunity due to the interference of flavivirus cross-reactive antibodies in ELISA and hemagglutination inhibition (HI) test.
- #1 Diagnosing tick-borne encephalitis: a re-evaluation of notified caseshttps://pmc.ncbi.nlm.nih.gov/articles/PMC5780526/
We set out to investigate the serological response of TBE virus (TBEV)-specific IgM and IgG antibodies in stored serum and cerebrospinal fluid (CSF) in notified TBE patients, in order to confirm or reject the diagnosis. […] The TBE diagnosis relies both on clinical and laboratory findings. The clinical picture is wide-ranging, making laboratory testing crucial. In almost all cases, IgM and often IgG in serum can be detected after onset of neurological symptoms. TBEV antibody testing in the cerebrospinal fluid (CSF) is considered a reliable diagnostic tool. […] According to the definitions of the European Center for Disease Control (ECDC) Meeting Report in 2011, a confirmed TBE case requires both clinical symptoms of TBE and IgM plus IgG in serum or IgM in the CSF or IgM plus IgG in the CSF or detection of TBE viral nucleic acid in clinical specimen.
- #1 Tick-Borne Encephalitishttps://www.encephalitis.info/types-of-encephalitis/infectious-encephalitis/tick-borne-encephalitis/
TBE can be diagnosed by a blood test and lumbar puncture (LP). LP (sometimes called a spinal tap) is a procedure which involves passing a needle, under local anaesthetic, between two of the backbones at the base of your spine to collect the cerebrospinal fluid (CSF) (fluid surrounding the brain and the spinal cord). […] The virus can be detected in the blood in the first phase of the illness, whilst the antibodies can be found in blood and cerebrospinal fluid, usually, in the second phase. Brain scans such as CT (computed tomography) and MRI (magnetic resonance imaging) can show abnormalities specific encephalitis, but do not have specific characteristics for TBE.
- #1 Results of Tick-Borne Encephalitis Virus (TBEV) Diagnostics in an Endemic Area in Southern Germany, 2007 to 2022https://www.mdpi.com/1999-4915/15/12/2357
In contrast, in 2 of 126 (1.6%) patients TBEV-specific IgM and IgG antibodies were completely negative and TBE was diagnosed by the detection of TBEV RNA in CSF. […] The performance of the TBEV IgM assay was evaluated for the confirmation or exclusion of TBE in patients with suspected CNS infection. […] Overall, the sensitivity and specificity of the TBEV IgM assays were 96.8% and 99.7%, respectively. […] In our analysis, the highest TBEV IgG seroprevalence of up to 68% was found in adolescents and young adults between 10 and 29 years, while the seroprevalence was markedly reduced to 45% in adults above 29 years. […] TBEV real-time PCR from CSF has no additional diagnostic value in immunocompetent patients but is necessary for the diagnosis of TBE in patients with humoral immunodeficiency such as a previous treatment with B cell-depleting antibodies like rituximab.
- #1 Laboratory diagnosis of tick-borne encephalitis | SpringerLinkhttps://link.springer.com/chapter/10.1007/978-3-7091-9091-3_18
As isolation of tick-borne encephalitis (TBE) virus is successful only from blood in the first, nonspecific phase of disease or from autopsy material, laboratory diagnosis is done usually by serological means. Classical serologic tests have been replaced by ELISA for detecting IgM antibodies to TBE virus. […] In Austria between 200,000 and 300,000 primary TBE vaccinations are performed each year. This may cause diagnostic problems because IgM antibodies persist in the vaccinees for as long as 8 months. In such cases confirmatory diagnosis may require demonstrating locally formed antibodies in the brain. For that purpose a special anti- ELISA was developed.
- #1 Tick-borne encephalitis vaccine effectiveness and barriers to vaccination in Germany | Scientific Reportshttps://www.nature.com/articles/s41598-022-15447-5
Notably, serum diagnostics are challenging in previously TBE vaccinated TBE cases due to unspecific antibody rises and cross-reactivity. German routine surveillance therefore stipulates validating vaccinated cases (1 dose) at the national reference laboratory with the NS1-antibody test to distinguish between true VBIs and false positives. […] The high false positive rate of 57% among notified vaccinated cases suggests that some of the unvalidated vaccinated cases may have been falsely positive.
- #1 Tick-borne encephalitis in children | Tidsskrift for Den norske legeforeninghttps://tidsskriftet.no/en/2023/09/clinical-review/tick-borne-encephalitis-children
Microbiological diagnostics are indicated in order to rule out differential diagnoses requiring treatment, such as herpes virus and varicella encephalitis, neuroborreliosis and bacterial meningitis. […] Diagnostic imaging such as MRI or CT scans are most beneficial in cases of acute and severe symptoms, primarily to rule out differential diagnoses that may require urgent treatment, for example intracranial bleeding, infarction or abscess. […] TBE should be suspected in exposed children who develop a high fever and headache in the period from April to November. Obtaining the child’s travel history to endemic areas is important, and the absence of a known tick bite and neurological findings do not rule out the condition. TBE is diagnosed via a lumbar puncture and antibody testing in the serum.
- #1 Tick-Borne Encephalitis | IntechOpenhttps://www.intechopen.com/chapters/54912
Tick-borne encephalitis (TBE) is an important central nervous system infection in Europe and Asia. […] TBE is delineated by three criteria: the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis; cerebrospinal fluid pleocytosis (5 106 cells/L); and demonstration of a recent infection with TBEV by the presence of specific serum IgM and IgG antibodies or IgG seroconversion. […] For a diagnosis of TBE, three criteria should be fulfilled: symptoms/signs indicating meningitis or meningoencephalitis, elevated CSF cell count (5 106 leukocytes/L), and microbiologic evidence of TBEV infection (i.e., the presence of specific IgM and IgG antibodies). […] In the initial (viremic) phase of TBE leukopenia and/or thrombocytopenia are ascertained in around 70% of patients, and abnormal liver test results are seen in about 20%.
- #1https://www.gov.uk/guidance/tick-borne-encephalitis-epidemiology-diagnosis-and-prevention
Testing is done by the UKHSA Rare and imported pathogens laboratory (RIPL). If TBE is suspected, the referring clinician should contact a clinician at RIPL to discuss the case to ensure that the correct samples are sent for testing. […] TBEV is a notifiable organism, and you should notify your local health protection team if detected. […] In July 2019, a European visitor became ill after being bitten by a tick in the New Forest area. This was considered to be a highly probable case of tick-borne encephalitis, based on serological testing. […] In July 2020, a second probable case of TBE infection was diagnosed in a patient from Hampshire, again based on serological testing. […] In September 2022, a third case, confirmed positive by polymerase chain reaction (PCR), was diagnosed in an individual who is likely to have acquired infection in the Loch Earn area of Scotland. […] In October 2022, a fourth case, also confirmed positive by PCR, was diagnosed in an individual who reported recent exposure to ticks in the North Yorkshire Moors in England.
- #1 Evaluation of under-testing and under-diagnosis of tick-borne encephalitis in Germany | BMC Infectious Diseases | Full Texthttps://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08101-6
However, diagnosing TBE is difficult due to often non-specific symptoms. […] Findings from standard laboratory blood tests for patients presenting with non-specific symptoms during the first phase of TBE, such as leukopenia, thrombocytopenia or liver function tests, are not indicative of a TBE infection and therefore, an additional TBE-specific test is necessary to confirm a TBE case. […] In clinical practice, laboratory diagnosis usually depends on the detection of specific immunoglobulin M (IgM) in either blood or CSF during the second phase of the disease. […] Inadequate TBE testing and diagnosis impacts TBE surveillance, which is interlinked with low awareness and under-testing, leading to a vicious cycle of continued under-ascertainment of TBE cases. […] Findings suggest that patients with typical TBE symptoms are likely under-tested, indicating a potential under-diagnosis of TBE in Germany. To ensure appropriate case identification, TBE testing should be more consistently integrated into routine practice for all patients who present with relevant symptoms and those exposed to common risk factors, especially tick bite.
- #1 Results of Tick-Borne Encephalitis Virus (TBEV) Diagnostics in an Endemic Area in Southern Germany, 2007 to 2022https://www.mdpi.com/1999-4915/15/12/2357
Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted neurotropic flavivirus in Europe and Asia. Our analysis aimed to investigate the contribution of TBEV-specific antibody detection by serological assays and TBEV RNA detection by real-time PCR to the diagnosis of tick-borne encephalitis (TBE). […] TBEV-specific IgM ELISA tests showed a high clinical sensitivity (96.8%) and a very high clinical specificity (99.7%). In immunocompetent patients, TBE was reliably diagnosed by detection of TBEV IgM antibodies in serum. […] Therefore, in patients with CNS infection and humoral immunodeficiency, it is necessary to include TBEV PCR in the diagnostic approach. […] In total, 126 TBE cases were identified between 2007 and 2022 among 3713 patients from whom samples for TBEV diagnostics were submitted. In 124 of 126 (98.4%) patients TBE diagnosis was based on antibody detection.
- #1 TickAlert | Tick-borne encephalitis | Abouthttps://tickalert.org/tick-borne-encephalitis-about
If TBE is suspected, based on signs, symptoms and travel history, a blood or spinal fluid sample would be taken by a healthcare professional and sent for laboratory testing to detect TBE virus or another infection causing similar symptoms. […] If TBE is detected, it will be reported to Public Health England. […] There is no specific treatment for TBE, only supportive measures to treat the symptoms while your immune system fights off the virus and to help prevent complications. […] TBE has no cure but has the potential to cause serious and complicated consequences.
- #2 Diagnosis of tick-borne encephalitis – PubMedhttps://pubmed.ncbi.nlm.nih.gov/12628812/
The actual diagnosis of a tick-borne encephalitis (TBE) must be established in the laboratory because of the non-specific clinical features it presents. The method of choice is the demonstration of specific IgM- and IgG-serum antibodies by enzyme-linked immuno-sorbent assay (ELISA), since these antibodies are detectable in practically every case at the time of hospitalization. […] Early after onset of disease in the cerebrospinal fluid specific antibodies can only be found in 50% of the patients, but by the 10th day of illness they almost invariably become detectable. […] Virus isolation from the blood, or the detection of specific nucleic acid in the blood or the cerebrospinal fluid by reverse-transcriptase polymerase chain reaction (RT-PCR) usually is only successful during the first viremic phase of the disease before seroconversion.
- #2 Factsheet about tick-borne encephalitis (TBE)https://www.ecdc.europa.eu/en/tick-borne-encephalitis/facts/factsheet
The diagnosis of TBE is based on the detection of specific IgM antibodies in cerebrospinal fluid (intrathecal production) and/or serum, mainly by ELISA. TBE antibodies appear 06 days after onset and are usually detected when neurological symptoms are present. Specific IgM antibodies can persist for up to 10 months in vaccinees or individuals who acquired the infection naturally; IgG antibody cross-reaction is possibly observed with other flaviviruses. Detection by PCR methods could be valuable for an early differential diagnosis of TBE.
- #2 Tick-borne encephalitis (TBE) Serology and PCRâ Referred Out | Public Health Ontariohttps://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Tick-Borne-Encephalitis-Virus
This page provides information on the testing available for Tick-borne encephalitis (TBE), caused by the Tick-borne encephalitis virus (TBEV). Testing for TBE and the TBEV is not performed at PHOs laboratory and requests for serology and polymerase chain reaction (PCR) tests are referred to the National Microbiology Laboratory (NML) in Winnipeg. […] Testing is indicated for individuals with compatible clinical symptoms and exposure history. […] The diagnosis of TBE is based on the detection of specific IgM antibodies in cerebrospinal fluid (intrathecal production) and/or serum. TBE antibodies appear within 6 days after symptom onset and can be detected when neurological symptoms are present. […] Detection by PCR methods may be valuable for an early differential diagnosis of TBE. […] TBEV test requests are referred out to the National Microbiology Laboratory (NML) for testing.
- #2 Tick-borne encephalitis (TBE) Serology and PCRâ Referred Out | Santé publique Ontariohttps://www.publichealthontario.ca/fr/Laboratory-Services/Test-Information-Index/Tick-Borne-Encephalitis-Virus
This page provides information on the testing available for Tick-borne encephalitis (TBE), caused by the Tick-borne encephalitis virus (TBEV). Testing for TBE and the TBEV is not performed at PHOs laboratory and requests for serology and polymerase chain reaction (PCR) tests are referred to the National Microbiology Laboratory (NML) in Winnipeg. […] Testing is indicated for individuals with compatible clinical symptoms and exposure history. The diagnosis of TBE is based on the detection of specific IgM antibodies in cerebrospinal fluid (intrathecal production) and/or serum. TBE antibodies appear within 6 days after symptom onset and can be detected when neurological symptoms are present. Specific IgM antibodies can persist for up to 10 months in individuals who acquired the infection naturally.
- #2 Tick-Borne Encephalitishttps://www.encephalitis.info/types-of-encephalitis/infectious-encephalitis/tick-borne-encephalitis/
TBE can be diagnosed by a blood test and lumbar puncture (LP). LP (sometimes called a spinal tap) is a procedure which involves passing a needle, under local anaesthetic, between two of the backbones at the base of your spine to collect the cerebrospinal fluid (CSF) (fluid surrounding the brain and the spinal cord). […] The virus can be detected in the blood in the first phase of the illness, whilst the antibodies can be found in blood and cerebrospinal fluid, usually, in the second phase. Brain scans such as CT (computed tomography) and MRI (magnetic resonance imaging) can show abnormalities specific encephalitis, but do not have specific characteristics for TBE.
- #2 Diagnosis of tick-borne encephalitis – PubMedhttps://pubmed.ncbi.nlm.nih.gov/12628812/
In fatal cases, the virus can be isolated or detected by RT-PCR from the brain and other organs. […] For testing immunity after a TBE virus infection or after vaccination, most often the IgG ELISA is used. However, in cases of other flavivirus contacts (e.g. vaccinations against yellow fever or Japanese encephalitis; dengue virus infections), the performance of a neutralization assay is necessary for assessing immunity due to the interference of flavivirus cross-reactive antibodies in ELISA and hemagglutination inhibition (HI) test.
- #2 Tick-borne encephalitis virus – Swisstickshttps://swissticks.ch/en/pathogens/tick-borne-encephalitis-virus/
Tick-borne encephalitis (TBE) is a viral infection, which may affect the central nervous system. The disease may be fatal in some cases. A vaccine is available for protection against the disease. […] As the clinical symptoms and laboratory parameters generally do not differ from those of other central nervous system diseases, diagnosis has to be established with specific laboratory tests. In theory, direct detection of viral RNA is possible from blood samples taken during the first phase of the disease using polymerase chain reaction PCR. During the second phase, viral RNA is generally no longer detectable, neither in the blood nor in the cerebrospinal fluid, due to evolving immune response. […] Serology is the method of choice for detecting infections with TBEV. […] In the majority of patients with neurological symptoms, specific IgM and IgG antibodies are detectable in the first serum sample. Interpretation of serological tests is complicated by the pronounced cross-reactivity (especially for IgG antibodies) with other flaviviruses (e.g. Yellow Fever virus, Dengue virus, Japanese encephalitis virus; also upon vaccination against these viruses). Virus-binding but not neutralizing antibodies produce false-positive results in ELISA tests routinely used in diagnostic laboratories. Discrimination of virus-neutralizing antibodies requires a serum neutralization test; this test is performed at the CHUV, Laboratoire de Microbiologie.
- #2 Tick-borne encephalitis – Symptoms, diagnosis and treatment | BMJ Best Practicehttps://bestpractice.bmj.com/topics/en-gb/1613?q=Tick-borne%20encephalitis&c=suggested
Diagnosis is made based on immune status; seasonality; geographical, animal, and arthropod exposures; clinical findings; and radiographic abnormalities. TBE is a biphasic illness in most patients. […] Key diagnostic factors include presence of risk factors, fever, fatigue, general malaise, headache, body pains, nausea, mild meningitis, severe encephalitis, and altered mental state. […] Other diagnostic factors include cranial and spinal nerve palsies, vestibular/hearing defects, seizures, paresis, and arms, shoulders, and head muscles paralysis. […] 1st investigations to order include FBC, erythrocyte sedimentation rate, CRP, LFTs, CT brain, cerebrospinal fluid analysis, and cerebrospinal fluid/serum serology. […] Investigations to consider include cerebrospinal fluid/serum reverse-transcription polymerase chain reaction, MRI head, and EEG.
- #2 Tick-Borne Encephalitis | IntechOpenhttps://www.intechopen.com/chapters/54912
In the second (meningoencphalitic) phase, platelet count is normal, whereas peripheral blood leukocyte count is normal or mildly elevated (rarely 15 109/L). […] A typical finding is lymphocytic pleocytosis; however, in the first few days of the meningoencephalitic phase of TBE, neutrophils may predominate in CSF. […] In the routine clinical practice, demonstration of antibodies to TBEV in serum (and in some cases also in CSF) by enzyme-linked immunosorbent assay (ELISA) is a standard microbiologic diagnostic approach with a high sensitivity and specificity. […] At the beginning of the meningoencephalitic phase, when patients are usually seen by their physicians and admitted to hospital, the large majority had specific serum IgM and IgG antibodies. […] In rare cases when only IgM antibodies to TBEV are found in the first serum sample, second sampling 12 weeks later reveals IgG seroconversion and enables a reliable diagnosis of (recent) TBEV infection. […] Knowledge in the understanding of TBE serology is required also in patients with meningitis or meningoencephalitis or who had been previously vaccinated against TBE.
- #2 Results of Tick-Borne Encephalitis Virus (TBEV) Diagnostics in an Endemic Area in Southern Germany, 2007 to 2022https://www.mdpi.com/1999-4915/15/12/2357
In contrast, in 2 of 126 (1.6%) patients TBEV-specific IgM and IgG antibodies were completely negative and TBE was diagnosed by the detection of TBEV RNA in CSF. […] The performance of the TBEV IgM assay was evaluated for the confirmation or exclusion of TBE in patients with suspected CNS infection. […] Overall, the sensitivity and specificity of the TBEV IgM assays were 96.8% and 99.7%, respectively. […] In our analysis, the highest TBEV IgG seroprevalence of up to 68% was found in adolescents and young adults between 10 and 29 years, while the seroprevalence was markedly reduced to 45% in adults above 29 years. […] TBEV real-time PCR from CSF has no additional diagnostic value in immunocompetent patients but is necessary for the diagnosis of TBE in patients with humoral immunodeficiency such as a previous treatment with B cell-depleting antibodies like rituximab.
- #2 The TBE Book 7th Edition – TBE Bookhttps://tbenews.com/tbe/
TBE appears with non-characteristic clinical symptoms, which cannot be distinguished from other forms of viral meningitis encephalitis, or other diseases. […] Cerebrospinal fluid and neuro-imaging may give some evidence of TBE, but ultimately cannot confirm the diagnosis. […] Thus, proving the diagnosis TBE necessarily requires confirmation of TBEV infection by detection of the virus or by demonstration of specific antibodies from serum and/or cerebrospinal fluid.
- #2 What Is TBE | TicoVac⢠(Tick-Borne Encephalitis Vaccine) | Safety Infohttps://www.ticovac.com/travelers/whatistbe
Tick-borne encephalitis (TBE) is a rare viral infection of the brain and spine. Transmission of the TBE virus to humans most commonly occurs from the bite of an infected tick. Encephalitis means inflammation of the brain. […] There is no cure for TBE, and it cannot be treated with antibiotics or any other medication. […] For those suffering from severe disease, 30-60% may develop long-term consequences. […] Most people infected with the TBE virus have no symptoms. But if symptoms occur, they usually appear in two phases. In the initial phase, people experience flu-like symptoms. Some people experience the second phase, which can be serious with symptoms similar to other causes of inflammation of the brain and spine or meningitis.
- #3 Factsheet about tick-borne encephalitis (TBE)https://www.ecdc.europa.eu/en/tick-borne-encephalitis/facts/factsheet
The diagnosis of TBE is based on the detection of specific IgM antibodies in cerebrospinal fluid (intrathecal production) and/or serum, mainly by ELISA. TBE antibodies appear 06 days after onset and are usually detected when neurological symptoms are present. Specific IgM antibodies can persist for up to 10 months in vaccinees or individuals who acquired the infection naturally; IgG antibody cross-reaction is possibly observed with other flaviviruses. Detection by PCR methods could be valuable for an early differential diagnosis of TBE.