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Vpliv genotipa Mycoplasma pneumoniae na klinično sliko okužbe pri otrocih
ID Rodman Berlot, Jasna (Author), ID Keše, Darja (Mentor) More about this mentor... This link opens in a new window

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Abstract
Uvod in namen: Mycoplasma pneumoniae (Mp) je pogost povzročitelj okužb spodnjih dihal pri otrocih, a lahko povzroča tudi izvenpljučne okužbe. Dejavniki, ki določajo klinično sliko okužbe z Mp, so le deloma poznani. Seve Mp lahko glede na genski zapis za adhezin P1 razvrstimo v dve genetski skupini, imenovani P1 tip 1 (P1-1) in P1 tip 2 (P1-2). Večjo sposobnost razlikovanja sevov nam omogoča metoda multilokusne analize spremenljivega števila tandemskih ponovitev (angl. Multiple-Locus Variable number tandem repeat Analysis, MLVA). Vpliv genotipa Mp na klinično sliko okužbe pri otrocih še ni poznan. S preučevanjem kliničnih značilnosti bolnikov z znano okužbo z Mp smo želeli opredeliti, ali so genotipi Mp P1 in MLVA povezani s klinično sliko akutne okužbe pri otrocih. Metode: V retrospektivni klinični raziskavi smo pregledali zdravstveno dokumentacijo otrok, ki so bili od januarja do decembra 2014 obravnavani na Pediatrični kliniki, Univerzitetnem kliničnem centru Ljubljana (UKCL), in na Kliniki za infekcijske bolezni in vročinska stanja UKCL zaradi akutne okužbe z Mp. Vključitveni kriteriji za študijo so bili starost ? 18 let in dokazana navzočnost bakterije Mp v brisu žrela z molekularnim testom PCR. Izključitveni kriteriji so bili odsotnost znakov akutne okužbe in ugotovljeni drugi povzročitelj okužbe. Bolnike smo nato razvrstili glede na klinično sliko okužbe po organskih sistemih in glede na dokazan genotip Mp P1 in MLVA. Za posamezne klinične slike okužbe smo ocenili demografske, epidemiološke in klinične podatke ter porazdelitev genotipov Mp P1-1/-2 oziroma MLVA in jih statistično opredelili. Primerjali smo epidemiološke in klinične podatke pri pacientih z akutno okužbo spodnjih dihal z Mp genotipom P1-1 ali s P1-2 in znanimi genotipi MLVA. Primerjali smo epidemiološke in klinične podatke pacientov s kožno klinično sliko, okuženih z Mp P1-1 ali P1-2, ter med posameznimi genotipi MLVA. Izsledke smo primerjali s podatki kontrolne skupine otrok, ki niso imeli potrjene okužbe z Mp s testom PCR. Rezultati: Leta 2014 je bilo v naši bolnišnici napotenih 1621 otrok z znaki akutne okužbe z Mp. Glede na vključitvene in izključitvene kriterije smo v naši študiji pregledali podatke 482 bolnikov (260 (54 %) fantov in 222 deklic (46 %), povprečna starost 6,9 leta, standardna deviacija (SD) 3,4 leta). Najpogostejša klinična slika okužbe z Mp pri naših bolnikih je bila okužba spodnjih dihal, ki je bila prisotna pri 88 % bolnikov (425/482). Izvenpljučno klinično sliko okužbe je imelo 13 % (62/482) otrok, med katerimi je bila najpogostejša kožna, in sicer pri 9 % (45/482) otrok. V naši skupini bolnikov z mikoplazemsko okužbo nismo potrdili povezave genotipa Mp z določeno pljučno ali izvenpljučno klinično sliko. Primerjali smo podatke 310 bolnikov z okužbo spodnjih dihal z genotipom Mp P1-1 s podatki 110 bolnikov, okuženih z Mp P1-2. Bolniki, okuženi s P1-2, ki so bili starejši od pet let, so imeli višje kazalce vnetja in so pogosteje potrebovali bolnišnično obravnavo. Dodatno smo primerjali podatke bolnikov z okužbo spodnjih dihal s tremi najpogostejšimi genotipi MLVA, in sicer MLVA-3,5,6,2, MLVA-3,6,6,2 in MLVA-4,5,7,2. Vnetni kazalci so bili pomembno višji pri bolnikih, starejših od pet let, okuženih z MLVA-3,5,6,2. Bolnišnično obravnavo zaradi izpuščaja so pogosteje potrebovali mlajši otroci, okuženi s sevom MLVA-3,6,6,2. Z uporabo modela logistične regresije smo opredelili, da imajo pri obravnavi otroka s sumom na atipično pljučnico starost, trajanje simptomov in spremembe na RTG p.c. najvišjo napovedno vrednost za mikoplazemsko okužbo spodnjih dihal. Zaključki: V naši raziskavi nismo potrdili povezave genotipa Mp P1 in MLVA z določeno pljučno ali izvenpljučno klinično sliko. Kljub temu pa rezultati naše velike kohortne raziskave kažejo na to, da so verjetno različni genotipi Mp različno virulentni, saj so imele okužbe spodnjih dihal in kožne bolezni, povzročene z določenimi Mp genotipi, težji potek. Vpliv genotipa Mp na kazalce resnosti bolezni smo opredelili predvsem pri otrocih, starejših od pet let.

Language:Slovenian
Keywords:Mycoplasma pneumoniae, genotip, okužbe dihal, izvenpljučne okužbe, otroci
Work type:Doctoral dissertation
Organization:MF - Faculty of Medicine
Year:2024
PID:20.500.12556/RUL-154579 This link opens in a new window
Publication date in RUL:22.02.2024
Views:162
Downloads:9
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Secondary language

Language:English
Title:​The impact of Mycoplasma pneumoniae genotypes on clinical characteristics of infection in children
Abstract:
Background and aim: Mycoplasma pneumoniae (Mp) is a common cause of lower respiratory tract infections (LRTI) in children. Nevertheless, it can also cause several extrapulmonary manifestations. Factors determining clinical outcome and clinical severity of Mp infections are only partly understood. Mp strains can be classified into two genetic groups called P1 type 1 (P1-1) and P1 type 2 (P1-2) based on the DNA sequence of the P1 adhesion protein gene. Multiple-Locus Variable number tandem repeat Analysis (MLVA) offers a more discriminative categorization of strains. It is mainly unknown if Mp genotype is associated with the clinical outcome of Mp infections in children. By investigating clinical features of patients with an acute Mp infection, we aimed to determine if Mp genotype is associated with the presentation and severity of acute infection in children. Methods: We performed a retrospective study of children referred to University Children’s Hospital Ljubljana and Department of Infectious Diseases Ljubljana with signs of acute Mp infection from January 2014 to December 2014. All patients 䁤18 years who were PCR-positive for Mp from pharyngeal swabs were recruited for the study. We excluded patients who did not show signs of acute infection and cases where additional testing provided evidence that other infectious or non-infectious agents were the more likely cause of the disease. The patients were further divided into groups according to clinical outcome and Mp P1 and MLVA genotype. Firstly, we assessed the association between Mp P1 and MLVA genotype and a specific clinical outcome. Secondly, we compared epidemiological and clinical data of patients with LRTI, infected with either P1-1 or P1-2, and between the most frequent MLVA strains. Thirdly, we compared epidemiological and clinical data of patients with cutaneous disease, infected with either P1-1 or P1-2, and between the most frequent MLVA strains. Lastly, the characteristics of patients with PCR-positive Mp infection were compared to those of patients who tested PCR-negative for Mp. Results: In the study period, 1621 children were referred to our hospitals with signs of acute Mp infection. After applying the inclusion and exclusion study criteria, we evaluated data from 482 patients (260 (54 %) boys and 222 girls (46 %), mean age 6,9 years; standard deviation (SD) 3,4 years). The most frequent clinical outcome in our patients were LRTI, observed in 88 % of cases (425/482). Thirteen percent of children (62/482) presented with an extrapulmonary clinical outcome. Of those, cutaneous disease was the most frequent, observed in 9 % of cases (45/482). We found no association between Mp genotype and a specific pulmonary and extrapulmonary clinical outcome in our sample of patients with acute Mp infection. Data from 310 patients with LRTI infected with P1-1 were compared with 110 patients infected with P1-2. P1-2-infected children over five years presented with significantly higher inflammatory marker levels and were admitted to the hospital more often. In addition, we compared the data of patients with LRTI infected with the three most common MLVA types: MLVA-3,5,6,2, MLVA-3,6,6,2, and MLVA-4,5,7,2. MLVA-3,5,6,2-infected patients older than five years presented with significantly higher inflammatory marker levels than MLVA-3,6,6,2- and MLVA-4,5,7,2-infected patients. Infections with MLVA-3,6,6,2 strains were more frequent in admitted patients with cutaneous disease compared to other MLVA strains. Age, duration of symptoms, and chest radiographic findings had the highest predictive value for Mp LRTI in a multivariable logistic regression model. Conclusions: In our research we found no association between Mp P1 and MLVA genotype and a specific pulmonary and extrapulmonary clinical outcome. However, the results from our large cohort indicate that Mp genotypes may have different pathogenic potentials, which was especially observed when comparing markers of disease severity of patients with LRTI and cutaneous disease older than five years.

Keywords:Mycoplasma pneumoniae, genotype, respiratory tract infection, extrapulmonary manifestation, children

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