Risk of Rotavirus Vaccination for Children with SCID

Abstract

To the Editors: Quinn et al.1 demonstrated reduced morbidity and mortality from acute gastroenteritis by rotavirus vaccination in young children in Australia. We agree with the consensus statement highlighting these benefits in both developed and developing settings, which clearly outweigh the small increased risk of intussusception.2 Nevertheless, we think that the additional risk rotavirus vaccination poses for children with severe combined immunodeficiency (SCID) needs comment. Recently, we saw a 21-month-old boy from a country in the Middle-East who was in reduced general condition for further diagnosis and management at our center. Although his older brother died at 20 months of age suffering from postvaccinational BCGitis and severe cytomegalovirus infection, our patient had received rotavirus vaccine (Rotarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) twice at 3 and 4 months of age. Ever since, he suffered from chronic gastroenteritis, which resulted in severe stunting and wasting. The patient had a x-linked hemizygous mutation in Exon 2 of the IL2RG gene (c.252C>A, p.Asn84Lys; MIM# 300400) and curative therapy with stem cell transplantation was initiated at our specialized medical center.3 We identified rotavirus vaccine strain in stool samples by sequencing of 8 different gene segments (VP1, VP2, VP4, VP6, VP7, NSP2, NSP4 and NSP5). In all segments vaccine-associated sequences harboring few new mutations were found, leading to the conclusion that the child’s chronic gastroenteritis was caused by persisting infection with the vaccine rotavirus strain (see Table, Supplemental Digital Content 1, https://links.lww.com/INF/B978). No other pathogen could be identified in multiple stool samples, including uncommon parasites, coccidia and helminths. Notably, all stool, blood and respiratory specimens were also tested by Luminex xTAG respiratory and xTAG gastrointestinal pathogen panel (Abbott Molecular, Wiesbaden, Germany). In samples from the respiratory tract, we detected high copy numbers of human bocavirus (HBoV) and rhinovirus, which most likely subsequently caused respiratory failure in our patient. Despite all intensive supportive care and treatment, the boy’s condition deteriorated and he died on day 1 after stem cell transplantation. In addition to the association with intussusception, shedding of rotavirus for a period of time after oral vaccination and vaccine-induced severe gastroenteritis including infection of healthy siblings have been reported.4 The observation of acute and chronic infections by vaccine strain rotavirus in immunocompromised children led to the addition of SCID as contraindication for administration of rotavirus vaccine.5–7 Our SCID patient presented already with advanced disease and severely reduced general condition. We believe that viral shedding of rotavirus for such a prolonged period of time has not been previously reported and might be explained by the lack of timely adequate medical management. We cannot completely exclude that other gastrointestinal infections and other comorbidities might have been involved, but we propose that vaccine-acquired rotavirus-infection had probably contributed significantly to the fatal outcome. The clinical manifestation and diagnosis of SCID patients might be delayed well into the life period after the recommended vaccination schedule. Therefore, we emphasize the negative effect that rotavirus vaccination might have in these endangered patients and we strongly support efforts of mandatory newborn screening for SCID.8TABLE 1: Comparison of Rotavirus Sequences From Patient Sample and Vaccine StrainDennis Klinkenberg, MD Martin Blohm, MD Department of Paediatrics University Medical Center Hamburg-Eppendorf Hamburg, Germany Marina Hoehne, PhD Andreas Mas Marques, PhD Robert-Koch-Institute Berlin, Germany Monika Malecki, PhD Kliniken der Stadt Köln gGmbH Institut für Hygiene Köln-Merheim, Germany Verena Schildgen, PhD Klinken der Stadt Köln gGmbH Institut für Pathologie Furth, Germany Reinhard Schneppenheim, MD, PhD Ingo Müller, MD, MSc Department for Paediatric Haematolog and Oncology University Medical Center Hamburg-Eppendorf Bone Marrow Transplantation Unit Hamburg, Germany Oliver Schildgen, PhD Klinken der Stadt Köln gGmbH Institut für Pathologie Furth, Germany Robin Kobbe, MD Department of Paediatrics University Medical Center Hamburg-Eppendorf Hamburg, Germany