Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant

Abstract

Background: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection.

Methods: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays.

Results: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%).

Conclusions: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.

Keywords: Children; Diarrhea; Hematopoietic stem cell transplantation; Multiplexed polymerase chain reaction.

Fig. 1

Flowchart of patient recruitment. A total of 158 patients were recruited from 175 patients undergoing HSCT during the study period. Eighty-four of the 158 patients experienced diarrhea episodes after transplantation, while the other 74 patients did not. HSCT hematopoietic stem cell transplantation

Fig. 2

Etiologies of diarrhea after transplantation. a Etiologies of diarrhea in 84 patients who experienced diarrhea episodes after transplantation; b etiologies of diarrhea that combined all factors, including infection, GVHD and medication; c the incidence of diarrhea and infectious diarrhea in colonized and non-colonized patients. GVHD graft-versus-host disease

Fig. 3

Pathogens detected by FilmArray gastrointestinal (GI) panel in pre- and post-transplantation stool samples. The number of patients who had a clinically relevant post-transplantation diarrheal infection due to pre-transplantation colonization is shown for each pathogen (red part in the bar plot). EPEC enteropathogenic Escherichia coli, EAEC enteroaggregative E. coli, ETEC enterotoxigenic E. coli

Fig. 4

Impact of different underlying diseases on pathogen colonization and subsequent development of infectious diarrhea due to the colonized pathogens. a The number and proportions of patients with different underlying diseases who were colonized with gastrointestinal pathogens pre-transplantation; b the number and proportions of patients in the colonized group who developed infectious diarrhea due to their colonized pathogens. HM hematological malignancies, PI primary immunodeficiency, AA aplastic anemia, IMD inherited metabolic disorders