Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation

Kourí et al. SpringerPlus 2014, 3:247 http://www.springerplus.com/content/3/1/247 RESEARCH a SpringerOpen Journal Open Access Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation Vivian Kourí1,8*†, Consuelo Correa1†, Pedro A Martínez1, Lizet Sanchez2, Alina Alvarez1, Grehete González6, César E Silverio3, Norma Hondal3, Jose Florin4, Lourdes Pérez4, Diana P Duran4, Yardelis Perez4, Nancy Cazorla4, Dalmaris Gonzalez4, Juan C Jaime5, Alberto Arencibia5, Sandra Sarduy5, Lissette Pérez1, Yudira Soto1, Mabel González3, Iliana Alvarez3, Elvira Dorticós5, Juan J Marchena4, Luis Solar4, Belsy Acosta6, Clara Savón6 and Ulrich Hengge7 Abstract Purpose: In Cuba, viral monitoring in the post-transplant period was not routinely performed. The aim of this research is to identify the most frequent viruses that affect transplanted Cuban children, by implementing a viral follow-up during the post-transplant period. Methods: The study population included all Cuban pediatric patients who underwent solid organ transplantation (SOT) between November 2009 and December 2012. A total of 34 transplanted pediatric patients of kidney (n = 11) and liver (n = 23) were prospectively monitored during a 34-week period for viral DNAemia and DNAuria by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus, herpes simplex virus type 1 and 2, varicella zoster virus, human herpesvirus 6, human adenovirus, and polyomaviruses (BKV and JCV) using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Viral genome of at least one virus was detected in 21 of 34 recipients, 18 patients excreted virus in urine while 12 presented DNAemia. CMV (41.2%) and BKV (35.3%) were the most frequent viruses detected during the follow-up. CMV was the virus mainly associated with clinical symptoms and DNAemia. Its excretion in urine (with cut off value of 219 copies/mL) was associated with detection in plasma (p < 0.001); furthermore, CMV viruria was predictive of CMV viremia (OR:8.4, CI:2.4-29.1, p = 0.001). There was no association between high viral load and clinical complications, due to the prompt initiation of preemptive ganciclovir. Conclusion: This comprehensive viral monitoring program effectively prevents the development of critical viral disease, thus urge the implementation of qRT-PCR as routine for viral monitoring of transplanted Cuban organ recipients. Keywords: Transplant; Pediatric; CMV; Cuba; Viruses Background Infections represent one of the most frequent complications among patients undergoing organ transplantation, and among them viral infections constitute a significant cause of morbidity and mortality after solid organ transplantation (SOT). They not only induce specific diseases, * Correspondence: † Equal contributors 1 Sexually Transmitted Diseases Laboratory, Virology Department, Institute of Tropical Medicine “Pedro Kourí”, Havana City, Cuba 8 Virology Department, Institute of Tropical Medicine ¨Pedro Kourí¨, Autopista Novia del Mediodia Km 6., La Lisa, Havana City, Cuba Full list of author information is available at the end of the article but also favor the development of allograft damage, opportunistic infections, and acute rejection (Fishman and Rubin, 1998). Although cytomegalovirus (CMV) is the most common opportunistic pathogen seen in transplant recipients, other viruses may also affect clinical outcome. Among them, other herpesviruses, polyomaviruses and adenoviruses are important (Imperiale and Major, 2007; Rickinson and Kieff, 2007; Roizman et al., 2007; Wold and Horwitz, 2007; Yamanishi et al., 2007). Major advances in the management of all these viral infections have been achieved because of the availability of novel pharmaceutical agents. In addition, the establishment © 2014 Kourí et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Kourí et al. SpringerPlus 2014, 3:247 http://www.springerplus.com/content/3/1/247 Page 2 of 9 of polymerase chain reaction (PCR)-based qualitative and quantitative (qRT-PCR) monitoring of viral DNA in blood or serum (DNAemia) has allowed optimal management of antiviral treatment in many countries, as it permits the identification of preclinical or early stages of virus-related pathology (Humar and Michaels, 2006; Martin-Gandul et al., 2013). However, the appropriate extent of viral monitoring and the critical time window for initiating PCR-guided preemptive antiviral therapy remain controversial. Recent studies on the screening and management of viral infections have focused on CMV, and comprehensive data on viral DNAemia and disease, including CMV and other relevant viruses in the post-transplantation settings, such as Epstein-Barr virus (EBV), herpes simplex virus (HSV), human herpesvirus 6 (HHV6), human adenovirus (ADV), and BK virus (BKV), are sparse. In addition, most previous studies predominantly analyzed adult transplantation cohorts (Schonberger et al., 2010). The pediatric cohort is at high risk of developing virus-related complications due to immunological immaturity and the increased alloreactivity risk that requires a strong immunosuppressive treatment (Grimaldi et al., 2005). In 1970, Cuba initiated the transplantation program. Currently, kidney and liver are the more common organ transplants performed in children (Abdo Cuza 2010). However, only serological pre-transplant screening is carried out, whereas specific viral tests (qualitative PCR) are requested when clinical signs and symptoms, suggestive of viral disease, appear. Furthermore, neither quantitative methods for monitoring of viral infections nor preemptive therapy have ever been used in this group of patients. The aim of this research is to identify the most frequent viruses that affect Cuban transplanted children, by implementing an appropriate viral follow-up during the post-transplant period. Results As shown in Table 1, 29 out of the 34 (85.3%) transplanted patients survived after the graft and 25 (73.5%) successfully completed the follow-up, with best results observed for patients with liver transplantation (82.6%, 19/23 patients). Unfortunately, 14.7% of patients died immediately or few days post-transplantation (average 25 days, range 8–48 days), mainly by complications directly linked to the surgery or due to the low Karnofsky performance status at the time of transplantation (Schag et al., 1984; Yates et al., Table 1 General information of the transplanted patients studied Patients characteristics Donor* n(%) Live (%) Total of patients n = 34 (100%) Liver n = 23 (100%) Kidney n = 11 (100%) 5 (14.7) 4 (17.4) 1 (9.1) 19 (82.6) 10 (90.9) Age average average of years (range) Deceased (%) 29 (85.3) 10.4 (1–17) 9.6 ( (...truncated)