Etiologija lymske nevroborelioze pri otrocih v Sloveniji: vpliv vrste Borrelia burgdorferi sensu lato na klinično sliko

Rožič, Mojca (author), Arnež, Maja (mentor)

IZVLEČEK Uvod Lymska borelioza je zoonoza, ki jo povzročajo bakterije iz skupine Borrelia burgdorferi sensu lato. V Evropi se človek okuži z vbodom okuženega ščitastega klopa Ixodes ricinus. Če borelije v procesu razsoja po telesu vstopijo v živčni sistem, se razvije lymska nevroborelioza. Lymsko nevroboreliozo pri odraslih bolnikih v Evropi povzročajo predvsem B. garinii, nato še B. afzelii in B. burgdorferi. Dokazali so, da je klinična slika lymske nevroborelioze pri odraslih bolnikih odvisna od vrste B. burgdorferi sensu lato, ki jo povzroča. Za populacijo otrok pa so podatki o etiologiji lymske nevroborelioze v Evropi skopi in objavljeno je le malo podatkov o vplivu vrste B. burgdorferi sensu lato na klinično sliko lymske nevroborelioze pri otrocih. Hipoteza S pričujočo raziskavo smo želeli preveriti dve hipotezi. Prva hipoteza je: “V Sloveniji je pri otrocih, enako kot pri odraslih bolnikih, B. garinii najpogostejši povzročitelj lymske nevroborelioze.” Druga hipoteza je: “Vrsta B. burgdorferi sensu lato vpliva na klinično sliko lymske nevroborelioze pri otrocih.” Metode Raziskava je potekala v enem centru. Trajala je 17 let. V raziskavo smo vključili otroke mlajše od 15 let, ki so imeli prisotne klinične znake sumljive za lymsko nevroboreliozo ali potrjeno lymsko boreliozo, pri katerih smo osamili B. burgdorferi sensu lato iz likvorja in pri katerih smo s pomočjo elektroforeze v utripajočem električnem polju določili vrsto B. burgdorferi sensu lato. Bolnike smo razdelili v skupine glede na vrsto osamljene B. burgdorferi sensu lato. Med posameznimi skupinami smo nato primerjali demografske in klinične podatke. Izvedli smo tudi analizo strojnega učenja in med izbranimi spremenljivkami poiskali tisto z najvišjo oceno relativne pomembnosti za razvrstitev otrok z lymsko nevroboreliozo glede na vrsto B. burgdorferi sensu lato. Rezultati V času raziskave smo B. burgdorferi sensu lato iz likvorja osamili pri 153 otrocih. Pri 71/113 (62.8%) otrocih smo dokazali B. garinii in pri 42/113 (37.2%) otrocih B. afzelii. Več otrok je z lymsko nevroboreliozo zbolelo v času od maja do avgusta kot v času od septembra do aprila (69.0% vs. 31.0%, p=0.012). Otroci okuženi z B. garinii niso imeli pogosteje simptomov značilnih za okužbo osrednjega živčevja ali katerih koli drugih simptomov kot otroci okuženi z B. afzelii. Pri otrocih okuženih z B. garinii so, v primerjavi z otroki okuženimi z B. afzelii, kot prvi znak/simptom bolezni erythema migrans opazili redkeje (21.1% vs. 45.2%, padj=0.021) in tudi ob kliničnem pregledu smo pri njih multiple erythema migrans našli redkeje (18.3% vs. 45.2%, padj=0.036). Pri otrocih okuženih z B. garinii pa so, v primerjavi z otroki okuženimi z B. afzelii, kot prvi znak/simptom bolezni simptome značilne za meningitis opazili pogosteje (57.7% vs. 28.6%, padj=0.012) in tudi ob kliničnem pregledu so pri njih meningitisni znaki bili prisotni pogosteje (69.0% vs. 38.1%, padj=0.019). Otroci okuženi z B. garinii so v likvorju imeli pogosteje prisotno limfocitno predominanco (92.9% vs. 65.0%, padj=0.008) in pogosteje zvišan albuminski količnik likvor/serum (80.6% vs. 50.0%, padj=0.038), kot otroci okuženi z B. afzelii. Med skupinama bolnikov okuženih z B. garinii ali B. afzelii ni bilo statistično značilnih razlik v rezultatih krvnih preiskav, pogostnostjo prisotnosti specifičnih borelijskih protiteles v serumu ali likvorju, in tudi ne v pogostnosti intratekalne sinteze specifičnih borelijskih protiteles. Koncentracija limfocitov v likvorju je spremenljivka z najvišjo oceno relativne pomembnosti za razvrstitev otrok z lymsko nevroboreliozo, ki jo povzročata B. garinii ali B. afzelii. Sledita ji koncentracija albumina v likvorju in vrednost levkocitov v likvorju. Zaključki Lymsko nevroboreliozo pri otrocih v Sloveniji najpogosteje povzroča B. garinii, nato B. afzelii. Tako smo potrdili prvo hipotezo. Klinični znaki in simptomi lymske nevroborelioze pri otrocih, ki so okuženi z B. garinii, niso bolj značilni za okužbo osrednjega živčevja, kot pri otrocih okuženih z B. afzelii. Vnetje osrednjega živčevja pa je bolj izraženo pri otrocih, ki so okuženi z B. garinii, kot pri otrocih okuženih z B. afzelii. Tako vse najdbe skupaj kažejo na to, da je klinična slika lymske nevroborelioze pri otrocih odvisna od vrste B. burgdorferi sensu lato, ki jo povzroča. Tako smo potrdili drugo hipotezo.

• Language: Slovenian
• Keywords: Lymska nevroborelioza, otroci, klinična slika, B. garinii, B. afzelii
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2020
• PID: 20.500.12556/RUL-117534
• COBISS.SI-ID: 29134339
• Publication date in RUL: 15.07.2020

Secondary language

• Language: English
• Title: Etiology of Lyme neuroborreliosis in children in Slovenia: impact of Borrelia burgdorferi sensu lato species on clinical presentation

Abstract

ABSTRACT Background Lyme borreliosis is a zoonosis caused by bacteria from Borrelia burgdorferi sensu lato complex. In Europe, it is transmitted to humans by infected Ixodes ricinus ticks. During dissemination, when borreliae reach the nervous system, manifestations of Lyme neuroborreliosis develop. In adult European patients, Lyme neuroborreliosis is mainly caused by B. garinii, followed by B. afzelii, and B. burgdorferi. In adult patients, it has been corroborated that the clinical presentation of Lyme neuroborreliosis depends on B. burgdorferi sensu lato species. However, data on the etiology of Lyme neuroborreliosis in children in Europe is limited, with only scarce data about the influence of B. burgdorferi sensu lato species isolated from CSF on clinical presentation of Lyme neuroborreliosis in children. Hypothesis In the present study, we wanted to confirm two hypotheses. First, that B. garinii is the main cause of Lyme neuroborreliosis in children in Slovenia, as in adult patients, and second, that the clinical presentation of Lyme neuroborreliosis in children depends on the B. burgdorferi sensu lato species that caused it. Methods The study was mono-centric. During its 17-year period, it included children younger than 15 years with clinical presentation suggestive of Lyme neuroborreliosis or confirmed Lyme borreliosis, who had B. burgdorferi sensu lato isolated from CSF, and who had the species of B. burgdorferi sensu lato identified by pulsed-field gel electrophoresis. Demographic and medical data were compared for children infected with various B. burgdorferi sensu lato species. Machine learning analysis was performed to search through chosen variables for the variable with the highest relative importance score in order to classify children with Lyme neuroborreliosis caused by various B. burgdorferi sensu lato species. Results 153 children had Borrelia burgdorferi sensu lato isolated from CSF. In 71/113 (62.8%) B. garinii, and in 42/113 (37.2%) B. afzelii were identified. Most cases of Lyme neuroborreliosis in children occurred between May and August compared to the period from September to April (69.0% vs. 31.0%, p=0.012). Patients infected with B. garinii did not report symptoms suggestive of central nervous system involvement or any other symptoms more often than patients infected with B. afzelii. In children infected with B. garinii, erythema migrans was seen as the first sign/symptom less often (21.1% vs. 45.2%, padj=0.021) compared with children infected with B. afzelii and multiple erythema migrans were observed less often on clinical examination (18.3% vs. 45.2%, padj=0.036). However, children infected with B. garinii presented symptoms of meningitis as the first sign/symptom (57.7% vs. 28.6%, padj=0.012), had positive meningeal signs on clinical examination (69.0% vs. 38.1%, padj=0.019), had CSF lymphocytic predominance (92.9% vs. 65.0%, padj=0.008 ), and had elevated albumin CSF/serum quotient (80.6% vs. 50.0%, padj=0.038) more often than children infected with B. afzelii. There were no statistically significant differences in laboratory blood findings, in the presence of specific borrelial antibodies in serum and CSF, and in intrathecal specific borrelial antibody production between groups of patients infected with B. garinii and B. afzelii. The variable with the highest relative importance score for classification between groups of children with Lyme neuroborreliosis caused by B. garinii and B. afzelii is CSF lymphocyte concentration, followed by CSF albumin level, and CSF white blood cell count. Conclusions In Slovenia, Lyme neuroborreliosis in children is more often caused by B. garinii, followed by B. afzelii. This confirms our first hypothesis. Signs and symptoms of Lyme neuroborreliosis in children caused by B. garinii are not more often suggestive of CNS involvement, but CNS inflammation is more pronounced in children infected with B. garinii, compared with children infected with B. afzelii. Thus, the whole clinical presentation of Lyme neuroborreliosis in children depends on B. burgdorferi sensu lato species. This confirms our second hypothesis.

• Keywords: Lyme neuroborreliosis, children, clinical findings, B. garinii, B. afzelii