Toksoplazmoza je česta ali kod pacijenata lečenih transplantacijom uglavnom zanemarena i pogrešno
dijagnostikovana oportunistička infekcija koja može ugroziti engraftment ali može i evoluirati u
životno ugrožavajuću diseminovanu infekciju. Nakon transplantacije, infekcija parazitom Toxoplasma
gondii se može razviti kao reaktivacija hronične infekcije ili može biti preneta graftom.
Naša osmogodišnja prospektivna studija bila je usmerena na dijagnostiku i monitoring toksoplazmatske
infekcije (TI) kod primalaca matičnih ćelija hematopoeze (haematopoietic stem cell
transplant, HSCT) u centru koji primenjuje protokol uzdržavanja od profilakse do engraftmenta, i
kod primalaca transplantata srca (heart transplant, HT) koji su na kontinuiranoj profilaksi trimetoprim-
sulfametoksazolom (TMP-SMX).
Cilj nam je bio utvrđivanje incidence TI u ova dva vrlo različita transplantaciona režima, i to pre nego
što evoluira u klinički manifestnu, potencijalno fatalnu bolest (Toxoplasma disease, TD). Pre-transplantacioni
serološki i qPCR skrining u post-transplantacionom toku zamenjen je redovnim qPCR
monitoringom iz uzoraka periferne krvi (peripheral blood, PB) usmerenim na Toxoplasma 529 bp gen. Kod primalaca HSCT, qPCR je rađen jednom nedeljno dok je kod primalaca HT qPCR rađen jednom
mesečno prva dva meseca post-HT i potom jednom godišnje. TI je dijagnostikovana na bazi
pozitivnog PCR rezultata iz bar jednog uzorka PB. TI je dijagnostikovana kod 21/104 (20.2%) primalaca
HSCT, prevashodno nakon alogene (19/75) i retko nakon autologne HSCT (2/29). Više od
50% slučajeva TI dijagnostikovano je tokom prvog meseca post-HSCT, pre engraftmenta odnosno
tokom uzdržavanja od profilakse. Sa druge strane, TI je dijagnostikovana kod 3/37 (8.1%) primalaca
HT. Uprkos primeni TMP-SMX, qPCR je postao pozitivan godinu dana posle HT kod dva i dve godine
post-HSCT kod trećeg pacijenta. Infekcija je bila preneta graftom kod 2/3 (seronegativni) a reaktivirana
kod 1/3 primalaca HT (seropozitivni primalac HT poreklom od seropozitivnog donora).
Naši rezultati potvrđuju da je sistemski qPCR monitoring iz uzoraka PB dragocen u dijagnostici TI
ne samo kod primalaca HSCT već i kod primalaca solidnih organa, posebno nakon HT. Učestalost
qPCR monitoringa se mora adaptirati shodno specifičnostima transplantacionog protokola, pre
svega primeni profilakse ali i osnovnoj dijagnozi, na način koji omogućava pravovremenu primenu
specifične terapije u svakom slučaju TI.Toxoplasmosis is a common but often neglected and misdiagnosed opportunistic infection in transplant
recipients, which can not only compromise the engraftment, but also evolve into life-threatening
disseminated infection. Post-transplantation, Toxoplasma gondii infection can develop as a reactivation
of chronic infection or could be graft-transmitted. We conducted an eight-year-long prospective
study on the diagnosis and monitoring of Toxoplasma infection (TI) in haematopoietic stem cell
transplant (HSCT) recipients in a setting that withholds prophylaxis until engraftment, and in heart
transplant (HT) recipients on continuous trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis.
The objective was to determine the incidence of TI before it evolves into clinical, potentially fatal
Toxoplasma disease (TD), in these two very different transplantation settings. Pre-transplantation
serological and qPCR screening was followed by post-transplantation peripheral blood (PB)-based
qPCR monitoring targeting the Toxoplasma 529 bp gene. In HSCT recipients, qPCR was performed
weekly while in HT recipients, qPCR was performed monthly for two months post-HT and then
yearly. TI was diagnosed based on a positive PCR result in at least one PB sample.
TI was diagnosed in 21/104 (20.2%) HSCT recipients, predominantly after allogeneic (19/75) and
rarely after autologous HSCT (2/29). Over 50% of TI cases were diagnosed during the first month
post-HSCT, while awaiting engraftment without prophylaxis. On the other hand, TI was diagnosed
in 3/37 (8.1%) HT recipients. Regardless of the TMP-SMX prophylaxis, qPCR became positive one
year after HT in two and two years post-HSCT in third patient. Infection was graft-transmitted in 2/3
(seronegative) and reactivated in 1/3 OHT (seropositive recipient of a seropositive donor’s heart
transplant).
The presented results show that systematic PB-based qPCR monitoring is a valuable resource for
the diagnosis of TI not only in HSCT but also in solid organ recipients, especially after HT. Frequency
of qPCR monitoring should be adjusted according to the specificity of the transplantation setting,
especially in terms of prophylaxis but also an underlying diagnosis, in a manner allowing for prompt
introduction of specific treatment in each case of TI