Clive Taylor

Environmental Monitoring for Gastroenteric Viruses in a Pediatric Primary Immunodeficiency Unit

ABSTRACT The aim of this study was to determine if gastroenteric viruses were present on surfaces and equipment in a pediatric primary immunodeficiency unit (PPIU) by environmental sampling using swabs and subsequent nucleic acid extraction and reverse transcriptase PCR assays. A PPIU was chosen, and 11 swabs were taken at the same sites every 2 weeks for 6 months. Nested/heminested PCR assays were used to screen for astroviruses (AsV), noroviruses (NoV), and rotaviruses (RV). AsV, NoV, and RV were detected at multiple swab sites during the study period. NoV was the most frequently detected virus on environmental surfaces; however, RV was detected on 79% and NoV on 50% of swabbing dates during the study period. Toilet taps were the most contaminated sites. Fecal samples from selected patients in the unit were also screened during the study period, and patients excreted AsV, NoV, and RV at times during the study. New cleaning schedules and changes in some of the PPIU sanitary furniture have been suggested as a means of reducing environmental contamination.

Contamination of the Hospital Environment with Gastroenteric Viruses: Comparison of Two Pediatric Wards over a Winter Season

ABSTRACT The aims of this study were to examine the extent of gastroenteric virus contamination in a pediatric primary immunodeficiency (PPI) ward and a general pediatric ward over a winter season and to determine whether changes to hospital infection control interventions would have an impact on environmental contamination levels within pediatric units. Environmental swabs were collected weekly from 11 sites in both wards from 15 December 2005 to 3 March 2006 and examined for the presence of norovirus (NoV), astrovirus, and rotavirus (RV) by reverse transcriptase PCR. Viruses were detected in 17% and 19% of swabs from both wards. Virus contamination for NoV and RV decreased from 20% to 6% and 15% to 10% of swabs, respectively, in the PPI ward from the 2004 study by Gallimore et al. (C. I. Gallimore, C. Taylor, A. R. Gennery, A. J. Cant, A. Galloway, M. Iturriza-Gomara, and J. J. Gray, J. Clin. Microbiol. 44:395-399, 2006). Overall, changes to cleaning protocols were deemed to have reduced the level of environmental contamination with gastroenteric viruses, but contamination still occurred due to a breakdown in infection control procedures indicated by contamination in areas frequented by parents but used only occasionally by staff.

Prevention and management of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation - a systematic review and evidence-based guidance for clinical management

Haemorrhagic cystitis (HC) is a common and, in its severe form, potentially life‐threatening complication of Haematopoietic stem cell transplantation (HSCT) in children. Recent data indicate an important role of BK virus reactivation during the time of maximal post‐transplant immune suppression in the pathogenesis of late‐onset HC. Treatment of HC is mainly symptomatic and often frustrating. To give clinicians guidance on prevention and treatment options and their backing by scientific evidence, we have systematically assessed the available literature and devised evidence‐based guidelines. Our comprehensive review demonstrates that evidence for the most commonly used interventions (such as cidofovir, oestrogen, hyperbaric oxygen, bladder instillation with formalin, alum salts or prostaglandin) is very limited. Some of these interventions also carry significant risks. Higher level evidence exists only for 2‐mercaptoethane sodium (MESNA) and hyperhydration as a preventative intervention, and for systemic recombinant Factor VII as a treatment to stop acute haemorrhage. Further high‐quality studies are required to establish effective and safe prevention and treatment options for HC.

Adenovirus Type F Subtype 41 Causing Disseminated Disease following Bone Marrow Transplantation for Immunodeficiency

ABSTRACT Adenovirus causes disseminated disease following bone marrow transplantation (BMT). We report a child who underwent T-cell-depleted BMT. Adenovirus subgenus F serotype 41 was detected antemortem by PCR in cerebrospinal fluid and postmortem in other tissues. Serotypes 40 and 41, associated with gastrointestinal disease, have not previously been implicated in disseminated disease.

LightCycler-Based Quantitative PCR for Rapid Detection of Human Herpesvirus 6 DNA in Clinical Material

Locatelli et al. ([6][1]) reported on the quantitative detection of human herpesvirus 6 (HHV-6) in plasma and cell suspensions by TaqMan-based PCR. We wish to add our experience. We have developed a rapid (<30-min) assay for the simultaneous detection, quantification, and differentiation of HHV-6

Outcome of hematopoietic stem cell transplantation in severe combined immune deficiency with central nervous system viral infection.

Background: Patients with severe combined immunodeficiency and preexisting viral pneumonitis formally had a poor outcome from hematopoietic stem cell transplantation. With inhaled steroid and antitumor necrosis factor α antibody treatment, results improved. The poor outcome of patients with viral central nervous system infection prompted this retrospective single center review. Results: Eight of 71 patients with severe combined immunodeficiency transplanted since 1987 were identified with viral central nervous system infection (adenovirus [1], cytomegalovirus [2], Epstein-Barr virus [2], parvovirus [1], varicella zoster virus [1], human herpesvirus 6 [1]). Nonspecific neurologic symptoms included drowsiness, irritability, head lag, fisting and floppiness. Later symptoms included unresponsiveness, apnea, posturing, hypotonia, hyperreflexia and seizures. All had neuroradiologic investigations. Only one had an initially normal computed tomography scan. Magnetic resonance image abnormalities included cerebral atrophy, basal ganglia changes, diffuse leukoencephalopathy, and multifocal mass lesions. Five patients had virus identified from cerebrospinal fluid by polymerase chain reaction and brain tissue examination from 3 patients identified human herpesvirus 6, adenovirus type 41 and varicella zoster virus. Three children remain alive, 2 received replete marrow and one remains untransplanted. Others who received T cell depleted marrow died of neurologic sequelae. Conclusion: Outcome of viral central nervous system infection after hematopoietic stem cell transplantation for severe combined immunodeficiency is poor, particularly associated with T cell depleted marrow.

Value of bronchoalveolar lavage before haematopoietic stem cell transplantation for primary immunodeficiency or autoimmune diseases

Pulmonary infection, often insidious, is frequent in primary immunodeficiency (PID) and acquired immunodeficiency. Pulmonary complications are serious obstacles to success of haematopoietic SCT (HSCT) for these conditions. Bronchoalveolar lavage (BAL) permits identification of lower respiratory tract pathogens that may direct specific treatment and influence prognosis. There are no reports about the utility of pre-HSCT BAL for immunodeficient patients. We prospectively studied the value of ‘routine’ BAL before commencing transplantation in patients undergoing HSCT for severe immunological disease. Routine non-bronchoscopic BAL was performed under general anaesthetic, a few days before commencing pre-HSCT cytoreductive chemotherapy. Patients were categorized as symptomatic or asymptomatic with respect to pulmonary disease or infection. Samples were sent for microbiological processing. Complications arising from the procedure, pathogens isolated and treatments instituted were recorded. Results were available from 69/75 patients transplanted during the study period; 26 (38%) had pathogens identified (six asymptomatic patients), 10 (14.5%) developed complications post-procedure (two asymptomatic patients)—all recovered, 21 had management changes. There was no statistically significant difference in the number of positive isolates from severe combined or other immunodeficient patients, or of symptomatic or asymptomatic patients. Routine non-bronchoscopic BAL is safe in immunodeficient patients about to undergo HSCT, and leads to management changes.

Commentary to "Pediatric hemorrhagic cystitis" by Decker DB, Karam JA, Wilcox DT. J Pediatr Urol 2009;5:254-264 Management of hemorrhagic cystitis in children after hematopoietic stem cell transplantation: Keep it safe

a Supraregional Children‘s Bone Marrow Transplant Unit, Newcastle General Hospital, Westgate Road, Ward 23, Newcastle upon Tyne, Tyne & Wear NE4 6BE, United Kingdom b Specialist Registrar in Paediatric Surgery, Pediatric Surgery Department, Royal Victoria Infirmary, Newcastle General Hospital, Westgate Road, Ward 23, Newcastle upon Tyne, Tyne & Wear NE4 6BE, United Kingdom c Consultant in Paediatric Immunology & Infectious Diseases, Supraregional Children‘s Bone Marrow Transplant Unit, Newcastle General Hospital, Westgate Road, Ward 23, Newcastle upon Tyne, Tyne & Wear NE4 6BE, United Kingdom d Consultant Paediatric Surgeon, Pediatric Surgery Department, Royal Victoria Infirmary, Newcastle General Hospital, Westgate Road, Ward 23, Newcastle upon Tyne, Tyne & Wear NE4 6BE, United Kingdom e Consultant Microbiologist, Health Protection Agency, Newcastle General Hospital, Westgate Road, Ward 23, Newcastle upon Tyne, Tyne & Wear NE4 6BE, United Kingdom

Prolonged detection of viral DNA in blood following life-threatening chickenpox in an immunocompromised child

In the immunocompetent child chickenpox, caused by primary aricella Zoster virus (VZV) infection, is generally a self-limiting ondition, controlled principally by cell-mediated immunity.1 In ontrast, immunocompromised patients may develop a severe disase, including multi-organ involvement and death. Importantly, the diagnosis of VZV infection in immunocomproised patients may be delayed due to an atypical presentation ithout a rash. In such cases diagnosis may require detection of iral DNA in the blood by polymerase chain reaction (PCR). In the mmunocompetent host VZV DNA is not normally detected for ore than two to three weeks following primary infection,2,3 litle however is known about the situation in immunocompromised atients. We present the case of a child in the maintenance phase of herapy for acute lymphoblastic leukaemia who developed lifehreatening VZV infection, with VZV DNA remaining detectable in he blood beyond fifteen months.