Prospective Weekly Surveillance Of Respiratory Viruses Using Viral Culture In First 100 Days After Allogeneic Stem Cell Transplantation
Authors: Tsuji Masanori , Kakiuchi Satsuki , Nishimura Hidekazu , Ota Hikari , Nishida Aya , Ishiwata Kazuya , Araoka Hideki , Yamamoto Hisashi , Asano-Mori Yuki , Uchida Naoyuki , Izutsu Koji , Wake Atsushi , Makino Shigeyoshi , Yoneyama Akiko , Lim Chang-Kweng , Saijo Masayuki , Taniguchi Shuichi 
Published: October 2019

Abstract

Background
Respiratory viral infections (RVI) in early phase after allogeneic stem cell transplantation (alloSCT) are associated with high morbidity and mortality and may result in institutional outbreak. So far, there have been few reports on incidence of RVI in alloSCT recipients with prospective surveillance.

Methods
We prospectively surveyed 247 recipients (271 transplants)who received alloSCT in Toranomon Hospital from June 2010 to May 2012. Oropharyngeal swab samples were collected weekly from each patient starting from 1 week before transplantation until 100 days after SCT. Respiratory viruses (RV) were isolated by viral culture (HHMV method). Symptoms related to RVI including fever, cough, sputum, and rhinorrhea were surveyed with patient questionnaire form. To exclude concomitant infection, culture of sputum and blood, serological tests (such as Aspergillus-galactomannan and beta-D-glucan), antigen test of influenza (Flu) and PCR of respiratory syncytial virus (RSV), parainfluenzavirus (PIV) type 3, and adenovirus (ADV) were routinely performed in symptomatic patients. RVI was defined by detection of RV from viral culture. Respiratory viral infectious disease (RVID) was defined as fulfilling both the definition of RVI and the presence of at least one of respiratory symptoms except for fever. In patients with RVID, chest X-ray and/or computed tomography were performed for the diagnosis of upper (URTID) or lower respiratory tract infectious disease (LRTID).

Results
One hundred and seventy-seven patients (65.3%) developed respiratory symptoms in first 100 days after alloSCT and RVs were detected from 59 patients (24.1%); PIV3 was detected in 49 patients, PIV2 in 3, PIV1 in 1, RSV in 2, FluA in 2, ADV in 1, and mumps virus in 1. There were no culture-positive patients without any symptoms. RVs were detected by PCR and antigen test from 25 culture-negative patients with respiratory symptoms; RSV was detected in 10 patients, PIV3 in 9, FluA in 1, RSV and PIV3 in 1, and PIV3 and ADV in 2. RSV was less detected by viral culture compared to PCR. All patients with RVI developed respiratory symptoms (median days of onset: 15.5 days), and symptoms presented before the detection of RVs in all of them. Radiological findings showed LRTID in 40 patients with RVI. Respiratory symptoms were improved in 39 of patients with RVI and the median duration from onset to cure of their RVID was 26 days (7-115). Although a majority of RVID was self-limited, seven patients (12.1%) died from RV-induced LRTID. Two of them developed interstitial pneumonia without other pathogens, and 5 of them had co-infection with other pathogens; Aspergillus spp. was detected in 1 patient, Pseudomonas aeruginosa in 1, Stenotrophomonas maltophilia in 1, and other RVs in 2 (RSV 1 and ADV 1) only detected by PCR. Six died patients developed RVI-induced LRTID before engraftment. Viral shedding occurred from 1 to 4 weeks (median: 1 week). Phylogenetic analysis of hemagglutinin-neuraminidase genes revealed institutional outbreak of PIV3 in 3 seasons (summer and winter in 2010, summer in 2011).

Conclusion
This study showed the high frequency of RV infections in early phase after alloSCT and horizontal dissemination of PIV3 in transplantation unit confirmed by genetical method. Although a majority of RVID was self-limited, patients who developed RVID before engraftment and had concomitant pulmonary infection were sometimes fatal. Thorough prophylactic strategy for respiratory viruses including early precise detection and patient isolation should be necessary to reduce the rate of RVI-induced mortality and to prevent outbreaks by RV.

Disclosures:
No relevant conflicts of interest to declare.